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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.

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo.

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.

Correlation between novel inflammatory markers and carotid atherosclerosis: A retrospective case-control study.

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.

Development of hypertension models for lung cancer screening cohorts using clinical and thoracic aorta imaging factors.

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.

Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis.

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.

Microcurrent Cloth-Assisted Transdermal Penetration and Follicular Ducts Escape of Curcumin-Loaded Micelles for Enhanced Wound Healing.

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.