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Metal-organic frameworks (MOFs) are high-performance adsorbents for atmospheric water harvesting but have poor water-desorption ability, requiring excess energy input to release the trapped water. Addressing this issue, a Janus-structured adsorbent with functional asymmetry is presented. The material exhibits contrasting functionalities on either face - a hygroscopic face interfaced with a photothermal face. Hygroscopic aluminum fumarate MOF and photothermal CuxS layers are in-situ grown on opposite sides of a Cu/Al bimetallic substrate, resulting in a CuxS-Cu/Al-MOF Janus hygro-photothermal hybrid. The two faces serve as independent "factories" for photothermal conversion and water adsorption-desorption respectively, while the interfacing bimetallic layer serves as a "heat conveyor belt" between them. Due to the high porosity and hydrophilicity of the MOF, the hybrid exhibits a water-adsorption capacity of 0.161 g g-1 and a fast adsorption rate (saturation within 52 min) at 30% relative humidity. Thanks to the photothermal CuxS, the hybrid can reach 71.5 °C under 1 Sun in 20 min and desorb 97% adsorbed water in 40 min, exhibiting a high photothermal conversion efficiency of over 90%. CuxS-Cu/Al-MOF exhibits minimal fluctuations after 200 cycles, and its water-generation capacity is 3.21 times that of powdery MOF in 3 h in a self-designed prototype in one cycle.
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BACKGROUND: Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. METHODS: Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. RESULTS: We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. CONCLUSIONS: Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.
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Adenocarcinoma , Carcinoma de Células Grandes , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Microdisección , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Adenocarcinoma/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Genómica , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Previous studies have shown that an elevated triglyceride-glucose (TyG) index was associated with all-cause mortality in both general adult individuals and critically ill adult patients. However, the relationship between the TyG index and clinical prognosis in pediatric patients admitted to the intensive care unit (ICU) remains unknown. We aimed to investigate the association of the TyG index with in-hospital all-cause mortality in critically ill pediatric patients. METHODS: A total of 5706 patients in the Pediatric Intensive Care database were enrolled in this study. The primary outcome was 30-day in-hospital all-cause mortality, and secondary outcome was 30-day in-ICU all-cause mortality. The restricted cubic spline (RCS) curves and two-piecewise multivariate Cox hazard regression models were performed to explore the relationship between the TyG index and outcomes. RESULTS: The median age of the study population was 20.5 [interquartile range (IQR): 4.8, 63.0] months, and 3269 (57.3%) of the patients were male. The mean TyG index level was 8.6 ± 0.7. A total of 244 (4.3%) patients died within 30 days of hospitalization during a median follow-up of 11 [7, 18] days, and 236 (4.1%) patients died in ICU within 30 days of hospitalization during a median follow-up of 6 [3, 11] days. The RCS curves indicated a U-shape association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality (both P values for non-linear < 0.001). The risk of 30-day in-hospital all-cause mortality was negatively correlated with the TyG index until it bottoms out at 8.6 (adjusted hazard ratio [HR], 0.72, 95% confidence interval [CI] 0.55-0.93). However, when the TyG index was higher than 8.6, the risk of primary outcome increased significantly (adjusted HR, 1.51, 95% CI 1.16-1.96]). For 30-day in-ICU all-cause mortality, we also found a similar relationship (TyG < 8.6: adjusted HR, 0.75, 95% CI 0.57-0.98; TyG ≥ 8.6: adjusted HR, 1.42, 95% CI 1.08-1.85). Those results were consistent in subgroups and various sensitivity analysis. CONCLUSIONS: Our study showed that the association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality was nonlinear U-shaped, with a cutoff point at the TyG index of 8.6 in critically ill pediatric patients. Our findings suggest that the TyG index may be a novel and important factor for the short-term clinical prognosis in pediatric patients.
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Biomarcadores , Glucemia , Causas de Muerte , Enfermedad Crítica , Bases de Datos Factuales , Mortalidad Hospitalaria , Unidades de Cuidado Intensivo Pediátrico , Triglicéridos , Humanos , Masculino , Enfermedad Crítica/mortalidad , Femenino , Estudios Retrospectivos , Glucemia/metabolismo , Triglicéridos/sangre , Factores de Riesgo , Lactante , Preescolar , Factores de Tiempo , Medición de Riesgo , Biomarcadores/sangre , Pronóstico , Factores de Edad , Niño , Valor Predictivo de las Pruebas , Mortalidad del NiñoRESUMEN
BACKGROUND: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. METHODS: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. RESULTS: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). INTERPRETATION: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.
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Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Masculino , Neoplasias Hepáticas/epidemiología , Femenino , Persona de Mediana Edad , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , China/epidemiología , Hepatitis B/complicaciones , Cirrosis Hepática , Incidencia , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
INTRODUCTION: Insufficient withdrawal duration of antithrombotics leads to excessive bleeding after major surgery. We hypothesize that intraoperative hemoadsorption (HA) can reduce postoperative allogeneic transfusion requirements and excessive bleeding events (EBE), without an increase in ischemic/thromboembolic events (ITE) in patients who have taken antithrombotics and undergone nonelective cardiac surgery. METHODS: A total of 460 patients admitted to our hospital from 2018 to 2022 were included in this study and divided into two groups: HA and non-HA. Because of the risk of bias due to differences in antithrombotic type, withdrawal duration, or basic coagulation function, propensity score matching was used for analyses. RESULTS: Out of 154 cases in the HA group, 144 pairs were successfully matched. No HA safety events such as hemolysis, hypotension, or device failure occurred. After matching, the two groups were found to be comparable in preoperative antithrombotic type, withdrawal duration, platelets and coagulation function, and demographic and perioperative characteristics. Although the HA group did not have a reduced incidence of EBE, this group exhibited significant decreases in the transfusion rate and volume, the incidence of ITE, acute kidney injury, and central nervous system injury. CONCLUSIONS: For patients who have undergone nonelective cardiac surgery and taken antithrombotics, HA can simply and safely rebalance the postoperative coagulation system and have associations with reduced transfusion and postoperative ITE.
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Procedimientos Quirúrgicos Cardíacos , Fibrinolíticos , Humanos , Fibrinolíticos/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Transfusión Sanguínea , Hemorragia/etiología , Incidencia , Sulfadiazina , Estudios RetrospectivosRESUMEN
SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.
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Lesión Renal Aguda , Cistatina C , Recién Nacido , Humanos , Estudios de Cohortes , Creatinina , Estudios Prospectivos , Mortalidad Hospitalaria , BiomarcadoresRESUMEN
The development of economical, energy-saving, and efficient metal-organic framework (MOF)-based adsorbents for atmospheric water collection is highly imperative for the rapid advancement of renewable freshwater resource exploitation. Herein, a feasible one-step solvothermal formation strategy of bimetallic MOF (BMOF) is proposed and applied to construct a solar-triggered monolithic adsorbent for enhanced atmospheric water collection. Benefiting from the reorganization and adjustment of topology structure by Al atoms and Fe atoms, the resultant BMOF(3) consisting of Al-fumarate and MIL-88A has a higher specific surface area (1202.99 m2 g-1 ) and pore volume (0.51 cm3 g-1 ), thereby outperforming the parental MOFs and other potential MOFs in absorbing water. Expanding upon this finding, the solar-triggered monolithic adsorbent is further developed through a bottom-up assembly of polyaniline/chitosan layers and hybridized BMOF(3) skeletons on a glass fiber support. The resultant monolithic adsorbent exhibits superior sorption-desorption kinetics, leading to directional water transport and rapid solar-assisted vapor diffusion. As a proof-of-concept demonstration, an exquisite water harvester is constructed to emphasize a high water yield of 1.19 g g-1 per day of the designed monolithic adsorbent. Therefore, the design and validation of bimetallic MOF-derived solar-triggered adsorbent in this work are expected to provide a reference for the large-scale applications of MOF-based atmospheric water harvesting.
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RATIONALE & OBJECTIVE: Challenges in achieving valid risk prediction and stratification impede treatment decisions and clinical research design for patients with glomerular diseases. This study evaluated whether chronic histologic changes, when complementing other clinical data, improved the prediction of disease outcomes across a diverse group of glomerular diseases. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 4,982 patients with biopsy-proven glomerular disease who underwent native biopsy at 8 tertiary care hospitals across China in 2004-2020. NEW PREDICTORS & ESTABLISHED PREDICTORS: Chronicity scores depicted as 4 categories of histological chronic change, as well as baseline clinical and demographic variables. OUTCOME: Progression of glomerular disease defined as a composite of kidney failure or a ≥40% decrease in estimated glomerular filtration rate from the measurement at the time of biopsy. ANALYTICAL APPROACH: Multivariable Cox proportional hazard models. The performance of predictive models was evaluated by C statistic, time-dependent area under the receiver operating characteristic curve (AUROC), net reclassification index, integrated discrimination index, and calibration plots. RESULTS: The derivation and validation cohorts included 3,488 and 1,494 patients, respectively. During a median of 31 months of follow-up, a total of 444 (8.9%) patients had disease progression in the 2 cohorts. For prediction of the 2-year risk of disease progression, the AUROC of the model combining chronicity score and the Kidney Failure Risk Equation (KFRE) in the validation cohort was 0.76 (95% CI, 0.65-0.87); in comparison with the KFRE model (AUROC, 0.68 [95% CI, 0.56-0.79]), the combined model was significantly better (P = 0.04). The combined model also had a better fit, with a lower Akaike information criterion and a significant improvement in reclassification as assessed by the integrated discrimination improvements and net reclassification improvements. Similar improvements in predictive performance were observed in subgroup and sensitivity analyses. LIMITATIONS: Selection bias, relatively short follow-up, lack of external validation. CONCLUSIONS: Adding histologic chronicity scores to the KFRE model improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases. PLAIN-LANGUAGE SUMMARY: Risk prediction and stratification remain big challenges for treatment decisions and clinical research design for patients with glomerular diseases. The extent of chronic changes is an important component of kidney biopsy evaluations in glomerular disease. In this large multicenter cohort including 4,982 Chinese adults undergoing native kidney biopsy, we evaluated whether histologic chronicity scores, when added to clinical data, could improve the prediction of disease prognosis for a diverse set of glomerular diseases. We observed that adding histologic chronicity scores to the kidney failure risk equation improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases.
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Enfermedades Renales , Insuficiencia Renal Crónica , Insuficiencia Renal , Adulto , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Progresión de la Enfermedad , Riñón/patología , Enfermedades Renales/patología , Insuficiencia Renal/patología , Tasa de Filtración Glomerular , Biopsia , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/patologíaRESUMEN
BACKGROUND: Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults. METHODS: A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension. RESULTS: The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0-6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07-1.55, Q2; aHR, 1.24, 95% CI 1.03-1.49, Q3; aHR, 1.50, 95% CI 1.22-1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04-1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose-response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension. CONCLUSIONS: High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.
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Hipertensión , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Hipertensión/diagnóstico , Hipertensión/epidemiología , China/epidemiología , Glucosa , Triglicéridos , Glucemia , Factores de Riesgo , BiomarcadoresRESUMEN
Background: The prognostic value of coronary artery calcium (CAC) combined with risk factor burdens in middle-aged and elderly patients with symptoms is unclear. Methods: A cohort study comprising 7432 middle-aged and elderly symptomatic patients (aged above 55 years) was conducted between December 2013 and September 2020. All patients had undergone coronary computed tomography angiography, and the Agatston score were used to measure CAC scores. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite outcome of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or coronary artery bypass graft), stroke, and cardiovascular death. Congestive heart failure, cardiogenic shock, malignant arrhythmia, and all-cause mortality were defined as the secondary outcomes. Results: There are 970 (13%) patients with CAC 0-10, 2331 (31%) patients with CAC 11-100, and 4131 (56%) patients with CAC ≥ 101. The proportion of patients aged 55-65 years, 65-75 years and ≥ 75 years was 40.7%, 38.1% and 21.2%, respectively. The total number of MACCEs over the 3.4 years follow-up period was 478. The percentage of CAC ≥ 101 was higher among the 75-year-old group than the 55-65-year-old group, increasing from 46.5% to 68.2%. With the increase in the CAC score, the proportion of patients aged ≥ 75 years increased from 12.9% to 25.8%, compared to those aged 55-65 years. The number of risk factors gradually increased as the CAC scores increased in the symptomatic patients aged over 55 years and the similar tendencies were observed among the different age subgroups. The proportion of non-obstructive coronary artery disease (CAD) was comparable between the three age groups (53.5% vs 51.9% vs 49.1%), but obstruction CAD increased with age. The incidence of MACCE in the group with CAC ≥ 101 and ≥ 4 risk factors was 1.71 times higher (95% confidence interval (CI) 1.01-2.92; p = 0.044) than the rate in the group with CAC ≥ 101 and 1 risk factor. In the CAC 0-10 group, the incidence of MACCE in patients aged ≥ 75 years was 12.65 times higher (95% CI: 6.74-23.75; p < 0.0001) than that in patients aged 55-65 years. By taking into account the combination of CAC score, age, and risk factor burden, the predictive power of MACCE can be increased (area under the curve (AUC) = 0.614). Conclusions: In symptomatic patients aged 55 or above, a rise in age, CAC scores, and risk factor burden was linked to a considerable risk of future MACCE. In addition, combining CAC scores, age and risk factors can more accurately predict outcomes for middle-aged and elderly patients with symptoms.
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The development and progression of autism spectrum disorder (ASD) is characterized by multiple complex molecular events, highlighting the importance of the prefrontal brain regions in this process. Exosomes are nanovesicles that play a critical role in intercellular communication. Peripheral systems influence brain function under both physiological and pathological conditions. We investigated whether this influence was mediated by the direct sensing of peripheral blood exosomes by brain cells. Administration of serum exosomes from rats with valproic acid-induced ASD resulted in ASD-related phenotypes in mice, whereas exosomes from normal rats did not exhibit such effects. RNA sequencing and bioinformatics analysis suggested that negative regulation of medial prefrontal cortex (mPFC) insulin-like growth factor 1 (IGF-1) by exosome-derived miR-29b-3p may contribute to these ASD-associated effects. Further evidence showed that miR-29b-3p-enriched exosomes crossed the blood-brain barrier to reach the mPFC, subsequently inducing the suppression of IGF-1 expression in neurons. Optogenetic activation of excitatory neurons in the mPFC improved behavioral abnormalities in exosome-treated mice. The addition of exogenous IGF-1 or inhibition of miR-29b-3p expression in the mPFC also rescued the ASD-related phenotypes in mice. Importantly, administration of miR-29b-3p-enriched serum exosomes from human donors with ASD into the mouse medial prefrontal cortex was sufficient to induce hallmark ASD behaviors. Together, our findings indicate that blood-brain cross-talk is crucial for ASD pathophysiology and that the brain may sense peripheral system changes through exosomes, which could serve as the basis for future neurological therapies.
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Trastorno del Espectro Autista , Trastorno Autístico , Exosomas , MicroARNs , Ratas , Ratones , Humanos , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Trastorno Autístico/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Trastorno del Espectro Autista/metabolismo , Exosomas/metabolismo , Neuronas/metabolismo , FenotipoRESUMEN
BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insuficiencia Renal Crónica , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , LDL-Colesterol , Estudios Retrospectivos , Insuficiencia Renal Crónica/epidemiología , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiologíaRESUMEN
OBJECTIVE: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. BACKGROUND: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. METHODS: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400). RESULTS: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard ß = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001). CONCLUSION: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.
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Enfermedad de la Arteria Coronaria , Calcificación Vascular , Femenino , Humanos , Masculino , Dolor en el Pecho , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/complicaciones , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Persona de Mediana Edad , AncianoRESUMEN
The N6-methyladenosine (m6A) is involved in the regulation of cell proliferation and metastasis formation in multiple cancers. However, the biological significance of RNA m6A reader IGF2BP1 and the modification of IGF2BP1 itself have not been fully investigated. Here, we analyzed the functions and mechanism of IGF2BP1 in gastric cancer (GC). Results showed that IGF2BP1 upregulated in GC tissue and acted as a predictor of poor prognosis for GC patients. Functionally, IGF2BP1 promoted the migration and aerobic glycolysis of GC cells in vitro. Moreover, IGF2BP1 knockdown repressed the tumor growth in vivo. We also demonstrated that IGF2BP1 directly interacted with c-MYC mRNA via m6A-dependent manner to by stabilize its stability. Overall, these findings demonstrated that m6A reader IGF2BP1 facilitated the carcinogenic of GC in m6A/c-Myc-dependent manner, which might provide critical therapeutic strategy for GC.
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Neoplasias Gástricas , Adenosina/análogos & derivados , Adenosina/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucólisis/genética , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
We study the effects of centralized health management based on hot spring resorts on the physical examination index and sleep quality of people at high risk of chronic diseases. We recruited 114 volunteers at high risk of chronic diseases. We then divided them into 57 in the intervention group and 57 in the control group. The intervention group collectively received 4 weeks (28 days) of comprehensive health management interventions at Tongjing Hotspring Resort, including regular schedules, balanced diet, appropriate exercise, targeted health education, etc. The main outcomes are physical examination indicators (height, weight, waist circumference, blood pressure, lipids, and glucose) and sleep quality. Both groups underwent a questionnaire and physical examination at baseline, 2 weeks and 4 weeks. Intragroup comparisons grouped by exposure criteria showed decreases in BMI, waist circumference, triglycerides, total cholesterol, and blood glucose in the intervention group at both 2 and 4 weeks (all P < 0.05); however, in the control group, only triglycerides decreased at 4 weeks (P < 0.05). Intergroup comparisons showed BMI and waist circumference were significantly lower in the intervention group than in the control group at 4 weeks (all P < 0.05). Intragroup comparisons of insomnia severity index (ISI) scores showed a significant decrease in the intervention group at both 2 and 4 weeks (all P < 0.001) with no significant change in the control group (P > 0.05). Intergroup comparisons showed that the insomnia severity index (ISI) scores were significantly higher in the intervention group than in the control group at baseline (P = 0.006) but became significantly lower than the control group at 2 and 4 weeks (all P < 0.001). Thus, this pattern significantly improved BMI, waist circumference, triglycerides, and sleep in the intervention group. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry: ChiCTR2100053201, registered 14 Nov 2021. (Retroactive Registration).
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Manantiales de Aguas Termales , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Calidad del Sueño , Triglicéridos , Circunferencia de la Cintura , Enfermedad Crónica , Índice de Masa CorporalRESUMEN
Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2-like kinase 1(CLK1), CLK2, and A-kinase anchor protein 8-like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low-risk group, and TME-related pathway gene expression was also higher in low-risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.
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Neoplasias del Colon , Regulación Neoplásica de la Expresión Génica , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Neoplasias del Colon/genética , Expresión Génica , Humanos , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Pronóstico , Empalme del ARN/genética , Factores de Empalme de ARN/genética , ARN Mensajero/genética , Microambiente TumoralRESUMEN
BACKGROUND: Lucitanib is a novel multi-target inhibitor of FGFR1-3, VEGFR 1-3, and PDGFR α/ß. Here, we evaluated the safety, tolerability, and preliminary efficacy of lucitanib in recurrent and metastatic nasopharyngeal carcinoma (RM-NPC). METHODS: Patients with pretreated RM-NPC were randomly divided into two treatment arms: continuous or intermittent treatment. The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). RESULTS: One hundred percent of patients in the continuous arm and 90% of patients in the intermittent arm had at least one treatment-related AE (TRAE). Grade ≥3 related TRAEs occurred in 5 patients in the continuous arm (5/10, 50%). No TRAEs grade >3 occurred in the intermittent arm. The ORR and DCR of the continuous arm was 20% and 90%, and the intermittent arm was 10% and 60%, respectively. All responses were observed by the first evaluation. The duration of response was more than 1 year, with two patients still on treatment with sustained response at more than 3 years. CONCLUSION: Lucitanib has promising clinical activity and tolerable safety profile in heavily pretreated patients with NPC. Patients who responded to lucitanib treatment generally achieved a long DoR. Lucitanib is now being evaluated in phase II/III studies. CLINICALTRIALS.GOV IDENTIFIER: NCT03260179.
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Neoplasias Nasofaríngeas , Quinolinas , Humanos , Naftalenos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Quinolinas/uso terapéuticoRESUMEN
BACKGROUND: The relationship between the dynamic alterations of nutritional indexes before and after surgery, and the prognosis of non-small-cell lung cancer (NSCLC) after radical surgery are unclear. Methods: This study enrolled 100 NSCLC patients in stages I-III who received radical surgery. The preoperative and postoperative 6-month levels of nine nutrition-related indicators were assessed in patients. Survival was analyzed using Kaplan-Meier curves as well as Cox regression models. RESULTS: Patients had better disease-free survival (DFS) with baseline total protein (TP) >76.66 g/L (75% vs. 50%, P = .027), baseline albumin (ALB) >37.7 g/L (60% vs. 26.7%, P = .002), baseline albumin to globulin ratio (AGR) >1.31 (63.5% vs. 40.5%, P = .006), or baseline globulin (GLOB) <31.42 g/L (39.4% vs. 62.7%, P = .037). Moreover, patients with increased hematocrit (HCT) (69.8% vs. 43.9% P = .013) and mean corpuscular volume (MCV) (73.2% vs. 42.4%, P = .014) at the postoperative 6-month examination had superior DFS. Cox proportional hazards regression analyses demonstrated that age >65 years, adenocarcinoma (pathological type), higher baseline TP, and post-surgery elevated HCT independently predicted favorable DFS. CONCLUSION: Lower baseline TP and decreased postoperative HCT levels are independent predictors of prognosis in NSCLC following radical surgical procedures.
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Carcinoma de Pulmón de Células no Pequeñas , Globulinas , Neoplasias Pulmonares , Anciano , Albúminas , Carcinoma de Pulmón de Células no Pequeñas/patología , Globulinas/análisis , Hematócrito , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients' prognoses. METHODS: We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs. RESULTS: During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype. CONCLUSION: The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.
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Enfermedades Cardiovasculares , Predisposición Genética a la Enfermedad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudios de Casos y Controles , Genotipo , Humanos , Mutación , Subunidad p50 de NF-kappa B/genéticaRESUMEN
BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. METHOD: We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan-Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. RESULTS: Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan-Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060-2.277, P = 0.024). CONCLUSIONS: The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.