Gadoxetic acid-enhanced magnetic resonance imaging in the assessment of hepatic sinusoidal obstruction syndrome in a mouse model.

BACKGROUND: Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome (SOS) in patients with colorectal cancer liver metastases and increases postoperative morbidity and mortality. AIM: To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for diagnosis of hepatic SOS induced by monocrotaline. METHODS: Twenty-four mice were divided into control (n = 10) and experimental (n = 14) groups. The experimental groups were injected with monocrotaline 2 or 6 days before MRI. MRI parameters were: T1 relaxation time before enhancement; T1 relaxation time 20 minutes after enhancement (T1post); a reduction in T1 relaxation time (△T1%); and first enhancement slope percentage of the liver parenchyma (ESP). Albumin and bilirubin score was determined. Histological results served as a reference. Liver parenchyma samples from the control and experimental groups were analyzed by western blotting, and organic anion transporter polypeptide 1 (OATP1) was measured. RESULTS: T1post, △T1%, and ESP of the liver parenchyma were significantly different between two groups (all P < 0.001) and significantly correlated with the total histological score of hepatic SOS (r = -0.70, 0.68 and 0.79; P < 0.001). △T1% and ESP were positively correlated with OATP1 levels (r = 0.82, 0.85; P < 0.001), whereas T1post had a negative correlation with OATP1 levels (r = -0.83; P < 0.001). CONCLUSION: T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.

Efficacy of color Doppler ultrasound and contrast-enhanced ultrasound in identifying vascular invasion in pancreatic ductal adenocarcinoma.

OBJECTIVES: To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. RESULTS: In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. CONCLUSION: CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. CRITICAL RELEVANCE STATEMENT: Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. KEY POINTS: Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency.

Blood-based inflammatory protein biomarker panel for the prediction of relapse and severity in patients with neuromyelitis optica spectrum disorder: A prospective cohort study.

BACKGROUND: To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD. METHODS: This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort. RESULTS: The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort. CONCLUSIONS: Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research.

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.

Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Invalidating environment and meaning in life: The Chain Mediating Effects of regulatory emotional self-efficacy and basic psychological needs satisfaction.

BACKGROUND: Although people strive for meaning in life, life is full of experiences that challenge meaning. According to Bowen's family systems theory, the family is both a relational and an emotional system in which family members influence and are influenced by each other. Invalidating environment, reflecting a deficient family emotional setting, may be a key influencing factor in diminishing meaning in life. Existing studies have not directly explored the effects of the invalidating environment on meaning in life and its underlying mechanism. OBJECTIVE: Guided by Bowen's family systems theory, this study aims to explore the relationship between invalidating environment and meaning in life, as well as the mediating effects of regulatory emotional self-efficacy and the satisfaction of basic psychological needs. METHODS: A sample of 555 university students (62.5 % female, 37.5 % male; Mage =19.13 years old, SD = 1.72) completed questionnaires regarding demographics, invalidating environment, meaning in life, regulatory emotional self-efficacy, and basic psychological needs satisfaction. RESULTS: Results revealed that: (a) invalidating environment negatively predicts meaning in life; (b) regulatory emotional self-efficacy and basic psychological needs satisfaction serve as both independent and chain mediators between invalidating environment and meaning in life. CONCLUSION: Invalidating environment affects meaning in life through regulatory emotional self-efficacy and basic psychological needs satisfaction. This finding has significant theoretical implications and provides a feasible pathway to improve children's meaning in life at both the parent and child levels.

Effect of Curcumin on Promoting Skin Wound Healing in Diabetes Mice / 医药导报

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

A retrospective single-center study of treatment experience of recurrent extracranial malignant germ cell tumor in 19 children / 中华实用儿科临床杂志

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Prussian blue nanoparticles promote wound healing of diabetic skin / 中国组织工程研究

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

BACKGROUND AND AIMS: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. METHODS: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. RESULTS: Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. CONCLUSION: This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

The first nano-cocrystal formulation of marine drug cytarabine with uracil based on cocrystal nanonization strategy for long-acting injection exhibiting enhanced antitumor activity.

To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro/vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level. Along this route, a cocrystal of ARA with UR, viz., ARA-UR, is successfully synthesized and then transformed into nano-cocrystal. The cocrystal structure is precisely confirmed by various methods, demonstrating that a 1:1 ARA and UR in the crystal forms cytosine-UR hydrogen-bonding interactions, thus constructing supramolecular frameworks by strong π-π stacking interplays; while the nano-cocrystal is block-shaped particles of 562.70 nm with zeta potential -33.40 mV. The properties of cocrystal ARA-UR and its nano-cocrystal in vitro/vivo are comparatively explored by theoretical calculations and experimental analyses, revealing that permeability of both is significantly increased than ARA per se. Notably, the meliorative natures of both the cocrystal and nano-cocrystal in vitro bring excellent antitumor activity, but the latter has greater strengths over the former. More notably, the nano-cocrystal can sustain effective concentration for a relatively longer time, causing lengthened retention time and better absorption in vivo. The contribution offers a fire-new dosage form of ARA for long-lasting delivery, thus filling the vacancy in nanococrystal studies about marine drugs.

Layer-specific strain in patients with cardiac amyloidosis using tissue tracking MR.

Background: Cardiac infiltration is the major predictor of poor prognosis in patients with systemic amyloidosis, thus it becomes of great importance to evaluate cardiac involvement. Purpose: We aimed to evaluate left ventricular myocardial deformation alteration in patients with cardiac amyloidosis (CA) using layer-specific tissue tracking MR. Material and Methods: Thirty-nine patients with CA were enrolled. Thirty-nine normal controls were also recruited. Layer-specific tissue tracking analysis was done based on cine MR images. Results: Compared with the control group, a significant reduction in LV whole layer strain values (GLS, GCS, and GRS) and layer-specific strain values was found in patients with CA (all P < 0.01). In addition, GRS and GLS, as well as subendocardial and subepicardial GLS, GRS, and GCS, were all diminished in patients with CA and reduced LVEF, when compared to those with preserved or mid-range LVEF (all P < 0.05). GCS showed the largest AUC (0.9952, P = 0.0001) with a sensitivity of 93.1% and specificity of 90% to predict reduced LVEF (<40%). Moreover, GCS was the only independent predictor of LV systolic dysfunction (Odds Ratio: 3.30, 95% CI:1.341-8.12, and P = 0.009). Conclusion: Layer-specific tissue tracking MR could be a useful method to assess left ventricular myocardial deformation in patients with CA.

Tumor Radiomic Features on Pretreatment MRI to Predict Response to Lenvatinib plus an Anti-PD-1 Antibody in Advanced Hepatocellular Carcinoma: A Multicenter Study.

Introduction: Lenvatinib plus an anti-PD-1 antibody has shown promising antitumor effects in patients with advanced hepatocellular carcinoma (HCC), but with clinical benefit limited to a subset of patients. We developed and validated a radiomic-based model to predict objective response to this combination therapy in advanced HCC patients. Methods: Patients (N = 170) who received first-line combination therapy with lenvatinib plus an anti-PD-1 antibody were retrospectively enrolled from 9 Chinese centers; 124 and 46 into the training and validation cohorts, respectively. Radiomic features were extracted from pretreatment contrast-enhanced MRI. After feature selection, clinicopathologic, radiomic, and clinicopathologic-radiomic models were built using a neural network. The performance of models, incremental predictive value of radiomic features compared with clinicopathologic features and relationship between radiomic features and survivals were assessed. Results: The clinicopathologic model modestly predicted objective response with an AUC of 0.748 (95% CI: 0.656-0.840) and 0.702 (95% CI: 0.547-0.884) in the training and validation cohorts, respectively. The radiomic model predicted response with an AUC of 0.886 (95% CI: 0.815-0.957) and 0.820 (95% CI: 0.648-0.984), respectively, with good calibration and clinical utility. The incremental predictive value of radiomic features to clinicopathologic features was confirmed with a net reclassification index of 47.9% (p < 0.001) and 41.5% (p = 0.025) in the training and validation cohorts, respectively. Furthermore, radiomic features were associated with overall survival and progression-free survival both in the training and validation cohorts, but modified albumin-bilirubin grade and neutrophil-to-lymphocyte ratio were not. Conclusion: Radiomic features extracted from pretreatment MRI can predict individualized objective response to combination therapy with lenvatinib plus an anti-PD-1 antibody in patients with unresectable or advanced HCC, provide incremental predictive value over clinicopathologic features, and are associated with overall survival and progression-free survival after initiation of this combination regimen.

3.0 T unenhanced Dixon water-fat separation whole-heart coronary magnetic resonance angiography: compressed-sensing sensitivity encoding imaging versus conventional 2D sensitivity encoding imaging.

This study was aimed to investigate 3.0 T unenhanced Dixon water-fat whole-heart CMRA (coronary magnetic resonance angiography) using compressed-sensing sensitivity encoding (CS-SENSE) and conventional sensitivity encoding (SENSE) in vitro and in vivo. The key parameters of CS-SENSE and conventional 1D/2D SENSE were compared in vitro phantom study. In vivo study, fifty patients with suspected coronary artery disease (CAD) completed unenhanced Dixon water-fat whole-heart CMRA at 3.0 T using both CS-SENSE and conventional 2D SENSE methods. We compared mean acquisition time, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and the diagnostic accuracy between two techniques. In vitro study, CS-SENSE achieved better effectiveness between higher SNR/CNR and shorter scan times using the appropriate acceleration factor compared with conventional 2D SENSE. In vivo study, CS-SENSE CMRA had better performance than 2D SENSE in terms of the mean acquisition time, SNR and CNR (7.4 ± 3.2 min vs. 8.3 ± 3.4 min, P = 0.001; SNR: 115.5 ± 35.4 vs. 103.3 ± 32.2; CNR: 101.1 ± 33.2 vs. 90.6 ± 30.1, P < 0.001 for both). The diagnostic accuracy between CS-SENSE and 2D SENSE had no significant difference on a patient-based analysis (sensitivity: 97.3% vs. 91.9%; specificity: 76.9% vs. 61.5%; accuracy: 92.0% vs. 84.0%; P > 0.05 for each). Unenhanced CS-SENSE Dixon water-fat separation whole-heart CMRA at 3.0 T can improve the SNR and CNR, shorten the acquisition time while providing equally satisfactory image quality and diagnostic accuracy compared with 2D SENSE CMRA.

Cocrystallization-Driven Double-Optimized Stratagem toward Directional Self-Assembly for the First Ternary Salt Cocrystal of Cardiotonic Drug Milrinone with Different Phenolic Acids Exhibits Optimal In Vitro/Vivo Biopharmaceutical Peculiarities.

The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize in vitro/vivo peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative in vitro properties further modulate the in vivo pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL's biopharmaceutical characteristics on both in vitro and in vivo aspects. Along this line, the first MIL ternary salt cocrystal, viz., [HMIL+-GA-]-MIL-GLC-H2O (denoted as MTSC hereinafter), has been satisfactorily constructed and precisely structurally identified by diversified techniques. The single-crystal X-ray diffraction experiment validates that a molecular salt [HMIL+-GA-] species cocrystallizes with one neutral MIL, two GLC, and five solvent water molecules, among which the organic constituents compose laminated hydrogen bond networks, and then are self-assembled by water molecules to a 3D supramolecular structure. The unique structural feature and stacking pattern of MTSC make both the permeability and solubility be respectively enhanced by 9.69 times and 5.17- to 6.03-fold compared with the parent drug per se. The experimental outcomes are powerfully supported by associated calculations based on density functional theory. Intriguingly, these optimal in vitro physicochemical natures of MTSC have been potently converted into strengths of in vivo pharmacokinetics, showcasing the elevated drug plasma concentration, elongated half-life, alongside advanced bioavailability. Consequently, this presentation not just contributes a brand-new crystalline form with utility values, but ushers in a new dimension of ternary salt cocrystals for improving in vitro/vivo limitations of poor drug bioavailability.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study.

BACKGROUND: Pericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown. METHODS: From January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol ≥ 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis ≥ 50%; the numbers inside the brackets were interquartile ranges. RESULTS: A total of 170 T2DM patients with stable chest pain were included [(mean age 64 ± 10.6 [range 40-85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (- 85.0 [- 89.0, - 82.0] vs. - 79.0 [- 83.5, - 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r = - 0.31, p < 0.001) and lipoprotein(a) level (r = - 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCATRCA density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCATRCA. CONCLUSIONS: In patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a).