Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Identification of pathology-confirmed vulnerable atherosclerotic lesions by coronary computed tomography angiography using radiomics analysis.

OBJECTIVES: To explore whether radiomics-based machine learning (ML) models could outperform conventional diagnostic methods at identifying vulnerable lesions on coronary computed tomographic angiography (CCTA). METHODS: In this retrospective study, 36 heart transplant recipients with coronary heart disease (CAD) and end-stage heart failure were included. Pathological cross-section samples of 350 plaques were collected and coregistered to patients' preoperative CCTA images. A total of 1184 radiomic features were extracted from CCTA images. Through feature selection and stratified fivefold cross-validation, we derived eight radiomics-based ML models for lesion vulnerability prediction. An independent set of 196 plaques from another 8 CAD patients who underwent heart transplants was collected to validate radiomics-based ML models' diagnostic accuracy against conventional CCTA feature-based diagnosis (presence of at least 2 high-risk plaque features). The performance of the prediction models was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI). RESULTS: The training group used to develop radiomics-based ML models contained 200/350 (57.1%) vulnerable plaques and the external validation group was composed of 67.3% (132/196) vulnerable plaques. The radiomics-based ML model based on eight radiomic features showed excellent cross-validation diagnostic accuracy (AUC: 0.900 ± 0.033). In the validation group, diagnosis based on conventional CCTA features demonstrated moderate performance (AUC: 0.656 [95% CI: 0.593 -0.718]), while the radiomics-based ML model showed higher diagnostic ability (0.782 [95% CI: 0.710 -0.846]). CONCLUSIONS: Radiomics-based ML models showed better diagnostic ability than the conventional CCTA features at assessing coronary plaque vulnerability. KEY POINTS: • CCTA has great potential in the diagnosis of vulnerable coronary artery lesions. • Radiomics model built through CCTA could discriminate coronary vulnerable lesions in good diagnostic ability. • Radiomics model could improve the ability of vulnerability diagnosis against traditional CCTA method, sensitivity especially.

Assessment of Coronary Involvement with MDCT and Long-term Outcomes in Patients with Takayasu's Arteritis.

RATIONALE AND OBJECTIVES: Takayasu's arteritis (TA) mainly affects the aorta and its branches involving the coronary arteries. Coronary CT angiography can be used to detect coronary artery lesions. Outcome of TA patients with coronary involvement has not been well established. Our study aimed to systematically analyze coronary lesions in patients with TA and to access long-term outcome in TA patients with coronary involvement. MATERIALS AND METHODS: A retrospective cohort study of TA patients with coronary CT angiography was conducted between January 2009 and October 2021. Baseline clinical characteristics, laboratory parameters, imaging features and therapeutic features were collected and analyzed. Follow-up was scheduled since the onset of TA. Overall survival and major adverse cardiovascular events (MACE) were analyzed in patients with coronary lesions. RESULTS: 48 (59.3%) TA patients had coronary involvement. Coronary ostial stenosis was detected in 31 (64.6%) patients by MDCT. Prevalence of disease activity (p = 0.007) was higher in patients with ostial stenosis. The median follow-up was 10.0 years. Death was observed in nine patients including seven died from myocardial infarction. TA patients with ostial stenosis had higher rate of MACE (p = 0.013). Baseline activity(HR: 5.250, 95%CI 2.004-8.639), ostial involvement(HR:8.954, 95%CI 3.875-56.038), stenosis≥ 70% (HR: 10.822, 95%CI 2.764-61.230) and activity recurrence (HR:11.913, 95%CI 2.321-85.747) were independently associated with increased major cardiovascular events. CONCLUSION: MDCT should be performed in patients suspected with coronary involvement to make early diagnosis. Myocardial ischemia is the major cause of longterm death in TA patients with coronary lesions. Baseline disease activity, coronary ostial stenosis, stenosis ≥ 70% and activity recurrence were independent risk factors of cardiovascular events in TA patients.

Combination of high-frequency electric with 5-ALA photodynamic therapy in cellular angiofibroma of vulva: A case report.

Cellular angiofibroma is a rare benign tumor and difficult to diagnose. Surgery was used in most cases of prior treatment. However, due to the individual differences, this method may be limited, and there is a risk of recurrence. After signing informed consent for treatment, we treated an 18-year-old female with cellular angiofibroma successfully by using the High-Frequency electric pretreatment combined with 5-Aminolevulinic Acid (5-ALA) photodynamic therapy. The tumor was numerous and irregularly shaped on the right labia majora. The specific treatment process was as follows:5-Aminolevulinic Acid (5-ALA) photodynamic therapy was administered after pretreatment with high-frequency electric ion. We did five treatments in total, 10 days apart. And the therapeutic effect was satisfactory for patients. The wound healed well and no recurrence during 12 months follow-up, and the follow-up is continuing. For similar cases, our experience can be taken into account.

Angiographic Lesion Morphology Provides Incremental Value to Generalize Quantitative Flow Ratio for Predicting Myocardial Ischemia.

Aim: The quantitative flow ratio (QFR) is favorable for functional assessment of coronary artery stenosis without pressure wires and induction of hyperemia. The aim of this study was to explore whether angiographic lesion morphology provides incremental value to generalize QFR for predicting myocardial ischemia in unselected patients. Methods: This study was a substudy to the CT-FFR CHINA trial, referring 345 participants from five centers with suspected coronary artery disease on coronary CT angiography for diagnostic invasive coronary angiography (ICA). Fractional flow reserve (FFR) was measured in all vessels with 30-90% diameter stenosis. QFR was calculated in 186 lesions from 159 participants in a blinded manner. In addition, parameters to characterize lesion features were recorded or measured, including left anterior descending arteries (LADs)-involved lesions, side branch located at stenotic lesion (BL), multiple lesions (ML), minimal lumen diameter (MLD), reference lumen diameter (RLD), percent diameter stenosis (%DS), lesion length (LL), and LL/MLD4. Logistic regression was used to construct two kinds of models by combining single or two lesion parameters with the QFR. The performances of these models were compared with that of QFR on a per-vessel level. Results: A total of 148 participants (mean age: 59.5 years; 101 men) with 175 coronary arteries were included for final analysis. In total, 81 (46%) vessels were considered hemodynamically significant. QFR correctly classified 82.29% of the vessels using FFR with a cutoff of 0.80 as reference standard. The area under the receiver operating characteristic curve (AUC) of QFR was 0.86 with a sensitivity, specificity, positive predictive value, and negative predictive value of 80.25, 84.04, 81.25, and 83.16%, respectively. The combined models (QFR + LAD + MLD, QFR + LAD + %DS, QFR + BL + MLD, and QFR + BL + %DS) outperformed QFR with higher AUCs (0.91 vs. 0.86, P = 0.02; 0.91 vs. 0.86, P = 0.02; 0.91 vs. 0.86, P = 0.02; 0.90 vs. 0.86, P = 0.03, respectively). Compared with QFR, the sensitivity of the combined models (QFR + BL and QFR + MLD) was improved (91.36 vs. 80.25%, 91.36 vs. 80.25%, respectively, both P < 0.05) without compromised specificity or accuracy. Conclusion: Combined with angiographic lesion parameters, QFR can be optimized for predicting myocardial ischemia in unselected patients.

Changes in the renal artery and renal volume and predictors of renal atrophy in patients with complicated type B aortic dissection after thoracic endovascular aortic repair.

Background: For complicated Stanford type B aortic dissection (TBAD), thoracic endovascular aortic repair (TEVAR) is the recommended treatment; however, the type of renal artery that should be repaired remains controversial. The study aimed to investigate the changes in the renal artery and renal volume in complicated TBAD after TEVAR and the predictors of renal atrophy. Methods: The cohort study retrospectively enrolled patients with acute and subacute complicated TBAD who underwent aortic computed tomography angiography (CTA) 1 month before as well as 1 week and half a year after TEVAR from January 2010 to May 2017. According to the source of blood supply shown in preoperative CT, the renal artery was classified in 3 ways: type 1, supplied by the aortic true lumen; type 2, supplied by the aortic false lumen; or type 3, supplied by both the true and false lumen. Results: A total of 91 patients (81 men and 10 women) with an average age of 48.12±10.35 years were enrolled. Renal arteries were classified as type 1 (n=91), type 2 (n=35), and type 3 (n=56). There was no difference in the distribution of the 3 types on the left and right sides (type 1 vs. type 2 vs. type 3: 52:39 vs. 15:20 vs. 24:32; P=0.152). After TEVAR, type 3 was more likely to have spontaneous healing than type 2 (16.1% vs. 2.9%; P=0.049). There was no significant difference in the preoperative volume of kidneys of the 3 types (type 1 vs. type 2 vs. type 3: 198.23±38.68 vs. 197.37±41.77 vs. 195.10±36.11 mL; P=0.893). The postoperative volume of types 2 and 3 was smaller than that of type 1 (type 1 vs. type 2 vs. type 3: 190.09±43.25 vs. 165.15±52.63 vs. 170.70±45.28 mL; P=0.006). The renal volume was reduced in all 3 types of renal artery, especially in type 2 (the change of renal volume for type 1 vs. type 2 vs. type 3: -8.14±29.31 vs. -32.22±41.59 vs. -24.41±38.44 mL; P=0.001). The relative change of renal volume for type 1 vs. type 2 vs. type 3: (-3.64±15.69)% vs. (-16.00±21.29)% vs. (-11.97±18.22)%; P=0.001). During the median follow-up of 668 days, 7 patients (7.7%) belonging to types 2 and 3 developed renal atrophy. False lumen thrombosis in the abdominal aorta and/or the renal artery was the predictor of renal atrophy [hazard ratio (HR) =17.757; P=0.008]. Conclusions: Patients with type 2 or 3 renal artery and false lumen thrombosis in the abdominal aorta and/or renal artery should be monitored closely and actively intervened to prevent renal atrophy.

A Specific Assessment of the Normal Anatomy of the Aortic Root in Relation to Age and Gender.

BACKGROUND: A limitation associated with coronary computed tomography angiography (CCTA) is the lack of a normal reference value for aortic root dimensions and the uncertainty of the influence of age and gender on these dimensions. The purpose of the present study was to identify the normal values and variations of aortic root dimensions in healthy individuals and investigate how gender and age affect aortic root size. METHODS: A total of 1286 healthy yellow population (52.7 ± 11.0 years, 634 male) who underwent CCTA were retrospectively included in the present study. Male and female patients were divided into seven groups according to age (< 30 years old, 30-39, 40-49, 50-59, 60-69, 70-79, ≥ 80 years old). In these age groups, we measured and compared the parameters of the aortic root. RESULTS: After body surface area (BSA) correction, the aortic root parameters of females were found to be greater than those of males in the 40-49 age group (P<0.05). There were no significant differences in aortic root parameters between genders in other age groups, except for the diameter of the ascending aorta, which was greater in females (P<0.05). In males, age was positively correlated with aortic root parameters (P<0.05), except for the annulus short diameter and LVOT short diameter. In females, age was positively correlated with aortic root parameters (P<0.05), except for the left coronary ostia height and the LVOT short diameter. CONCLUSION: Aortic root dimensions are affected by age and gender. After BSA correction, females show larger aortic root dimensions than males, and aortic root diameters increase with age.

A Three-Dimensional Deep Convolutional Neural Network for Automatic Segmentation and Diameter Measurement of Type B Aortic Dissection.

OBJECTIVE: To provide an automatic method for segmentation and diameter measurement of type B aortic dissection (TBAD). MATERIALS AND METHODS: Aortic computed tomography angiographic images from 139 patients with TBAD were consecutively collected. We implemented a deep learning method based on a three-dimensional (3D) deep convolutional neural (CNN) network, which realizes automatic segmentation and measurement of the entire aorta (EA), true lumen (TL), and false lumen (FL). The accuracy, stability, and measurement time were compared between deep learning and manual methods. The intra- and inter-observer reproducibility of the manual method was also evaluated. RESULTS: The mean dice coefficient scores were 0.958, 0.961, and 0.932 for EA, TL, and FL, respectively. There was a linear relationship between the reference standard and measurement by the manual and deep learning method (r = 0.964 and 0.991, respectively). The average measurement error of the deep learning method was less than that of the manual method (EA, 1.64% vs. 4.13%; TL, 2.46% vs. 11.67%; FL, 2.50% vs. 8.02%). Bland-Altman plots revealed that the deviations of the diameters between the deep learning method and the reference standard were -0.042 mm (-3.412 to 3.330 mm), -0.376 mm (-3.328 to 2.577 mm), and 0.026 mm (-3.040 to 3.092 mm) for EA, TL, and FL, respectively. For the manual method, the corresponding deviations were -0.166 mm (-1.419 to 1.086 mm), -0.050 mm (-0.970 to 1.070 mm), and -0.085 mm (-1.010 to 0.084 mm). Intra- and inter-observer differences were found in measurements with the manual method, but not with the deep learning method. The measurement time with the deep learning method was markedly shorter than with the manual method (21.7 ± 1.1 vs. 82.5 ± 16.1 minutes, p < 0.001). CONCLUSION: The performance of efficient segmentation and diameter measurement of TBADs based on the 3D deep CNN was both accurate and stable. This method is promising for evaluating aortic morphology automatically and alleviating the workload of radiologists in the near future.

Prevalence of coronary artery disease in symptomatic patients with zero coronary artery calcium score in different age population.

There is controversy about whether symptomatic population with coronary artery calcium score (CACS) of zero have coronary artery disease (CAD) and the distribution at different ages. We sought to analyze the prevalence of CAD in symptomatic patients with zero CACS, especially in different age groups. We studied patients suspected of CAD and underwent CACS scan and coronary computed tomography angiography (CTA). We included patients with CACS of zero. Clinical data was collected to achieve information on demographic characteristics and risk factors. The presence of plaque and obstructive CAD were analyzed based on coronary CTA. The association between age and the prevalence of plaque and obstructive CAD was evaluated.Overall 5514 patients (51.1% men; mean age 54.40 years) were analyzed, of whom 4120 (74.72%) with normal coronary artery, 1394 (25.28%) with plaque and 514 (9.32%) with obstructive CAD. The prevalence of plaque and obstructive CAD increased significantly with age (p < 0.001). Age was significantly associated with the risk of developing plaque and obstructive CAD in the unadjusted model and multivariate model. Taking age less than 40 as a reference, risk ratios (RRs) of prevalence of plaque increased with age in the multivariate model (RR = 2.353 for 40-50, RR = 6.489 for > 70). RRs of prevalence of obstructive CAD also increased with age in the multivariate model (RR = 2.075 for 40-50, RR = 4.102 for > 70). Quite a few CAD could occur in symptomatic patients with CACS of zero, especially in old patients. Coronary CTA was required to exclude CAD in this cohort.

Share Rose, Get Fun: The Influence of Donation on Happiness.

There is little literature on the impact of donation on individual wellbeing in China. This study examines individual donations in China to answer the question of whether helping others makes us happier and to provide policy implications for in Chinese context. Based on the 2012 Chinese General Social Survey (CGSS) data and using ordered logit and OLS as benchmark models, this study finds that donation can significantly increase individual happiness. After using propensity score matching (PSM) to eliminate the possible impact of self-selection, the above conclusion remains robust. After a sub-sample discussion, it is found that this effect is more pronounced under completely voluntary donation behavior, and is not affected by economic factors, indicating that the happiness effect of donation does not vary significantly depending on the individual's economic status. This study contributes to the literature on donation behavior by examining the impact of donation behavior on donors' subjective happiness in China, and further identifies subjective happiness differences, as between voluntary and involuntary donations, thereby providing theoretical and empirical support for the formulation of policies for the development of donation institutions in China.

Sinoatrial nodal artery injury in thoracoscopic epicardial ablation for atrial fibrillation.

OBJECTIVES: This study aimed to clarify the incidence of sinoatrial nodal artery (SANa) injury in thoracoscopic epicardial surgical ablation for atrial fibrillation (AF) and its impact on postoperative outcomes, which have not been previously elucidated. METHODS: We enrolled 103 consecutively patients with AF who underwent thoracoscopic epicardial ablation at our institution. In these patients, we evaluated the postoperative incidence of SANa injury by using enhanced cardiac computed tomography. For patients with confirmed SANa injury, 3-day continuous electrocardiographic monitoring and exercise stress tests were performed to assess the sinus rhythm maintenance and sinus node function. RESULTS: Thirteen patients (12.6%) had a confirmed SANa injury (left anterior type in 6 patients, left posterior type in 2 patients and double-branch type in 5 patients). After a median follow-up of 24 months, the patients with SANa injury were not found to be associated with lower sinus rhythm maintenance (hazard ratio 1.09, 95% confidential interval 0.36-3.31) as compared with those without SANa injury after adjustment for patient characteristics. Sinus node function was evaluated in 7 patients with SANa injury who remained in sinus rhythm after the procedure, and no sinus node dysfunction was confirmed in the 3-day electrocardiographic monitoring and exercise stress tests at a median follow-up of 12 months. CONCLUSIONS: The prevalence of SANa injury in the patients who underwent thoracoscopic epicardial ablation for AF was relatively low, and the incidence of SANa injury was not associated with postoperative restoration of sinus rhythm and sinoatrial node dysfunction. More studies are required to better understand SANa injury.

Effects of two sludge application on fractionation and phytotoxicity of zinc and copper in soil.

The potential harm of heavy metals is a primary concern in application of sludge to the agricultural land. A pot experiment was conducted to evaluate the effect of two sludges on fractionation of Zn and Cu in soil and their phytotoxicity to pakchoi. The loamy soil was mixed with 0%, 20%, 40%, 60% and 80% (by weight) of digested sewage sludge (SS) and composted sludge (SC). The additions of the both sludges caused a significant raise in all fractions, resulting in that exchangeable (EXCH) and organic matter (OM) became predominance for Zn and organic bound Cu occupied the largest portion. There was more available amount for Zn and Cu in SS treatments than SC treatments. During the pot experiment, the concentration of Zn in EXCH, carbonate (CAR) and OM and Cu in EXCH and OM fractions decreased in all treatments, so their bioavailability reduced. Germination rate and plant biomass decreased when the addition rate was high and the best yield appeared in 20% mixtures at the harvest of pakchoi. The two sludges increased tissue contents of Zn and Cu especially in the SS treatments. Zn in pakchoi was not only in relationship to deltaEXCH and deltaCAR forms but also in deltaOM forms in the sludge-soil mixtures. Tissue content of Cu in pakchoi grown on SC-soils could not be predicted by deltaEXCH. These correlation rates between Zn and Cu accumulation in pakchoi and variation of different fractions increased with time, which might indicate that sludges represented stronger impacts on the plant in long-term land application.