Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy.

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Exclusive Core-Janus Satellite Assembly Based on Au-Ag Janus Self-Aligned Distributions with Abundant Hotspots for Ultrasensitive Detection of CA19-9.

The development of surface-enhanced Raman scattering (SERS) probes with high sensitivity and stability is imminent to improve the accuracy of cancer diagnosis. Here, an exclusive core-Janus satellite (CJS) assembly was constructed by a hierarchical assembly strategy in which the Au-Ag Janus satellite is vertically self-aligned on the core surface. In the process, a silica shell template was ingeniously employed to asymmetrically mask the presatellites for the in situ formation of the Janus structure, and a series of Janus satellites with different morphologies were developed by regulating the encapsulated area of the presatellites. The ordered-oriented arrangement of Au-Ag Janus and unique heterojunction morphology permit CJS assemblies, featuring two types of plasmonic nanogaps, including intrananocrevices for individual Janus and internanogaps between neighboring Janus, thereby multiplying the "hotspots" compared to conventional core-monotonous satellites, which contributes to superior SERS activity. As anticipated, the enhancement factor of CJS assemblies was as high as 3.8 × 108. Moreover, it is intriguing that the directional distribution and head physically immobilized by Janus provided uniform and stable SERS signals. The SERS probe based on the CJS assembly for the detection of carbohydrate antigen 19-9 resulted in an ultrahigh sensitivity with a limit of detection of 3.7 × 10-5 IU·mL-1, which is nearly 10 times lower than other SERS probes, and a wide detection range of 3 × 10-5 to 1 × 104 IU·mL-1. The CJS assembly with excellent SERS performance is promising to advance further development of the early diagnosis of pancreatic cancer.

Identification of Myocardial Scarring Using Contrast-Free Cardiac MRI in Patients With Autoimmune Rheumatic Diseases.

BACKGROUND: Late gadolinium enhancement (LGE) cardiac MRI is the method of choice in revealing the presence of myocardial scarring, but its availability remains limited in clinical practice. PURPOSE: To assess myocardial scarring in patients with autoimmune rheumatic diseases (ARDs) using contrast-free cardiac MRI with a radiomics model. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-two patients (mean age, 41 years ± 15, 62 men) with or without ARDs, grouped into a training set of 153 patients and a testing set of 39 patients. FIELD STRENGTH/SEQUENCE: 3.0 T/ cine imaging with a balanced steady-state free precession sequence, T1 mapping with a modified Look-Locker inversion recovery sequence, and LGE imaging with a phase-sensitive inversion recovery gradient echo sequence. ASSESSMENT: LGE assessment was the reference standard for identifying myocardial scarring. Based on motion features extracted from cine images and tissue characterization features extracted from native T1 maps, a fully automated radiomics model with T1, cine MRI, or combined inputs was developed. STATISTICAL TESTS: Logistic regression model was used to detect myocardial scarring using contrast-free cardiac MRI parameters. Receiver operating characteristic curves were analyzed to assess the accuracy, sensitivity, and specificity in detecting myocardial scarring. Sensitivities of the models were further assessed in patients with various myocardial scarring proportions. Z-statistic and dice coefficient were assessed to compare the performance. P-values <0.05 were considered significant. RESULTS: The multivariable regression model exhibited an accuracy of 85.3%, a sensitivity of 93.5%, and a specificity of 50.0%. The radiomics model with T1 and cine MRI input exhibited an accuracy of 75.7%, a sensitivity of 60.9%, and a specificity of 85.5%. Moreover, the radiomics model showed a sensitivity of 90.9% among patients with >25% myocardial scarring. DATA CONCLUSIONS: The proposed radiomics model allowed for the identification of myocardial scarring similar to LGE, but on contrast-free cardiac MRI in patients with ARDs. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Arginine Expedites Erastin-Induced Ferroptosis through Fumarate.

Ferroptosis is a newly characterized form of programmed cell death. The fundamental biochemical feature of ferroptosis is the lethal accumulation of iron-catalyzed lipid peroxidation. It has gradually been recognized that ferroptosis is implicated in the pathogenesis of a variety of human diseases. Increasing evidence has shed light on ferroptosis regulation by amino acid metabolism. Herein, we report that arginine deprivation potently inhibits erastin-induced ferroptosis, but not RSL3-induced ferroptosis, in several types of mammalian cells. Arginine presence reduces the intracellular glutathione (GSH) level by sustaining the biosynthesis of fumarate, which functions as a reactive α,ß-unsaturated electrophilic metabolite and covalently binds to GSH to generate succinicGSH. siRNA-mediated knockdown of argininosuccinate lyase, the critical urea cycle enzyme directly catalyzing the biosynthesis of fumarate, significantly decreases cellular fumarate and thus relieves erastin-induced ferroptosis in the presence of arginine. Furthermore, fumarate is decreased during erastin exposure, suggesting that a protective mechanism exists to decelerate GSH depletion in response to pro-ferroptotic insult. Collectively, this study reveals the ferroptosis regulation by the arginine metabolism and expands the biochemical functionalities of arginine.

An anisotropic nanobox based core-shell-satellite nanoassembly of multiple SERS enhancement with heterogeneous interface for stroke marker determination.

Herein, A novel gold-silver alloy nanobox (AuAgNB)@SiO2-gold nanosphere (AuNP) nanoassembly based on core-shell-satellite structure is fabricated and applied to the surface-enhanced Raman scattering (SERS) detection of S100 calcium-binding protein B protein (S100B). It contains an anisotropic hollow porous AuAgNB core with rough surface, an ultrathin silica interlayer labeled with reporter molecules, and AuNP satellites. The nanoassemblies were systematically optimized by tuning the reporter molecules concentration, silica layer thickness, AuAgNB size, and the size and number of AuNP satellite size. Remarkably, AuNP satellites are adjacent to AuAgNB@SiO2, developing AuAg-SiO2-Au heterogeneous interface. With the strong plasmon coupling between AuAgNB and AuNP satellites, chemical enhancement from heterogeneous interface, and the tip "hot spots" of AuAgNB, the SERS activity of the nanoassemblies was multiply enhanced. Additionally, the stability of nanostructure and Raman signal was significantly improved by the silica interlayer and AuNP satellites. Eventually, the nanoassemblies were applied for S100B detection. It demonstrated satisfactory sensitivity and reproducibility with a wide detection range of 10 fg/mL-10 ng/mL and a limit of detection (LOD) of 1.7 fg/mL. This work based on the AuAgNB@SiO2-AuNP nanoassemblies with multiple SERS enhancements and favorable stability demonstrates the promising application in stroke diagnosis.

Coronary Artery Stent Evaluation by CTA: Impact of Deep Learning Reconstruction and Subtraction Technique.

BACKGROUND. Coronary CTA with hybrid iterative reconstruction (HIR) is prone to false-positive results for in-stent restenosis due to stent-related blooming artifact. OBJECTIVE. The purpose of this study is to assess the impact of deep learning reconstruction (DLR), subtraction images, and the combination of DLR and subtraction images on the diagnostic performance of coronary CTA for the detection of in-stent restenosis. METHODS. This prospective study included patients with coronary stents who underwent coronary CTA between March 2020 and August 2021. CTA used a technique with two breath-holds (noncontrast and contrast-enhanced acquisitions). Conventional and subtraction images were reconstructed for HIR and DLR. The maximum visible instent lumen diameter was measured. Two readers independently evaluated images for in-stent restenosis (≥ 50% stenosis). A simulated assessment of combined conventional and subtraction images was generated, reflecting assessment of conventional and subtraction images in the presence or absence of severe misregistration artifact, respectively. Invasive angiography served as reference standard. RESULTS. The study enrolled 30 patients (22 men and eight women; mean age, 63.6 ± 7.4 [SD] years) with a total of 59 stents; severe misregistration artifact was present for 32 stents. Maximum visible in-stent lumen diameter was higher for DLR than for HIR (2.3 ± 0.5 vs 2.1 ± 0.5 mm, p < .001), and among stents without severe misregistration artifact, it was higher for subtraction than conventional DLR (3.0 ± 0.5 vs 2.4 ± 0.5, p < .001). Among conventional CTA with HIR, conventional CTA with DLR, combination (conventional and subtraction) approach with HIR, and combination (conventional and subtraction) approach with DLR, the highest patient-level diagnostic performance measures were as follows: for reader 1, sensitivity was identical (62.5%), specificity was highest for combination with DLR (90.1%), PPV was highest for combination with DLR (71.4%), NPV was highest for combination with DLR (87.0%), and accuracy was highest for combination with DLR (83.3%); for reader 2, sensitivity was identical (50.0%), specificity was highest for combination with HIR or DLR (both 95.5%), PPV was highest for combination with HIR or DLR (both 80.0%), NPV was highest for combination with HIR or DLR (84.0%), and accuracy was highest for combination with HIR or DLR (both 83.3%). CONCLUSION. The combined DLR and subtraction technique yielded optimal diagnostic performance for detecting in-stent restenosis by coronary CTA. CLINICAL IMPACT. The described technique could guide patient selection for invasive coronary stent evaluation.

Feasibility of 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT in Light-Chain Cardiac Amyloidosis.

BACKGROUND: Systemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (68Ga-FAPI-04) has recently been introduced for imaging fibroblast activation in cardiac diseases. To date, cardiac fibroblast and cardiac amyloidosis (CA) phenotype activities have not been mapped. OBJECTIVES: The aim of this study was to evaluate the feasibility of 68Ga-FAPI-04 positron emission tomography (PET)/computed tomography (CT) in assessing AL CA. METHODS: Thirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwent 68Ga-FAPI-04 PET/CT (107.4 ± 26.5 MBq). Global standardized uptake values and left ventricular (LV) molecular volume were calculated in correlation to echocardiography (n = 30), cardiac magnetic resonance (n = 18), and clinical biomarkers. Subsequently, the patients were categorized as having patchy (PET-patchy), extensive (PET-extensive), and negative (PET-negative) patterns. RESULTS: Of all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally, 68Ga-FAPI-04 uptake was significantly correlated with clinical biomarkers (Mayo stage and N-terminal pro-brain natriuretic peptide), interventricular septal thickness, left ventricular ejection fraction (LVEF), LV end-systolic volume, extracellular volume, and LV global strain (P < 0.05). CONCLUSIONS: 68Ga-FAPI-04 PET/CT is feasible in detecting myocardial fibroblast activation in patients with AL CA in correlation with myocardial remodeling. It might provide complementary information on cardiac molecular characterization and staging of disease.

State of the Art: Quantitative Cardiac MRI in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is characterized by amyloid infiltration in the myocardial extracellular space, causing heart failure. Patients with CA are currently underdiagnosed. Cardiac involvement is significantly associated with the prognosis and treatment decision-making for CA. Early identification and accurate stratification are the crucial first step in patient management. Comprehensive cardiac MRI-based evaluation of the cardiac structure, function, and myocardial tissue characterization assesses cardiac involvement by tracing disease processes. Emerging quantitative tissue characterization techniques have introduced new measures that can identify early staged CA and monitor disease progression or response after treatment. Quantitative cardiac MRI is becoming an instrumental tool in understanding CA, which leads to changes in individualized patient care. This review aimed to discuss the quantitative cardiac MRI-based assessment of CA using established and emerging techniques. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

Parathyroid Hormone-Related Protein Inhibition Blocks Triple-Negative Breast Cancer Expansion in Bone Through Epithelial to Mesenchymal Transition Reversal.

Parathyroid hormone-related protein (PTHrP) plays a major role in skeletal metastasis but its action mechanism has not been fully defined. We previously demonstrated the crucial importance of PTHrP in promoting mammary tumor initiation, growth, and metastasis in a mouse model with a mammary epithelium-targeted Pthlh gene ablation. We demonstrate here a novel mechanism for bone invasion involving PTHrP induction of epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) regulation. Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated Pthlh gene ablation was used to study EMT markers, phenotype, and invasiveness in two triple-negative breast cancer (TNBC) cell types (established MDA-MB-231 and patient-derived PT-TNBC cells). In vitro, Pthlh ablation in TNBC cells reduced EMT markers, mammosphere-forming ability, and CD44high/CD24low cells ratio. In vivo, cells were injected intratibially into athymic nude mice, and therapeutic treatment with our anti-PTHrP blocking antibody was started 2 weeks after skeletal tumors were established. In vivo, compared to control, lytic bone lesion from Pthlh -ablated cells decreased significantly over 2 weeks by 27% for MDA-MB-231 and by 75% for PT-TNBC-injected mice (p < 0.001). Micro-CT (µCT) analyses also showed that antibody therapy reduced bone lytic volume loss by 52% and 48% for non-ablated MDA-MB-231 and PT-TNBC, respectively (p < 0.05). Antibody therapy reduced skeletal tumor burden by 45% and 87% for non-ablated MDA-MB-231 and PT-TNBC, respectively (p < 0.002) and caused a significant decrease of CSC/EMT markers ALDH1, vimentin, and Slug, and an increase in E-cadherin in bone lesions. We conclude that PTHrP is a targetable EMT molecular driver and suggest that its pharmacological blockade can provide a potential therapeutic approach against established TNBC-derived skeletal lesions. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Conservative analysis of Synaptopodin-2 intron sense-overlapping lncRNA reveals its novel function in promoting muscle atrophy.

BACKGROUND: Dissection of the regulatory pathways that control skeletal muscle development and atrophy is important for the treatment of muscle wasting. Long noncoding RNA (lncRNA) play important roles in various stages of muscle development. We previously reported that Synaptopodin-2 (SYNPO2) intron sense-overlapping lncRNA (SYISL) regulates myogenesis through an interaction with enhancer of zeste homologue 2 (EZH2). However, it remains unclear whether SYISL homologues exist in humans and pigs, and whether the functions and mechanisms of these homologues are conserved among species. METHODS: Bioinformatics, cell fractionation, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used for the identification and molecular characterization of SYISL homologues in humans and pigs. Effects on myogenesis and muscle atrophy were determined via loss-of-function or gain-of-function experiments using C2C12 myoblasts, myogenic progenitor cells, dexamethasone (DEX), and aging-induced muscle atrophy models. RNA pulldown, RNA immunoprecipitation, dual luciferase reporting, and co-transfection experiments were used to explore the mechanisms of SYISL interactions with proteins and miRNAs. RESULTS: We identified SYISL homologues in humans (designated hSYISL) and pigs (designated pSYISL). Functional experiments demonstrated that hSYISL and pSYISL regulate myogenesis through interactions with EZH2. Interestingly, we showed that SYISL functions to regulate muscle atrophy and sarcopenia through comparative analysis. SYISL is significantly up-regulated after muscle atrophy (P < 0.01); it significantly promotes muscle atrophy in DEX-induced muscle atrophy models (P < 0.01). SYISL knockdown or knockout alleviates muscle atrophy and sarcopenia in DEX-induced and aged mice. The tibialis anterior (TA) muscle weight of 3-month-old wild-type (WT) mice decreased by 33.24% after DEX treatment (P < 0.001), while the muscle weight loss of 3-month-old SYISL knockout mice was only 18.20% after DEX treatment (P < 0.001). SYISL knockout in 18-month-old WT mice significantly increased the weights of quadriceps (Qu), gastrocnemius (Gas), and TA muscles by 10.45% (P < 0.05), 13.95% (P < 0.01), and 24.82% (P < 0.05), respectively. Mechanistically, SYISL increases the expression levels of the muscle atrophy genes forkhead box protein O3a (FoxO3a), muscle ring finger 1 (MuRF1), and muscle atrophy-related F-box (Atrogin-1) via sponging of miR-23a-3p/miR-103-3p/miR-205-5p and thus promotes muscle atrophy. Additionally, we verified that human SYISL overexpression in muscles of 18-month-old WT mice significantly decreased the weights of Gas, Qu, and TA muscles by 7.76% (P < 0.01), 12.26% (P < 0.05), and 13.44% (P < 0.01), respectively, and accelerates muscle atrophy through conserved mechanisms. CONCLUSIONS: Our results identify SYISL as a conserved lncRNA that modulates myogenesis in mice, pigs, and humans. We also demonstrated its previously unknown ability to promote muscle atrophy.

The impact of deep learning reconstruction on image quality and coronary CT angiography-derived fractional flow reserve values.

OBJECTIVES: To explore the impact of deep learning reconstruction (DLR) on image quality and machine learning-based coronary CT angiography (CTA)-derived fractional flow reserve (CT-FFRML) values. METHODS: Thirty-three consecutive patients with known or suspected coronary artery disease who underwent coronary CTA and subsequent invasive coronary angiography were enrolled. DLR was compared with filtered back projection (FBP), statistical-based iterative reconstruction (SBIR), model-based iterative reconstruction (MBIR) Cardiac, and MBIR Cardiac sharp for objective image qualities of coronary CTA. Invasive fractional flow reserve (FFR) and quantitative flow ratio (QFR) were used as the reference standards. The diagnostic performances of different reconstruction approach-based CT-FFRML were calculated. RESULTS: A total of 182 lesions in 33 patients were enrolled for analysis. The image quality of DLR was superior to the others. There were no significant differences in the CT-FFRML values among these five approaches (all p > 0.05). Of the 182 lesions, 17 had invasive FFR results, and 70 had QFR results. Using FFR as a reference, MBIR Cardiac, MBIR Cardiac sharp, and DLR achieved equal diagnostic performance, slightly higher than the other reconstruction approaches (MBIR Cardiac, MBIR Cardiac sharp, and DLR: AUC = 0.82, FBP and AIDR: AUC = 0.78, all p > 0.05). Using QFR as a reference, the AUCs of FBP, SBIR, MBIR Cardiac, MBIR Cardiac sharp, and DLR were 0.83, 0.81, 0.86, 0.84, and 0.83, respectively (all p > 0.05). CONCLUSIONS: Our study showed that the DLR algorithm improved image quality, but there were no significant differences in the CT-FFRML values and diagnostic performance among different reconstruction approaches. KEY POINTS: • Deep learning-based image reconstruction (DLR) improves the image quality of coronary CTA. • CT-FFRML values and diagnostic performance of DLR revealed no significant differences compared to other reconstruction approaches.

[Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

[Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

The mechanism of action of Fangji Huangqi Decoction on epithelial-mesenchymal transition in breast cancer using high-throughput next-generation sequencing and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FHD) is widely used in traditional Chinese medicine (TCM). FHD has been hypothesized to inhibit the epithelial-mesenchymal transition (EMT) process, which may positively impact breast cancer prevention and treatment. However, its exact mechanism of action is still unknown. AIM OF THE STUDY: This study aimed to screen potential targets of FHD for the treatment of EMT in breast cancer through network pharmacology, and to verify their therapeutic effects in vitro experiments and high-throughput second-generation sequencing. MATERIALS AND METHODS: The data sets of effective components and targets of FHD were established through the Traditional Chinese Medicine Systems Pharmacology database. The GeneCards and OMIM databases were used to establish breast cancer-related target datasets, which were then matched with the TCM target data. The interaction between key target proteins was analyzed using the STRING database; the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the associated biological processes and enriched signal pathways, respectively. The active ingredient disease target network was analyzed using Cytoscape. Finally, next generation sequencing was used to verify the related pathways of FHD intervention in EMT in breast cancer. High-content screening was used to identify the genes/pathways affected by FHD. MDA-MB-231 and HCC-1937 breast cancer cell lines were used to evaluate the impact of FHD on migration, invasion, and EMT. RESULTS: Eighty possible significant targets were identified for the treatment of breast cancer EMT with FHD; GO and KEGG were used to identify 173 cell biological processes associated with breast cancer (P < 0.05), including the NF-κB and PI3K-Akt signaling pathways. The high-throughput sequencing and network pharmacology results were highly consistent. The migration and invasion ability of MDA-MB-231 cells was reduced and their EMT status could be reversed by DSHR2 knockdown. The results of morphology and scratch assays showed that FHD could improve the EMT status of HCC-1973. CONCLUSIONS: This study provides more evidence to support the clinical application of FHD, which has reliable interventional effects on breast cancer EMT. Its therapeutic effects may involve a multi-target, multi-pathway, and multi-mechanism effect.

Diagnostic Improvements of Deep Learning-Based Image Reconstruction for Assessing Calcification-Related Obstructive Coronary Artery Disease.

Objectives: The objective of this study was to explore the diagnostic value of deep learning-based image reconstruction (DLR) and hybrid iterative reconstruction (HIR) for calcification-related obstructive coronary artery disease (CAD) evaluation by using coronary CT angiography (CCTA) images and subtraction CCTA images. Methods: Forty-two consecutive patients with known or suspected coronary artery disease who underwent coronary CTA on a 320-row CT scanner and subsequent invasive coronary angiography (ICA), which was used as the reference standard, were enrolled. The DLR and HIR images were reconstructed as CTADLR and CTAHIR, and, based on which, the corresponding subtraction CCTA images were established as CTAsDLR and CTAsHIR, respectively. Qualitative images quality comparison was performed by using a Likert 4 stage score, and quantitative images quality parameters, including image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated. Diagnostic performance on the lesion level was assessed and compared among the four CCTA approaches (CTADLR, CTAHIR, CTAsDLR, and CTAsHIR). Results: There were 166 lesions of 86 vessels in 42 patients (32 men and 10 women; 62.9 ± 9.3 years) finally enrolled for analysis. The qualitative and quantitative image qualities of CTAsDLR and CTADLR were superior to those of CTAsHIR and CTAHIR, respectively. The diagnostic accuracies of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR to identify calcification-related obstructive diameter stenosis were 83.73%, 69.28%, 75.30%, and 65.66%, respectively. The false-positive rates of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR for luminal diameter stenosis ≥50% were 15%, 31%, 24%, and 34%, respectively. The sensitivity and the specificity to identify ≥50% luminal diameter stenosis was 90.91% and 83.23% for CTAsDLR. Conclusion: Our study showed that deep learning-based image reconstruction could improve the image quality of CCTA images and diagnostic performance for calcification-related obstructive CAD, especially when combined with subtraction technique.

[Technical specification for Instructions for Clinical Application of Chinese Patent Medicines in China Association of Chinese Medicine].

In order to solve the problems of confusion in clinical medication and imperfect instructions in Chinese patent medicines(CPMs), the Standardization Department of the China Association of Chinese Medicine and Center for Pharmacovigilance and Rational use of Chinese Medicine in Beijing University of Chinese Medicine jointly compiled the Instructions for Clinical Application of Chinese Patent Medicines(CPMs). As the interpretation and supplement of drug instruction information, it aims to guide clinical safety and rational use of CPMs. In addition, the technical specification for clinical application description of CPMs has been formulated, which covers the seven processes of "carding instructions, clinical investigation, data retrieval, data screening, evidence classification, path transformation and writing format". It will enable readers of Instructions for Clinical Application of Chinese Patent Medicines to understand the work behind the compilation.

[Pre-searching during formulation of expert consensus on clinical application of Chinese patent medicines:Yanshen Jianwei Capsules as example].

The formulation of expert consensus on clinical application of Chinese patent medicines, in means of exploring the effective combination of experience and evidence to form a research method in line with the characteristics of Chinese patent medicines, is an important transitional stage for clinical researches on Chinese patent medicines. Pre-searching is a new step in the formulation of expert consensus on clinical application of Chinese patent medicines. Before steps of interview and investigation on clinical application, pre-searching is conducted to collect publications and literature on certain variety and similar Chinese patent medicines; the publications on related medical classics and formulas of this variety; the recommendation condition of this variety in clinical practice guidelines and expert consensus; and the medication regimens recommended in disease-specific guidelines. Pre-searching is designed to know about the advantages of certain variety of Chinese patent medicine as well as its potential problems recorded in the literature, which is helpful to find out the clinical positioning of Chinese patent medicines, develop reasonable clinical questions and provide ideas for formal literature searching. However, it is not the direct basis for developing clinical questions. Moreover, interviews and investigations are still needed to further clarify the clinical positioning of Chinese patent medicines and develop reasonable questions. This paper took expert consensus on clinical application of Yanshen Jianwei Capsules as an example to introduce the pre-searching process and methods used during formulation of expert consensus on clinical application of Chinese patent medicines, and to further discuss the role of pre-searching to facilitate the formulation of clinical questions on selection of participants, interventions, controls and outcomes.

Advanced Warning of Aortic Dissection on Non-Contrast CT: The Combination of Deep Learning and Morphological Characteristics.

Background: The identification of aortic dissection (AD) at baseline plays a crucial role in clinical practice. Non-contrast CT scans are widely available, convenient, and easy to perform. However, the detection of AD on non-contrast CT scans by radiologists currently lacks sensitivity and is suboptimal. Methods: A total of 452 patients who underwent aortic CT angiography (CTA) were enrolled retrospectively from two medical centers in China to form the internal cohort (341 patients, 139 patients with AD, 202 patients with non-AD) and the external testing cohort (111 patients, 46 patients with AD, 65 patients with non-AD). The internal cohort was divided into the training cohort (n = 238), validation cohort (n = 35), and internal testing cohort (n = 68). Morphological characteristics were extracted from the aortic segmentation. A deep-integrated model based on the Gaussian Naive Bayes algorithm was built to differentiate AD from non-AD, using the combination of the three-dimensional (3D) deep-learning model score and morphological characteristics. The areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to evaluate the model performance. The proposed model was also compared with the subjective assessment of radiologists. Results: After the combination of all the morphological characteristics, our proposed deep-integrated model significantly outperformed the 3D deep-learning model (AUC: 0.948 vs. 0.803 in the internal testing cohort and 0.969 vs. 0.814 in the external testing cohort, both p < 0.05). The accuracy, sensitivity, and specificity of our model reached 0.897, 0.862, and 0.923 in the internal testing cohort and 0.730, 0.978, and 0.554 in the external testing cohort, respectively. The accuracy for AD detection showed no significant difference between our model and the radiologists (p > 0.05). Conclusion: The proposed model presented good performance for AD detection on non-contrast CT scans; thus, early diagnosis and prompt treatment would be available.

Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/ß-catenin signaling pathway in ovariectomized rats.

Fructus Ligustri Lucidi (FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/ß-catenin signaling in the management of osteoporosis remains largely unknown. To this end, ovariectomized (OVX) rats and primary osteoblasts were administrated with FLL aqueous extract and medicated serum, respectively. Supplement of FLL to OVX rats maintains bone quality by attenuating the reduction in bone mineral density, strength and microstructure. The maintenance may be associated with upregulating the expression of insulin-like growth factor-1, osteoprotegerin, phospho (p)-low-density lipoprotein receptor-related protein 6, p-glycogen synthase kinase 3 beta (GSK3ß), ß-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3ß and p-ß-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. Salidroside may be one of the active ingredients in FLL that are beneficial for bone homeostasis. In summary, our results suggest that FLL may preserve bone quality through induction of canonical Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. And FLL may offer a new source of the DKK1 or SOST inhibitors in protection against osteoporosis.