RESUMEN
Curcumin has demonstrated promising preclinical antiobesity effects, but its low bioavailability makes it difficult to exert its full effect at a suitable dose. The objective of this study was to screen curcumin derivatives with enhanced bioavailability and lipid-lowering activity under the guidance of computer-aided drug design (CADD). CAAD was used to perform virtual assays on curcumin derivatives to assess their pharmacokinetic properties and effects on pancreatic lipase activity. Subsequently, 19 curcumin derivatives containing 5 skeletons were synthesized to confirm the above virtual assay. The in vitro pancreatic lipase inhibition assay was employed to determine the half-maximal inhibitory concentration (IC50) of these 19 curcumin derivatives. Based on CADD analysis and in vitro pancreatic lipase inhibition, 2 curcumin derivatives outperformed curcumin in both aspects. Microscale thermophoresis (MST) experiments were employed to assess the binding equilibrium constants (K d) of the aforementioned 2 curcumin derivatives, curcumin, and the positive control drug with pancreatic lipase. Through virtual screening utilizing a chemoinformatics database and molecular docking, 6 derivatives of curcumin demonstrated superior solubility, absorption, and pancreatic lipase inhibitory activity compared to curcumin. The IC50 value for 1,7-bis(4-hydroxyphenyl)heptane-3,5-dione (C4), which displayed the most effective inhibitory effect, was 42.83 µM, while the IC50 value for 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (C6) was 98.62 µM. On the other hand, the IC50 value for curcumin was 142.24 µM. The MST experiment results indicated that the K d values of C4, C6, and curcumin were 2.91, 18.20, and 23.53 µM, respectively. The results of the activity assays exhibited a relatively high degree of concordance with the outcomes yielded by CADD screening. Under the guidance of CADD, the targeted screening of curcumin derivatives with excellent properties in this study exhibited high-efficiency and low-cost benefits.
RESUMEN
Purpose: The association between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and cardiovascular risk in patients with coronary artery disease remains inconsistent. Recent investigations indicated potential dysfunctionality of HDL under inflammation. This study endeavors to explore whether the inflammatory status modifies the effects of HDL-C and ApoA-I on cardiovascular risk in individuals with percutaneous coronary intervention (PCI). Patients and Methods: Consecutive 10,724 PCI patients at Fuwai hospital in 2013 were enrolled. Inflammation status was defined by high-sensitivity C-reactive proteins (hsCRP) ≥ 2 mg/L. The study endpoint was cardiac mortality. Results: Among 9569 PCI patients eventually included, 225 (2.4%) cardiac mortality happened during 5 years. In hsCRP ≥ 2 mg/L group, an U-shaped curve was observed for HDL-C and multivariate Cox regression showed that elevated risks of cardiac mortality correlated to both the lowest quintile (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.32-4.71) and the highest quintile of HDL-C (HR, 2.28; 95% CI, 1.23-4.25). However, an L-shaped curve existed in ApoA-I, indicating only the lowest quintile level of ApoA-I was associated with an increased cardiac mortality risk (HR, 2.19; 95% CI, 1.28-3.75). Nevertheless, in hsCRP < 2 mg/L group, no significant correlations between HDL-C and ApoA-I and cardiac mortality risk were identified (both P > 0.05). Conclusion: In PCI patients with hsCRP ≥ 2 mg/L. both low and high HDL-C levels correlated with higher cardiac mortality risk (U-shaped), while only low ApoA-I levels were linked to elevated risk (L-shaped). However, in patients with hsCRP < 2 mg/L, neither HDL-C nor ApoA-I levels were associated with higher cardiac mortality risk. These findings shed light on the importance of considering inflammation status, particularly hsCRP levels, in managing HDL-C and ApoA-I levels, and suggest targeting elevated ApoA-I levels as a potential therapeutic approach for PCI patients with hsCRP ≥ 2 mg/L.
RESUMEN
The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.
RESUMEN
Aim: The information assessing sex differences in outcomes of patients with three-vessel coronary disease (TVD) after different treatment strategies is sparse. This study aimed to investigate long-term outcomes of TVD among women compared with men after medical therapy (MT) alone, percutaneous coronary intervention (PCI), or coronary artery bypass grafting surgery (CABG). Methods: Consecutive 8943 patients with TVD were enrolled. Associations between sex and all-cause death and major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, myocardial infarction, or stroke) were assessed. Results: Of the 8943 patients, 1821 (20.4%) were women. During a median follow-up of 6.6 years, women had comparable incidences of all-cause death (16.6% vs. 14.9%, P = 0.079) and MACCE (27.2% vs. 26.1%, P = 0.320) to men. After multivariable analysis, women showed lower adjusted risks of all-cause death (HR: 0.777; P = 0.001) and MACCE (HR: 0.870; P = 0.016) than men in the entire cohort. Subgroup analysis revealed that the less all-cause death risk of women relative to men was significant in PCI (HR: 0.702; P = 0.009), and CABG groups (HR: 0.708; P = 0.047), but not in MT alone group. Lower MACCE risk for women vs. men was significant only in PCI group (HR: 0.821; P = 0.037). However, no significant interaction between sex and three strategies was observed for all-cause death (P for interaction = 0.312) or MACCE (P for interaction = 0.228). Conclusions: The cardiovascular prognosis of TVD female patients is better than that of men, which has no interaction with the treatment strategies received (MT alone, PCI, or CABG).
Asunto(s)
Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Femenino , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/terapia , Factores Sexuales , Puente de Arteria Coronaria/estadística & datos numéricos , Anciano , Estudios de Seguimiento , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Incidencia , Causas de Muerte/tendencias , Factores de Riesgo , Tasa de Supervivencia/tendenciasRESUMEN
OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.
Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Terapia Neoadyuvante/métodos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/mortalidad , Anciano , Inmunoterapia/métodos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
The Balanophorae are not only traditional Chinese herbal medicines but also functional foods with diverse sources. This study aimed to distinguish pharmacognostic characteristics and secondary metabolites among different species of Balanophorae. Eight species of Balanophorae herbs were harvested, including 21 batches with 209 samples. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze secondary metabolites of Balanophorae from 21 sources. Targeted metabolomic analysis was performed to compare differences among the groups. Rhopalocnemis phalloide and B. indica can be identified by their pharmacognostic characteristics. Then, 41 secondary metabolites were identified or characterized in the mixed extracts of the 209 samples, mainly phenolic acids, flavonoids, and their derivatives. The distribution of these secondary metabolites revealed apparent differences among different species. In addition, targeted metabolomic analysis suggested that the secondary metabolite profiles of seven species of Balanophorae showed noticeable differences, and differences were also observed among different growing regions. Finally, five important metabolic markers were screened to successfully distinguish B. laxiflora, B. harlandii, and B. polyandra, including three phenolic acids and two flavonoids. This is the first study to systematically compare both the morphology and secondary metabolites among different sources of Balanophorae, which could provide effective information for identifying diverse species.
Asunto(s)
Metabolómica , Metabolómica/métodos , Cromatografía Líquida de Alta Presión , Flavonoides/metabolismo , Medicamentos Herbarios Chinos , Farmacognosia , Metaboloma , Metabolismo Secundario , Espectrometría de Masas , Hidroxibenzoatos/metabolismo , Extractos VegetalesRESUMEN
AIM: Our study aimed to investigate the correlation between glycated hemoglobin (HbA1c) and adverse prognostic events in patients with diabetes and triple-vessel coronary disease (TVD). METHODS: This study ultimately included 2051 patients with TVD and diabetes. Patients were categorized into five groups based on their HbA1c levels: < 6.0 %, 6.0-6.4 %, 6.5-6.9 %, 7.0-7.9 %, and ≥ 8.0 %. The primary endpoint was all-cause death, and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: The median follow-up time was 5.88 years. During this period, a total of 323 (15.7 %) all-cause deaths and 537 (26.2 %) MACCEs were recorded. The relationship between HbA1c and the risk of endpoint events showed a J-shaped pattern, with the lowest risk observed between 6.0 % and 6.4 %. Further analysis revealed a significant interaction between HbA1c and age. In the subgroup with age < 70 years, as HbA1c increased, the risk of endpoint events gradually rose. While in the subgroup with age ≥70 years, there was an L-shaped relationship between HbA1c and endpoint events, with the highest risk observed in patients with HbA1c < 6.0 %. CONCLUSION: Our study revealed variations in the relationship between HbA1c levels and endpoint events among patients with TVD and diabetes of different ages. In younger patients, elevated HbA1c levels were associated with a higher risk of death and MACCE, while in older patients, excessively low HbA1c levels (HbA1c < 6 %) were linked to a higher risk of death and MACCE.
Asunto(s)
Hemoglobina Glucada , Humanos , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/mortalidad , Factores de Edad , Estudios de Cohortes , Diabetes Mellitus/sangre , Diabetes Mellitus/mortalidad , Factores de Riesgo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Estudios de SeguimientoAsunto(s)
Neoplasias del Sistema Nervioso Central , Humanos , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Masculino , Niño , Femenino , Proteínas de Fusión Oncogénica/genética , Proteínas RepresorasRESUMEN
Atmospheric polycyclic aromatic hydrocarbons (PAHs) and their derivatives are a global problem that influences the environment and threatens human health. To investigate the characteristics, sources, and health risk assessment of PM2.5-bound PAHs and their derivatives, PM2.5 were collected at an urban site in Zibo from November 5 to December 26, 2020, and the concentrations of 16 conventional PAHs, nine NPAHs, and five OPAHs in PM2.5 were analyzed using gas chromatography-mass spectrometry. Source apportionment of PAHs and their derivatives was conducted using diagnostic ratios and a PMF model, and the health risks of PAHs and their derivatives to adult men and women were evaluated using the source-dependent incremental lifetime cancer risk (ILCR) model. The results showed that the average concentrations of ∑16pPAHs, ∑9NPAHs, and ∑5OPAHs in PM2.5 of Zibo City during the sampling period were (41.61 ± 13.40), (6.38 ± 5.70), and (53.20 ± 53.47) ng·m-3, respectively. The concentrations of the three PAHs increased significantly after heating, which were 1.31, 2.04, and 5.24 times larger than those before heating. During the sampling period, Chr, BaP, and BaA were the dominant components of pPAHs; 9N-Ant and 2N-Flt + 3N-Flt were the dominant components of NPAHs; and ATQ and BZO were the dominant components of OPAHs. Source apportionment results showed that motor vehicles were the main source of PAHs and their derivatives in PM2.5 before heating, whereas after heating, the main sources were the mixed source of coal and biomass combustion and secondary formation. The total BaP equivalent (TEQ) was 14.5 ng·m-3 during the sampling period, and the TEQ increased significantly after heating, which was approximately 1.2 times of that before heating. Assisted by the individual PAH source apportionment results, the ILCR of PM2.5-boundPAHs and NPAHs in Zibo City had a certain potential carcinogenic risk for adult males (1.06 × 10-5) and females (9.32 × 10-6). Among them, the health risks of PAHs from gasoline vehicles, diesel vehicles, and coal/biomass combustion were significantly higher than those from other emission sources.
Asunto(s)
Contaminantes Atmosféricos , Neoplasias , Hidrocarburos Policíclicos Aromáticos , Adulto , Femenino , Humanos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Calefacción , Monitoreo del Ambiente/métodos , Medición de Riesgo , Carbón Mineral/análisis , ChinaRESUMEN
Background: The clinically meaningful cardiac troponin I (cTnI) threshold associated with the long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective: To assess the association between different thresholds for post-procedural cTnI and 5-year mortality. Methods: The study included 4059 consecutive patients with normal baseline cTnI values who underwent elective PCI. The post-procedural cTnI level was measured at 8-48 h after PCI. The main study endpoints were 5-year all-cause mortality and cardiovascular mortality. Results: A cTnI ≥5 times the upper reference limit (URL) as defined by the fourth universal definition of myocardial infarction (4th UDMI), ≥35 times as defined by the Academic Research Consortium-2 criteria, and ≥70 times as defined by the Society for Cardiovascular Angiography and Interventions (SCAI [2014]) was identified in 33%, 6.6%, and 3.3% of patients, respectively. During 5 years of follow-up, the all-cause mortality rate was 3.4% (n = 132) and the cardiovascular mortality rate was 2.0% (n = 77). Both all-cause mortality and cardiovascular mortality increased with higher peak cTnI, and were independently predicted by a cTnI ≥70 times the URL (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.20-5.02 and adjusted HR 3.17, 95% CI 1.31-7.67, respectively; reference, cTnI <1 × URL]. The SCAI (2014) threshold was significantly associated with 5-year cardiovascular mortality (adjusted HR 2.66, 95% CI 1.20-5.89; reference, cTnI, <70 × URL) and all-cause mortality (adjusted HR 2.23, 95% CI 1.16-4.30; reference, cTnI <70 × URL). Conclusion: In patients with normal pre-procedural cTnI who underwent elective PCI, a post-procedural cTnI ≥70 times the URL independently predicted 5-year all-cause and cardiovascular mortality. Therefore, only the SCAI (2014) post-procedural cTnI threshold was independently associated with long-term mortality.
RESUMEN
AIMS: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). METHODS: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. RESULTS: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. CONCLUSIONS: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.
Asunto(s)
Síndrome Coronario Agudo , Biomarcadores , Glucemia , Enfermedad de la Arteria Coronaria , Hiperglucemia , Humanos , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medición de Riesgo , Factores de Tiempo , Hiperglucemia/diagnóstico , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Glucemia/metabolismo , Factores de Riesgo , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , China/epidemiologíaRESUMEN
The application of high-performance rubber nanocomposites has attracted wide attention, but its development is limited by the imbalance of interface and network effects caused by fillers. Herein, an ultrastrong polymer nanocomposite is successfully designed by introducing a superhydrophobic and mesoporous silica aerogel (HSA) as the filler to poly(methyl vinyl phenyl) siloxane (PVMQ), which increased the PVMQ elongation at break (â¼690.1%) by â¼9.3 times and the strength at break (â¼6.6 MPa) by â¼24.3 times. Furthermore, HSA/PVMQ with a high dynamic storage modulus (G'0) of â¼12.2 MPa and high Payne effect (ΔG') of â¼9.4 MPa is simultaneously achieved, which is equivalent to 2-3 times that of commercial fumed silica reinforced PVMQ. The superior performance is attributed to the filler-rubber interfacial interaction and the robust filler-rubber entanglement network which is observed by scanning electron microscopy. When the HSA-PVMQ entanglement network is subjected to external stress, both the HSA and bound-PVMQ chains are synergistically involved in resisting structural evolution, resulting in the maximized energy dissipation and deformation resistance through the desorption of the polymer chain and the slip/interpenetrating of the exchange hydrogen bond pairs. Hence, highly aggregated nanoporous silica aerogels may soon be widely used in the application of reinforced silicone rubber or other polymers shortly.
RESUMEN
Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.
What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.
Asunto(s)
Intervención Coronaria Percutánea , Trombocitopenia , Anciano , Femenino , Masculino , Persona de Mediana Edad , Plaquetas , Proteína C-Reactiva/metabolismo , China/epidemiología , Estudios de Cohortes , Inflamación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/estadística & datos numéricos , Estudios Prospectivos , Trombocitopenia/epidemiología , Trombocitopenia/metabolismo , HumanosRESUMEN
Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.
RESUMEN
A simple twin-core D-shape photonic crystal fiber sensor based on surface plasmon resonance (SPR) is designed for the measurement of refractive indices (RI). The twin-core D-shape structure enhances the SPR effect, and the M g F 2-Au dual-layer film narrows the linewidth in the loss spectrum, consequently improving both the sensitivity and figure of merit (FOM). The properties of the sensor are analyzed by the finite element method. In the RI range of 1.32-1.42, the maximum wavelength sensitivity, FOM, and resolution are 62,000 nm/RIU, 1281R I U -1, and 1.61×10-6, respectively.
RESUMEN
High energy and low sensitivity have been the focus of developing new energetic materials (EMs). However, there has been a lack of a quick and accurate method for evaluating the stability of diverse EMs. Here, we develop a machine learning prediction model with high accuracy for bond dissociation energy (BDE) of EMs. A reliable and representative BDE dataset of EMs is constructed by collecting 778 experimental energetic compounds and quantum mechanics calculation. To sufficiently characterize the BDE of EMs, a hybrid feature representation is proposed by coupling the local target bond into the global structure characteristics. To alleviate the limitation of the low dataset, pairwise difference regression is utilized as a data augmentation with the advantage of reducing systematic errors and improving diversity. Benefiting from these improvements, the XGBoost model achieves the best prediction accuracy with R2 of 0.98 and MAE of 8.8 kJ mol-1, significantly outperforming competitive models.
RESUMEN
Rural ecology is a comprehensive field of study that takes the rural social-ecological-economic systems as the objective object and emphasizes spatial carrier governance. The development of rural ecology in the New Era embodies and implements comprehensively the core concepts of Xi Jinping Thought on Socialism with Chinese Cha-racteristics for a New Era, including harmonious coexistence between humans and nature, rural revitalization, green development, and the comprehensive construction of a socialist modernized nation. Under the goal of Chinese-style modernization, rural ecology exhibits characteristics distinct from the past, such as the integration of research objects, the intersectionality of basic theories, the computational feature of technical methods, and the orientation of exporting outcomes. To provide disciplinary support for modernization-oriented science to meet the new demands of country's rural development, effectively narrating the story of sustainable rural development in China and providing fundamental guarantees for the safety of rural systems, a number of issues such as paradigm innovation in research, improvement of data quality, and integration of comprehensive technologies, should be fully considered.
Asunto(s)
Ecología , Población Rural , Humanos , China , Ecosistema , Socialismo , Conservación de los Recursos NaturalesRESUMEN
Post-weaning diarrhea is common in piglets, causing huge economic losses worldwide. Associations between LPS challenge, intestinal inflammation, and microbiota have been reported in Duroc × Landrace × Yorkshire (DLY) crossbred pigs. However, the effects of LPS challenge in other breeds remain unclear. In the current study, we performed a comprehensive comparative analysis of the effects of LPS challenge on jejunal mucosal morphology, jejunal microbial composition, and serum indexes in two pig breeds: DLY and Heigai, an indigenous Chinese breed. The results showed that LPS caused considerable damage to the mucosal morphology, enhanced serum levels of inflammatory cytokines and the intestinal permeability index, and lowered the antioxidant capacity index. LPS challenge also changed the microbial composition and structure of the jejunum, significantly increased the abundances of Escherichia-Shigella in DLY pigs, and decreased those of Gemella and Saccharimonadales in Heigai pigs. Furthermore, LPS challenge triggered functional changes in energy metabolism and activities related to the stress response in the jejunal bacterial community, alleviating the inflammatory response in Heigai pigs. This study also revealed that Heigai pigs had a weaker immune response to LPS challenge than DLY pigs, and identified several genera related to the breed-specific phenotypes of Heigai pigs, including Gemella, Saccharimonadales, Clostridia_UCG_014, Terrisporobacter, and Dielma. Our collective findings uncovered differences between Heigai and DLY pigs in intestinal inflammation and microbiota dysbiosis induced by LPS challenge, providing a theoretical basis for unraveling the mechanism of intestinal inflammation in swine and proposing microbial candidates involved in the resistance to diarrhea in piglets.
RESUMEN
A comprehensive understanding of carrier transport in photoisomeric molecular junctions is crucial for the rational design and delicate fabrication of single-molecule functional devices. It has been widely recognized that the conductance of azobenzene (a class of photoisomeric molecules) based molecular junctions is mainly determined by photoinduced conformational changes. In this study, it is demonstrated that the most probable conductance of amine-anchored azobenzene-based molecular junctions increases continuously upon UV irradiation. In contrast, the conductance of pyridyl-anchored molecular junctions with an identical azobenzene core exhibits a contrasting trend, highlighting the pivotal role that anchoring groups play, potentially overriding (even reversing) the effects of photoinduced conformational changes. It is further demonstrated that the molecule with cis-conformation cannot be fully mechanically stretched into the trans-conformation, clarifying that it is a great challenge to realize a reversible molecular switch by purely mechanical operation. Additionally, it is revealed that the coupling strength of pyridyl-anchored molecules is dramatically weakened when the UV irradiation time is prolonged, whereas it is not observed for amine-anchored molecules. The mechanisms for these observations are elucidated with the assistance of density functional theory calculations and UV-Vis spectra combined with flicker noise measurements which confirm the photoinduced conformational changes, providing insight into understanding the charge transport in photoisomeric molecular junctions and offering a routine for logical designing synchro opto-mechanical molecular switches.