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Pulmonary arterial hypertension (PAH) has a subtle onset, rapid progression, and high mortality rate. Imaging evaluation is an important diagnostic and follow-up method for PAH patients. Right ventricular (RV) strain evaluation can identify early changes in RV function and predict the prognosis. Currently, various methods such as tissue Doppler imaging, velocity vector imaging, speckle tracking imaging, and cardiac magnetic resonance imaging can be used to evaluate RV strain in PAH patients. This article aims to summarize the research progress of RV strain imaging evaluation technology in PAH patients, in order to provide a basis for clinical diagnosis and follow-up of PAH patients.
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Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/fisiopatología , Imagen por Resonancia MagnéticaRESUMEN
Purpose: Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes. Methods: A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications. Results: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application. Conclusion: CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.
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Administración Cutánea , Disponibilidad Biológica , Cannabidiol , Portadores de Fármacos , Nanopartículas , Absorción Cutánea , Parche Transdérmico , Cannabidiol/farmacocinética , Cannabidiol/química , Cannabidiol/administración & dosificación , Animales , Absorción Cutánea/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Masculino , Nanopartículas/química , Ratas , Ratas Sprague-Dawley , Tamaño de la Partícula , Piel/metabolismo , Piel/efectos de los fármacos , MicelasRESUMEN
OBJECTIVE: Carotid atherosclerosis is a chronic inflammatory disease, which is a major cause of ischemic stroke. The purpose of this study was to analyze the relationship between carotid atherosclerosis and novel inflammatory markers, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to neutrophil ratio (PNR), neutrophil to lymphocyte platelet ratio (NLPR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), in order to find the best inflammatory predictor of carotid atherosclerosis. METHOD: We included 10015 patients who underwent routine physical examinations at the physical examination center of our hospital from January 2016 to December 2019, among whom 1910 were diagnosed with carotid atherosclerosis. The relationship between novel inflammatory markers and carotid atherosclerosis was analyzed by logistic regression, and the effectiveness of each factor in predicting carotid atherosclerosis was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULT: The level of PLR, LMR and PNR in the carotid atherosclerosis group were lower than those in the non-carotid atherosclerosis group, while NLR, NLPR, SII, SIRI and AISI in the carotid atherosclerosis group were significantly higher than those in the non-carotid atherosclerosis group. Logistic regression analysis showed that PLR, NLR, LMR, PNR, NLPR, SII, SIRI, AISI were all correlated with carotid atherosclerosis. The AUC value of NLPR was the highest, which was 0.67, the cut-off value was 0.78, the sensitivity was 65.8%, and the specificity was 57.3%. The prevalence rate of carotid atherosclerosis was 12.4% below the cut-off, 26.6% higher than the cut-off, and the prevalence rate increased by 114.5%. CONCLUSION: New inflammatory markers were significantly correlated with carotid atherosclerosis, among which NLPR was the optimum inflammatory marker to predict the risk of carotid atherosclerosis.
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Biomarcadores , Enfermedades de las Arterias Carótidas , Inflamación , Humanos , Enfermedades de las Arterias Carótidas/sangre , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios Retrospectivos , Inflamación/sangre , Estudios de Casos y Controles , Anciano , Neutrófilos , Curva ROC , Plaquetas/patología , Plaquetas/metabolismo , Linfocitos , Monocitos/metabolismoRESUMEN
This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann-Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.
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Hipertensión , Neoplasias Pulmonares , Humanos , Aorta Torácica , Calibración , Detección Precoz del Cáncer , Hipertensión/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , NomogramasRESUMEN
NDC80 complex (NDC80C) is composed of four subunits (SPC24, SPC25, NDC80, and NUF2) and is vital for kinetochore-microtubule (KT-MT) attachment during mitosis. Paradoxically, NDC80C also functions in the activation of the spindle-assembly checkpoint (SAC). This raises an interesting question regarding how mitosis is regulated when NDC80C levels are compromised. Using a degron-mediated depletion system, we found that acute silencing of SPC24 triggered a transient mitotic arrest followed by mitotic slippage. SPC24-deficient cells were unable to sustain SAC activation despite the loss of KT-MT interaction. Intriguingly, our results revealed that other subunits of the NDC80C were co-downregulated with SPC24 at a posttranslational level. Silencing any individual subunit of NDC80C likewise reduced the expression of the entire complex. We found that the SPC24-SPC25 and NDC80-NUF2 subcomplexes could be individually stabilized using ectopically expressed subunits. The synergism of SPC24 downregulation with drugs that promote either mitotic arrest or mitotic slippage further underscored the dual roles of NDC80C in KT-MT interaction and SAC maintenance. The tight coordinated regulation of NDC80C subunits suggests that targeting individual subunits could disrupt mitotic progression and provide new avenues for therapeutic intervention. IMPLICATIONS: These results highlight the tight coordinated regulation of NDC80C subunits and their potential as targets for antimitotic therapies.
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Proteínas de Ciclo Celular , Proteínas del Citoesqueleto , Mitosis , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Células HeLa , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genética , Cinetocoros/metabolismo , Puntos de Control de la Fase M del Ciclo Celular/genética , Huso Acromático/metabolismo , Subunidades de Proteína/metabolismo , Subunidades de Proteína/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
OBJECTIVE: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis(BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma(IDC) of the breast. METHODS: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group(57 cases with 57 lesions) and the IDC group(100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic(ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval(CI), and the area under the curve(AUC) for patient age, lesion size, lesion resistive index(RI), and white blood cell(WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods. RESULTS: There were statistically significant differences(Pâ< â0.05) observed between GLM and IDC patients in terms of age, breast pain, the factors in Conventional US(lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS(contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA(white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15âcm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS(US-CEUS) was the highest(97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively. CONCLUSION: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.
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OBJECTIVES: The primary objective of this meta-analysis was to determine whether high-intensity laser therapy (HILT) was effective in improving pain intensity, cervical range of motion (ROM), functional activity, and quality of life (QOL) in individuals with neck pain. DATA SOURCES: PubMed, PEDro, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to March 26, 2022. STUDY SELECTION: Randomized controlled trials (RCTs) involving HILT for neck pain were selected. DATA EXTRACTION AND DATA SYNTHESIS: Two raters were independent in data extraction. The methodological quality was evaluated using the PEDro scale, and the level of evidence was assessed using the GRADE system. RevMan5.4 was used for meta-analysis. RESULTS: Eight RCTs were included and their PEDro scores were moderate to high. Compared with placebo, HILT was effective in improving pain intensity (SMD 2.12, 95%CI 1.24 to 3.00; moderate quality evidence), cervical flexion (SMD 1.31, 95%CI 0.27 to 2.35; moderate quality evidence), extension (SMD 1.43, 95%CI 0.24 to 2.63; moderate quality evidence), right lateral flexion (SMD 1.36, 95%CI 0.15 to 2.56; low-quality evidence). There was a trend of better outcome in functional activity after HILT (SMD 1.73, 95%CI -0.05 to 3.54; low quality evidence). LIMITATIONS: There was limited information available on QOL. CONCLUSION: HILT may be considered as an adjunctive treatment modality for neck pain. There was moderate quality evidence that HILT may improve pain intensity and cervical ROM in individuals with neck pain, but there was low quality evidence that HILT was not effective in improving functional activity. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021254078 CONTRIBUTION OF THE PAPER.
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BACKGROUND: Studies comparing the survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort. METHODS: A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status. RESULTS: There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the KaplanâMeier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022). CONCLUSIONS: HD and PD were not significantly different regarding the survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.
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Diabetes Mellitus , Fallo Renal Crónico , Humanos , Diálisis Renal , Estudios Retrospectivos , Puntaje de Propensión , Fallo Renal Crónico/complicaciones , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: To determine the reliability of shear-wave elastography (SWE)in assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in neutral head posture (NHP) or forward head posture (FHP). METHODS: Sixteen healthy adults (mean age: 21.69 ± 1.01years, 9 females) were included. SWE mode was chosen to measure the nuchal fascia shear modulus and muscle thickness was measured in B-mode. Measurements were collected by two independent investigators on two different days. The intraclass correlation coefficient (ICC) was used to measure the relative reliability, and the standard error of measurement (SEM) were used to measure the absolute reliability. RESULTS: Intrarater (ICC = 0.63-0.89) and inter-rater (ICC = 00.54-0.82) reliability for the nuchal fascia shear modulus were moderate to excellent. Intrarater (ICC = 00.64-0.96) and inter-rater (ICC = 00.48-0.86) reliability for upper cervical muscles thickness were moderate to excellent. The SEM percentage oscillated from 3.27% to 13.55%. There were significant differences(P < 0.05) between NHP and FHP on nuchal fascia shear modulus, right side splenius capitis muscle thickness and left side semispinalis capitis muscle thickness, but no significant differences(P > 0.05) were observed between the right and left sides. The upper cervical muscles thickness of males was significantly thicker(P < 0.01) than females while no significant differences were observed (P > 0.05) on the nuchal fascia shear modulus. CONCLUSIONS: Ultrasound-based SWE may be a reliable tool for assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in clinical practice. REGISTRATION NUMBER: ChiCTR2200055736.
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Two-dimensional metal-organic frameworks (MOFs) have shown great development po-tential in the field of lithium-sulfur (Li-S) batteries. In this theoretical research work, we propose a novel 3d transition metals (TM)-embedded rectangular tetracyanoquinodimethane (TM-rTCNQ) as a potential high-performance sulfur host. The calculated results show that all TM-rTCNQ structures have excellent structural stability and metallic properties. Through exploring different adsorption patterns, we discovered that TM-rTCNQ (TM = V, Cr, Mn, Fe and Co) monolayers possess moderate adsorption strength for all polysulfide species, which is mainly due to the existence of the TM-N4 active center in these frame systems. Especially for the non-synthesized V-rCTNQ, the theoretical calculation fully predicts that the material has the most suitable adsorption strength for polysul-fides, excellent charging-discharging reaction and Li-ion diffusion performance. Additionally, Mn-rTCNQ, which has been synthesized experimentally, is also suitable for further experimental con-firmation. These findings not only provide novel MOFs for promoting the commercialization of Li-S batteries, but also provide unique insights for fully understanding their catalytic reaction mecha-nism.
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OBJECTIVE: The early detection of coronary artery disease (CAD) in diabetes mellitus is a major clinical difficulty. The purpose of this paper is to find out a convenient and economical index to help to screen for patients with CAD in diabetes mellitus. METHOD: From January 2019 to December 2019, a total of 1028 patients hospitalized in the general department of our hospital have been enrolled in our cross-sectional study, of which 190 were diagnosed with CAD and 314 with diabetes. Differences of various factors between the CAD group and the non-CAD group were analyzed. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the efficacy of each factor in predicting CAD. The correlation between calcium/magnesium (Ca/Mg) ratio and the prevalence of CAD in diabetic and non-diabetic people was compared, and the cutoff of Ca/Mg ratio to predict the risk of CAD in diabetic patients was calculated. RESULTS: Logistic regression analysis showed that serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, calcium, magnesium, Ca/Mg ratio, hypertension, diabetes, and smoking history were all associated with CAD. Among them, the AUC value of Ca/Mg ratio was the highest of 0.70. Furthermore, in diabetes patients, the AUC value of Ca/Mg ratio to predict the risk of CAD was 0.72, the cutoff was 2.55, the sensitivity was 77.1%, and the specificity was 53.7%. The prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff, and the prevalence rate increased by 153.5%. CONCLUSION: The Ca/Mg ratio is a good predictor of the risk of CAD in diabetes, higher than the cutoff, the prevalence rate was significantly increased.PLA IN LANGUAGE SUMMARYCAD brings great pain and burden to patient. However, CAD is asymptomatic in quiet a few cases of type 2 diabetes until myocardial infarction or sudden cardiac death occurs. In this study, we explored the association between CAD and various serum factor. We found that the Ca/Mg ratio is of excellent value in screening CAD, especially in diabetes. Moreover, we found that the cutoff of Ca/Mg ratio was 2.55 in diabetic population and the prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff. The Ca/Mg ratio will provide good prediction of the risk of CAD and make early detection easier in diabetes.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Calcio , Estudios Transversales , Magnesio , Factores de Riesgo , Colesterol , Angiografía CoronariaRESUMEN
Purpose: Larger nanoparticles of bioactive compounds deposit high concentrations in follicular ducts after skin penetration. In this study, we investigated the effects of microcurrent cloth on the skin penetration and translocation of large nanoparticle applied for wound repair applications. Methods: A self-assembly of curcumin-loaded micelles (CMs) was prepared to improve the water solubility and transdermal efficiency of curcumin. Microcurrent cloth (M) was produced by Zn/Ag electrofabric printing to facilitate iontophoretic transdermal delivery. The transdermal performance of CMs combined with M was evaluated by a transdermal system and confocal microscopy. The CMs/iontophoretic combination effects on nitric oxide (NO) production and inflammatory cytokines were evaluated in Raw 264.7 cells. The wound-healing property of the combined treatment was assessed in a surgically created full-thickness circular wound mouse model. Results: Energy-dispersive X-ray spectroscopy confirmed the presence of Zn/Ag on the microcurrent cloth. The average potential of M was measured to be +214.6 mV in PBS. Large particle CMs (CM-L) prepared using surfactant/cosurfactant present a particle size of 142.9 nm with a polydispersity index of 0.319. The solubility of curcumin in CM-L was 2143.67 µg/mL, indicating 250-fold higher than native curcumin (8.68 µg/mL). The combined treatment (CM-L+M) demonstrated a significant ability to inhibit NO production and increase IL-6 and IL-10 secretion. Surprisingly, microcurrent application significantly improved 20.01-fold transdermal performance of curcumin in CM-L with an obvious escape of CM-L from follicular ducts to surrounding observed by confocal microscopy. The CM-L+M group also exhibited a better wound-closure rate (77.94% on day 4) and the regenerated collagen intensity was approximately 2.66-fold higher than the control group, with a closure rate greater than 90% on day 8 in vivo. Conclusion: Microcurrent cloth play as a promising iontophoretic transdermal drug delivery accelerator that enhances skin penetration and assists CMs to escape from follicular ducts for wound repair applications.
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Curcumina , Ratones , Animales , Curcumina/farmacología , Curcumina/química , Micelas , Administración Cutánea , Piel , Cicatrización de HeridasRESUMEN
Background: Infection with Helicobacter pylori (H. pylori) can cause chronic gastritis and other digestive tract diseases, and represents a public health concern. Current anti-H. pylori treatment can result in antibiotic resistance and other adverse reactions. Huangqi Jianzhong decoction (HQJZD) is a prescription form of traditional Chinese medicine for chronic gastritis that increases probiotics and inhibits H. pylori. In this study, its anti-bacterial activity against H. pylori receives a preliminary evaluation, and a pharmacology analysis is performed to predict its underlying mechanisms. Methods: Human GES-1 cells are divided into a blank control group, a model group, a HQJZD low-dose (2.08 mg·mL-1), a high-dose group (4.16 mg·mL-1), and a positive control group (amoxicillin, 5 µg·mL-1). After culture, the CCK-8 method is used to detect cell viability; flow cytometry is used to detect cell apoptosis rate; and RT-qPCR is used to detect the expression of mRNA virulence factors, including HpPrtC, OPiA, IceA1, and BabA2. Network pharmacology analysis and molecular docking were performed to explore the mechanisms of HQJZD in treating H. pylori gastritis, based on its anti-H. pylori infection effect. Results: We noted lower cell survival rates in the model group, but higher apoptosis rates and mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 than in the control group (p < 0.05). Compared to the model group, the cell survival rate of each dosage group of Huangqi Jianzhong decoction and the positive control group increased significantly, while the apoptosis rate and the mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 were decreased significantly. The effect in each HQJZD group was dose-dependent (p < 0.05). Network pharmacological analysis involving 159 signaling pathways was used to screen 6 key active components of HQJZD and 102 potential target proteins for the treatment of H. pylori-related gastritis. The molecular docking results revealed that the 6 active compounds had a strong binding ability with the target proteins of ALB, IL-6, AKT1, IL-1B, and JUN. Conclusion: HQJZD effectively increases the proliferation rate of human GES-1 cells after infection, while reducing the level of apoptosis. The mechanism may be related to multiple components, multiple targets and pathways, which provides a scientific basis for further elucidating the mechanism of action, the pharmacodynamic material basis, and the clinical application of HQJZD against H. pylori infection.
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Osteoporosis has a high incidence and a low detection rate. If it is not detected in time, it will cause osteoporotic fracture and other serious consequences. This study showed that the attenuation values of vertebrae on chest CT could be used for opportunistic screening of osteoporosis. This will be beneficial to improve the detection rate of osteoporosis and reduce the incidence of adverse events caused by osteoporosis. INTRODUCTION: To explore the value of the attenuation values of all thoracic vertebrae and the first lumbar vertebra measured by artificial intelligence on non-enhanced chest CT to do osteoporosis screening. METHODS: On base of images of chest CT, using artificial intelligence (AI) to measure the attenuation values (HU) of all thoracic and the first vertebrae of patients who underwent CT examination for lung cancer screening and dual-energy X-ray absorptiometry (DXA) examination during the same period. The patients were divided into three groups: normal group, osteopenia group, and osteoporosis group according to the results of DXA. Clinical baseline data and attenuation values were compared among the three groups. The correlation between attenuation values and BMD values was analyzed, and the predictive ability and diagnostic efficacy of attenuation values of thoracic and first lumbar vertebrae on osteopenia or osteoporosis risk were further evaluated. RESULTS: CT values of each thoracic vertebrae and the first lumbar vertebrae decreased with age, especially in menopausal women and presented high predictive ability and diagnostic efficacy for osteopenia or osteoporosis. After clinical data correction, with every 10 HU increase of CT values, the risk of osteopenia or osteoporosis decreased by 32 ~ 44% and 61 ~ 80%, respectively. And the combined diagnostic efficacy of all thoracic vertebrae was higher than that of a single vertebra. The AUC of recognizing osteopenia or osteoporosis from normal group was 0.831and 0.972, respectively. CONCLUSIONS: The routine chest CT with AI is of great value in opportunistic screening for osteopenia or osteoporosis, which can quickly screen the population at high risk of osteoporosis without increasing radiation dose, thus reducing the incidence of osteoporotic fracture.
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Enfermedades Óseas Metabólicas , Neoplasias Pulmonares , Osteoporosis , Fracturas Osteoporóticas , Humanos , Femenino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Densidad Ósea , Inteligencia Artificial , Detección Precoz del Cáncer , Estudios Retrospectivos , Osteoporosis/diagnóstico por imagen , Absorciometría de Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Vértebras Lumbares/diagnóstico por imagenRESUMEN
Ginkgolide B is a dietary diterpene with multiple pharmacological activities. However, current research on ginkgolide B is not comprehensive. The current study analyzed the metabolic profile of ginkgolide B in vivo and in vitro using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To detect and identify the different metabolites in ginkgolide B, a novel data processing method was used as an assistant tool. A total of 53 different metabolites of ginkgolide B (38 phase I metabolites and 15 phase II metabolites) were detected relative to blank samples. The biotransformation route of ginkgolide B was identified as oxidation, dehydroxylation, hydrogenation, decarbonylation, demethylation, sulfate conjugation, glucose conjugation, methylation, and acetylation. The current study demonstrated a method for rapidly detecting and identifying metabolites and provided useful information to further characterize the pharmacology and mechanism of ginkgolide B. A method for the analysis of other diterpene metabolic components in vivo and in vitro was also established.
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Metaboloma , Animales , Cromatografía Líquida de Alta Presión/métodos , Ginkgólidos , Lactonas , Espectrometría de Masas/métodos , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to evaluate the relationship between polymorphisms in CYP2C19 and the single-dose pharmacokinetics (PKs) of omeprazole in healthy Chinese volunteers. A 20 mg single dose of omeprazole (Losec) enteric-coated capsules or tablets was orally administered to 656 healthy subjects from eight subcenters. The polymorphic alleles of CYP2C19*2, *3, and *17 were determined by Sanger sequencing and Agena mass array. Plasma concentrations of omeprazole were determined by high-performance liquid-chromatography tandem mass spectrometry. PK parameters of area under the concentration versus time curve (AUC)0-t , AUC from zero to infinity (AUC0-∞ ), maximum plasma concentration (Cmax ), and terminal half-life (t1/2 ) were significantly influenced by CYP2C19 phenotype (all p < 0.001) and diplotype (all p < 0.001), and the same results were obtained in the subgroup analysis of the effects of diet and dosage form. The polymorphisms of CYP2C19*2(rs4244285; all PK parameters p < 0.001) and *3(rs4986893; pCmax = 0.020, and the p values of other PK parameters were less than 0.001) were significantly associated with the PKs of omeprazole. For CYP2C19*17 (rs12248560), only t1/2 showed a significant correlation (p = 0.032), whereas other PK parameters did not. The present study demonstrated that the Pks of omeprazole is greatly influenced by CYP2C19.
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Antiulcerosos , Citocromo P-450 CYP2C19 , Omeprazol , Antiulcerosos/farmacocinética , Área Bajo la Curva , China , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Genotipo , Humanos , Omeprazol/farmacocinéticaRESUMEN
OBJECTIVE: To evaluate arteriosclerosis using Cardio-Ankle Vascular Index (CAVI) and to explore the relation between the body fat percentage (BFP) and CAVI. DESIGN: A retrospective observational study. SETTING AND PARTICIPANTS: A total of 1152 patients admitted to a geriatric unit and general practice at a mega hospital in Wuhan, China, from November 2018 to November 2019 were included in this study. PRIMARY OUTCOME: Association between BFP and CAVI. RESULTS: Multiple linear regression analysis showed that BFP was positively correlated with CAVI after correction for potential confounding variables (ß=0.03; 95% CI: 0.01 to 0.05); this association persisted after BFP was treated by quartile categorical variables and the trend test was statistically significant (p for trend=0.002). Meanwhile, the generalised additive model showed a non-linear association between BFP and CAVI. When BFP<20.6%, BFP is not associated with CAVI for (ß=-0.02; 95% CI: -0.06 to 0.03), but when BFP≥20.6%, there is a linear positive association between BFP and CAVI (ß=0.05; 95% CI: 0.02 to 0.07). Subgroup analysis showed that there was an interaction between BFP and CAVI in the age stratification (p interaction=0.038). CONCLUSION: BFP was non-linearly correlated with CAVI, with a 0.05 increase in CAVI for every 1% increase in BFP when BFP≥20.6% and a 0.03 increase in CAVI in those >65 years of age.
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Tobillo , Arteriosclerosis , Tejido Adiposo , Anciano , Estudios Transversales , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex and severe complication of connective tissue disease (CTD). We aimed to evaluate the application value of myocardial perfusion imaging (MPI) in evaluating CTD-associated PAH (CTD-PAH). METHODS: We retrospectively included 88 patients who were diagnosed with CTD between January 2018 and December 2020 at our hospital. Fifty-eight patients had PAH and were included into the CTD-PAH group. Thirty patients without PAH were included in the control group. All patients received routine physical examination, biochemical tests and cardiac function evaluation, right heart catheterization (RHC), and 99m Tc-MIBI MPI. PAH patients were divided into the mild, moderate, and severe PAH group according to their mean pulmonary artery pressures by RHC. Pearson correlation analysis was used to calculate the correlation between the right ventricle target/background (T/B) and right ventricle stroke volume (RV-SV), total pulmonary resistance (TPR), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), 6-minute walk distance (6-MWD), and N-terminal B-type natriuretic peptide (NT-proBNP). The ROC curves of T/B and pulmonary artery pressure classification were plotted and the sensitivity and specificity of T/B in diagnosing PAH of different severities were analyzed. RESULTS: The analysis of correlation revealed that T/B correlated negatively with 6-MWD and positively with NT-proBNP and exhibited good positive correlation with mPAP, TPR, and PVR by RHC and negative correlation with RV-SV. T/B was of the most diagnostic value for severe PAH, and its correlation with severe PAH was stronger than that with mild PAH and moderate PAH. CONCLUSIONS: Target/background is a noninvasive method that can simultaneously evaluate pulmonary arterial pressure and myocardial perfusion of CTD-CHD patients and is particularly of relatively high value for severe PAH patients.
Asunto(s)
Enfermedades del Tejido Conjuntivo , Hipertensión Pulmonar , Imagen de Perfusión Miocárdica , Hipertensión Arterial Pulmonar , Presión Arterial , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Electrocardiografía/efectos adversos , Hipertensión Pulmonar Primaria Familiar/complicaciones , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Imagen de Perfusión Miocárdica/efectos adversos , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Inhibitors of apoptosis (IAPs) are a family of cell death inhibitors found in viruses and metazoans that physically interact with a variety of pro-apoptotic proteins and inhibit apoptosis induced by diverse stimuli. Melanoma IAP (ML-IAP) is a potent anti-apoptotic protein that is strongly upregulated in melanoma and confers protection against a variety of pro-apoptotic stimuli. In the present study, it was revealed that ML-IAP was expressed at high levels in testicular teratoma. Deletion and mutational analysis demonstrated that ML-IAP silencing significantly decreased P19 cell proliferation while inducing cell cycle arrest and apoptosis. ML-IAP knockdown significantly induced caspase-3/8/9-mediated apoptosis in P19 cells. In addition, metabolism and stemness maintenance in P19 cells were suppressed by ML-IAP knockdown. These results indicated that ML-IAP silencing is a powerful inducer of apoptosis mediated by cell death receptors and may function as a direct activator of downstream effector caspases.