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.

Impact of guideline-directed medical therapy on systolic blood pressure and cardiovascular outcomes in patients with heart failure and low blood pressure: A systematic review and meta-analysis.

AIMS: Existing research indicates that patients with heart failure (HF) may have restricted access to guideline-directed medical therapy (GDMT) when their blood pressure (BP) is comparatively low. However, recent clinical trials suggest that HF patients with low BP could still benefit from certain HF medications, which have a minimal impact on BP. This systematic review and meta-analysis was conducted to determine whether this applies to all GDMT. METHODS AND RESULTS: A systematic search of MEDLINE and EMBASE was conducted for studies published from inception to 10 January 2024. Randomized controlled trials were selected if they reported on the longitudinal change of systolic BP (SBP) due to GDMT, or the risks of cardiovascular events in HF patients based on SBP categories. Weighted mean difference (WMD), hazard ratio or relative risk, and corresponding 95% confidence intervals (CI) were pooled for meta-analysis where possible. Data from 20 studies, encompassing information on 84 782 individuals, were analysed. Overall, GDMT is associated with lower SBP (WMD, -2.16; 95% CI -2.86 to -1.46), with no significant difference between baseline low and non-low BP subgroups (interaction p = 0.810). However, SBP of the treatment group increased by 5.8 mmHg from baseline in the low SBP subgroup during follow-up, while it decreased by 4.0 mmHg in the baseline non-low SBP subgroup. GDMT demonstrated similar cardiovascular benefits and risk of hypotension between low and non-low SBP subgroups (interaction p = 0.318 and 0.903, respectively). CONCLUSIONS: Guideline-directed medical therapy is associated with a negligible decrease in SBP, but can provide similar cardiovascular benefits in both low and non-low SBP HF patients, with no significant interaction with SBP as to hypotension. Therefore, GDMT should be initiated and maintained in HF patients with low BP.

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.

Evaluation on the Effect of Ward-Noise Reduction Management Combined with Monitoring-Training-Planning Management Mode in Hospitalized Patients with Heart Failure.

BACKGROUND: Noise from medical institutions such as hospitals usually exceeds the level recommended by the World Health Organization. This study aimed to explore the application effect of ward-noise reduction management combined with monitoring-training-planning (MTP) management mode in hospitalized patients with heart failure. MATERIALS AND METHODS: Among the 168 research objects, 55 patients with heart failure receiving ward-noise reduction management combined with MTP management mode from April 2022 to March 2023 were included in group A, 52 patients with heart failure who underwent MTP management mode from March 2021 to March 2022 were selected as group B, and 61 patients who underwent routine management measures from March 2020 to February 2021 served as the control group. The vital signs, Self-rating Anxiety Scale (SAS) scores, Self-rating Depression Scale (SDS) scores, physical function indices, sleep quality score, and satisfaction degree of patients in the three groups were compared before and after management. RESULTS: After 1 month of management, group A had lower heart rate, diastolic blood pressure, systolic blood pressure, and respiratory rate compared to group B and the control group (P < 0.001). The SAS score, SDS score, and Pittsburgh Sleep Quality Index score after management in group A were lower than those in group B and the control group (P < 0.001). Group A had a higher 6-Minute Walk Distance than group B and the control group (P < 0.001). Group A had a higher satisfaction degree after management compared to group B (P < 0.01) and the control group (P < 0.001). Group A had lower noise level than group B and the control group (P < 0.001), and there was no significant difference in noise level between group B and the control group (P > 0.05). CONCLUSION: Ward-noise reduction management combined with MTP management mode can reduce the noise level in the ward and improve the psychological state and sleep quality of patients with heart failure.

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.

Transcriptomic Analysis of mRNA Expression Profiles in the Microglia of Mouse Brains Infected with Rabies Viruses of Varying Virulence.

Rabies is a lethal encephalitis caused by the rabies virus (RABV) with a fatality rate near 100% after the onset of clinical symptoms in humans and animals. Microglia are resident immune cells in the central nervous system. Few studies have been conducted on the functional role of microglia in RABV infection. Here, we performed a transcriptomic analysis of mRNA expression profiles in the microglia of mouse brains intracerebrally infected with RABV. We successfully isolated single microglial cells from the mouse brains. The survival rate of dissociated microglial cells was 81.91%-96.7%, and the purity was 88.3%. Transcriptomic analysis revealed 22,079 differentially expressed mRNAs identified in the microglia of mouse brains infected with RABV strains (rRC-HL, GX074, and CVS-24) of varying virulence at 4 and 7 days post-infection (dpi) compared to the control group. The numbers of DEGs versus the control at 4 and 7 dpi in mice infected with rRC-HL, GX074, and CVS-24 were 3622 and 4590, 265 and 4901, and 4079 and 6337. The GO enrichment analysis showed that response to stress, response to external stimulus, regulation of response to stimulus, and immune system process were abundant during RABV infection. The KEGG analysis indicated that the Tlr, Tnf, RIG-I, NOD, NF-κB, MAPK, and Jak-STAT signaling pathways were involved in RABV infection at both 4 and 7 dpi. However, some phagocytosis and cell signal transduction processes, such as endocytosis, p53, phospholipase D, and oxidative phosphorylation signaling pathways, were only expressed at 7 dpi. The involvement of the Tnf and Tlr signaling pathways prompted us to construct a protein-protein interaction (PPI) network of these pathways. The PPI revealed 8 DEGs, including Mmp9, Jun, Pik3r1, and Mapk12. Notably, Il-1b interacted with Tnf and Il-6 with combined scores of 0.973 and 0.981, respectively. RABV causes significant changes in mRNA expression profiles in the microglia in mice. 22,079 differentially expressed mRNAs were identified in the microglia of mice infected with RABV strains of varying virulence at 4 and 7 dpi. The DEGs were evaluated using GO, KEGG, and PPI network analysis. Many immune pathways were up-regulated in RABV-infected groups. The findings will help elucidate the microglial molecular mechanisms of cellular metabolism dysregulated by RABV and may provide important information for investigating RABV pathogenesis and therapeutic methods.

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.

Residual coronary artery tree description and lesion EvaluaTion (CatLet) score, clinical variables, and their associations with outcome predictions in patients with acute myocardial infarction.

BACKGROUND: We have recently developed a new Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system. Our preliminary studies have demonstrated its superiority over the the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery (SYNTAX) score with respect to outcome predictions for acute myocardial infarction (AMI) patients. The current study hypothesized that the residual CatLet (rCatLet) score predicts clinical outcomes for AMI patients and that a combination with the three clinical variables (CVs)-age, creatinine, and ejection fraction, will enhance its predicting values. METHODS: The rCatLet score was calculated retrospectively in 308 consecutively enrolled patients with AMI. Primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) including all-cause mortality, non-fatal AMI, transient ischemic attack/stroke, and ischemia-driven repeat revascularization, was stratified according to rCatLet score tertiles: rCatLet_low ≤3, rCatLet_mid 4-11, and rCatLet_top ≥12, respectively. Cross-validation confirmed a reasonably good agreement between the observed and predicted risks. RESULTS: Of 308 patients analyzed, the rates of MACCE, all-cause death, and cardiac death were 20.8%, 18.2%, and 15.3%, respectively. Kaplan-Meier curves for all endpoints showed increasing outcome events with the increasing tertiles of the rCatLet score, with P values <0.001 on trend test. For MACCE, all-cause death, and cardiac death, the area under the curves (AUCs) of the rCatLet score were 0.70 (95% confidence intervals [CI]: 0.63-0.78), 0.69 (95% CI: 0.61-0.77), and 0.71 (95% CI: 0.63-0.79), respectively; the AUCs of the CVs-adjusted rCatLet score models were 0.83 (95% CI: 0.78-0.89), 0.87 (95% CI: 0.82-0.92), and 0.89 (95% CI: 0.84-0.94), respectively. The performance of CVs-adjusted rCatLet score was significantly better than the stand-alone rCatLet score in terms of outcome predictions. CONCLUSION: The rCatLet score has a predicting value for clinical outcomes for AMI patients and the incorporation of the three CVs into the rCatLet score will enhance its predicting ability. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR-POC-17013536.

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.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS: Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS: In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS: Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04179669.