Electrochemical aerobic Wacker-type oxygenation of triaryl substituted alkenes to 1,2,2-triarylethanones.

An effective synthetic approach for various 1,2,2-triarylethanones from triaryl substituted alkenes has been developed via an electrochemical Wacker-type oxygenation with O2 as the sole oxygen source. It presents the first instance of the Wacker-type oxidation expanding its substrate scope to trisubstituted alkenes. The approach is transition-metal-free, compatible with various functional groups, and can be carried out under mild conditions resulting in satisfactory yields. Mechanistic experiments suggest the CO bond formation occurs through reactions between cationic carbon species and the superoxide radical, which involves the 1,2-shift of the electron-rich substituent.

Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson's Disease: Implications for Gut Microbiota and PGC-1α.

Intestinal dysbiosis plays a critical role in the pathogenesis of Parkinson's disease (PD), and probiotics have emerged as potential modulators of central nervous system function through the microbiota-gut-brain axis. This study aimed to elucidate the anti-inflammatory effects and underlying mechanisms of the probiotic strain Bifidobacterium animalis subsp. lactis NJ241 (NJ241) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The impact of NJ241 was comprehensively assessed in PD mice through behavioral tests, immunofluorescence, Western blotting, enzyme-linked immunosorbent assay (ELISA), 16S rRNA sequencing, and short-chain fatty acid (SCFA) detection. NJ241 exhibited notable efficacy in mitigating MPTP-induced weight loss, gastrointestinal dysfunction, and behavioral deficits in mice. Furthermore, it demonstrated protected against MPTP-induced dopaminergic neuron death and inhibited the activation of glial cells in the substantia nigra (SN). NJ241 demonstrated the ability to normalized dysbiosis in the intestinal microbiota and elevate SCFA levels in PD mice. Additionally, NJ241 reversed MPTP-induced reductions in colonic GLP-1 levels and the expression of GLP-1R and PGC-1α in the SN. Notably, GLP-1R antagonists partially reversed the inhibitory effects of NJ241 on the activation of glial cells in the SN. In summary, NJ241 exerts a neuroprotective effect against MPTP-induced neuroinflammation by enhancing intestinal GLP-1 levels and activating nigral PGC-1α signaling. These findings provide a rationale for the exploration and development of probiotic-based therapeutic strategies for PD.

Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?

Biomaterials, when implanted in the human body, can induce a series of cell- and cytokine-related reactions termed foreign body reactions (FBRs). In the progression of FBRs, macrophages regulate inflammation and healing by polarizing to either a pro-inflammatory or pro-healing phenotype and recruit fibroblasts by secreting cytokines. Stimulated by the biomaterials, fibrotic capsule is formed eventually. The implant, along with its newly formed capsule, introduces various mechanical cues that influence cellular functions. Mechanosensing proteins, such as integrins or ion channels, transduce extracellular mechanical signals into cytoplasm biochemical signals in response to mechanical stimuli. Consequently, the morphology, migration mode, function, and polarization state of the cells are affected. Modulated by different intracellular signaling pathways and their crosstalk, the expression of fibrotic genes increases with fibroblast activation and fibroblast to myofibroblast transition under stiff or force stimuli. However, summarized in most current studies, the outcomes of macrophage polarization in the effect of different mechanical cues are inconsistent. The underlying mechanisms should be investigated with more advanced technology and considering more interfering aspects. Further research is needed to determine how to modulate the progression of fibrotic capsule formation in FBR artificially.

Design, synthesis and biological evaluation of the tumor hypoxia-activated PROTACs bearing caged CRBN E3 ligase ligands.

Tumor hypoxia-activated proteolysis targeting chimeras (ha-PROTACs) 9 and 10 were designed and synthesized by incorporating the hypoxia-activated leaving group (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4­nitrobenzyl into the structure of the cereblon (CRBN) E3 ligand of an epidermal growth factor receptor 19 deletions (EGFRDel19-based PROTAC 8. The in vitro protein degradation assay demonstrated that 9 and 10 could effectively and selectively degrade EGFRDel19 in tumor hypoxia. Meanwhile, these two compounds showed higher potency in inhibiting cell viability and migration, as well as in promoting cells apoptosis in tumor hypoxia. Moreover, nitroreductase reductive activation assay indicated that prodrugs 9 and 10 could successfully release the active compound 8. This study confirmed the feasibility to develop ha-PROTACs to enhance the selectivity of PROTACs by caging CRBN E3 ligase ligand.

Huangkui capsule alleviates doxorubicin-induced proteinuria via protecting against podocyte damage and inhibiting JAK/STAT signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC), a Chinese patent medicine, has been widely used in China as adjuvant therapy for chronic kidney disease (CKD). It displays superior anti-proteinuria efficacy than losartan in patients with CKD at stages 1-2, however, the mechanism of HKC alleviating proteinuria has not been well elucidated. AIM OF THE STUDY: This study aims to confirm the therapeutic effect and investigate associated underlying mechanism of HKC against proteinuria by in vivo and in vitro experiments. MATERIALS AND METHODS: We established a doxorubicin (DOX) induced proteinuria mouse model to evaluate kidney function by biochemical markers measurement and to observe histopathological alterations by hematoxylin and eosin (H&E), Masson's trichrome and Periodic Acid-Schiff (PAS)-stained sections of renal, respectively. Moreover, the expressions of Nephrin and Podocin were measured by immunohistochemistry (IHC) and western blotting analysis to investigate podocyte damage. Furthermore, we established Mouse Podocyte Clone-5 (MPC-5) injury model to identify the active components of HKC against podocyte damage by detecting the expressions of Nephrin, Podocin, and ZO-1 proteins. At last, the key protein levels of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were assessed by western blotting analysis to explore the underlying mechanism of HKC against proteinuria. RESULTS: Our results showed that HKC administration for three consecutive weeks dose-dependently ameliorated both renal function and histopathological damages, elevated the expressions of Nephrin and Podocin, the pivotal molecules maintaining filtration function of the podocyte, indicating the promising protective effect against podocyte injury under DOX exposure. Consistently, in vitro experiments showed HKC administration effectively reversed the abnormal expressions of Nephrin and Podocin in MPC-5 cells treated with DOX, suggesting its protective effect against podocyte injury to maintain filtration barrier integrity. In addition, Hibifolin was identified as the most active ingredients in HKC, which suppressed upstream JAK2/STAT3 and PI3K/Akt pathway phosphorylation to maintain the structural and functional integrity of podocyte filtration barrier. Of note, AG490, a selective JAK2 inhibitor, was used to further affirm the role of Hibifolin involving in regulation JAK2/STAT3. CONCLUSIONS: Our study suggested that HKC may protect podocytes via JAK2/STAT3 and PI3K/Akt pathway to display its effects of ameliorating proteinuria.

Case report: Lymph node metastases of breast cancer and thyroid cancer encountered in axilla.

Occurrences of breast cancer and thyroid cancer metachronously or synchronously are common for women, but axillary lymph node metastasis from both cancers is rarely seen. We report a patient who had two metastatic lymph nodes from papillary thyroid carcinoma after axillary lymph node dissection with mastectomy. Papillary thyroid carcinoma diagnosis was ensured after thyroidectomy. A literature review revealed that even the co-occurrence of breast cancer and thyroid cancer is not rare, but the etiology behind this phenomenon is not elucidated well. Genetic disorders, thyroid dysfunction, and hormone receptors may be relevant. Considering the rareness of axillary lymph node metastasis of thyroid cancer, adjuvant therapy and surgery treatment for this kind of case should be considered elaborately.

Unveiling Local Electronic Structure of Lanthanide-Doped Cs2 NaInCl6 Double Perovskites for Realizing Efficient Near-Infrared Luminescence.

Lanthanide ion (Ln3+ )-doped halide double perovskites (DPs) have evoked tremendous interest due to their unique optical properties. However, Ln3+ ions in these DPs still suffer from weak emissions due to their parity-forbidden 4f-4f electronic transitions. Herein, the local electronic structure of Ln3+ -doped Cs2 NaInCl6 DPs is unveiled. Benefiting from the localized electrons of [YbCl6 ]3- octahedron in Cs2 NaInCl6 DPs, an efficient strategy of Cl- -Yb3+ charge transfer sensitization is proposed to obtain intense near-infrared (NIR) luminescence of Ln3+ . NIR photoluminescence (PL) quantum yield (QY) up to 39.4% of Yb3+ in Cs2 NaInCl6 is achieved, which is more than three orders of magnitude higher than that (0.1%) in the well-established Cs2 AgInCl6 via conventional self-trapped excitons sensitization. Density functional theory calculation and Bader charge analysis indicate that the [YbCl6 ]3- octahedron is strongly localized in Cs2 NaInCl6 :Yb3+ , which facilitates the Cl- -Yb3+ charge transfer process. The Cl- -Yb3+ charge transfer sensitization mechanism in Cs2 NaInCl6 :Yb3+ is further verified by temperature-dependent steady-state and transient PL spectra. Furthermore, efficient NIR emission of Er3+ with the NIR PLQY of 7.9% via the Cl- -Yb3+ charge transfer sensitization is realized. These findings provide fundamental insights into the optical manipulation of Ln3+ -doped halide DPs, thus laying a foundation for the future design of efficient NIR-emitting DPs.

miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc.

BACKGROUND: Cancer stem cells (CSCs) have been implicated in tumorigenesis and tumor recurrence and metastasis are key therapeutic targets in cancer treatment. MicroRNAs display therapeutic potential by controlling the properties of CSCs; however, whether an association exists between miR-3682-3p and CSCs is unknown. AIM: To investigate the mechanism by which miR-3682-3p promotes stemness maintenance in hepatocellular carcinoma (HCC). METHODS: MiR-3682-3p expression in HCC cell lines and 34 pairs of normal and HCC specimens was assayed by quantitative polymerase chain reaction. The functional role of miR-3682-3p was investigated in vitro and in vivo. Dual-luciferase reporter and chromatin immunoprecipitation assays were performed for target asse ssment, and western blotting was utilized to confirm miR-3682-3p/target relationships. RESULTS: We found that miR-3682-3p plays a key role in HCC pathogenesis by promoting HCC cell stemness. The upregulation of miR-3682-3p enhanced CSC spheroid-forming ability, side population cell fractions, and the expression of CSC factors in HCC cells in vitro and the tumorigenicity of transplanted HCC cells in vivo. Furthermore, silencing miR-3682-3p prolonged the survival of HCC-bearing mice. Mechanistically, we found that miR-3682-3p targets FOXO3 and enables FOXO3/ß-catenin interaction, which promotes c-Myc expression through PI3K/AKT; c-Myc, in turn, activates miR-3682-3p, forming a positive feedback loop. Intriguingly, miR-3682-3p expression was induced by hepatitis B virus X protein (HBx) and was involved in HBx-induced tumor stemness-related pathogenesis. CONCLUSION: Our findings reveal a novel mechanism by which miR-3682-3p promotes stemness in HCC stem cells. Silencing miR-3682-3p may represent a novel therapeutic strategy for HCC.

Impact of Foreign Language Classroom Anxiety on Higher Education Students Academic Success: Mediating Role of Emotional Intelligence and Moderating Influence of Classroom Environment.

The current study aimed to investigate the impact of foreign language classroom anxiety (FLCA) on academic success through mediating role of emotional intelligence communication (EIC) and moderating role of class room environment. Due to the disruptive impacts of the COVID-19 pandemic, teaching and learning were moved online nation-wide. The convenient sampling technique was used, for data collection from Chinese university students. There was a total of 615 students that participated in the survey and data gathered in 5 months from November 2021 till March 2022. Covariance-based structural equation modeling (CB-SEM) in SPSS V.25 and AMOS V.22 was used to assess model fitness and hypotheses, as well as construct reliability and validity of the measurement model. The results revealed that FLCA is negatively and significantly influence students' academic success. Furthermore, EIC as a mediator significantly and positively mediates the relationship between FLCA and academic success. The current study shows that emotional intelligence has the ability to reduce students' foreign language anxiety and so improve their language skills. Lastly, classroom environment positively and significantly moderates the relationship between FLCA and emotional intelligence communication.

Boosting Near-Infrared Luminescence of Lanthanide in Cs2 AgBiCl6 Double Perovskites via Breakdown of the Local Site Symmetry.

Currently, lanthanide (Ln3+ )-doped near-infrared (NIR)-emitting double perovskites (DPs) suffer from low photoluminescence quantum yield (PLQY). Herein, we develop a new class of NIR-emitting DPs based on Ln3+ -doped Cs2 (Na/Ag)BiCl6 . Benefiting from the Na+ -induced breakdown of local site symmetry in the Cs2 AgBiCl6 DPs, effective NIR emissions of Ln3+ are realized through Bi3+ sensitization. Specifically, 7.3-fold and 362.9-fold enhanced NIR emissions of Yb3+ and Er3+ are achieved in Cs2 Ag0.2 Na0.8 BiCl6 DPs relative to those in Na-free Cs2 AgBiCl6 counterparts, respectively. The optimal absolute NIR PLQYs for Yb3+ and Er3+ in Cs2 Ag0.2 Na0.8 BiCl6 DPs are determined to be 19.0 % and 4.3 %, respectively. Raman spectroscopy and first-principles density functional theory calculations verify the sublattice distortion in Cs2 (Na/Ag)BiCl6 DPs via Na+ doping. These findings provide fundamental insights into the design of efficient NIR-emitting Ln3+ -doped DPs for versatile optoelectronic applications.

Design, Synthesis, and Biological Evaluation of 2-Anilino-4-Triazolpyrimidine Derivatives as CDK4/HDACs Inhibitors.

Purpose: To enhance the cytotoxicities of our obtained CDK4 inhibitors and get CDK4/HDACs inhibitors with potent enzymatic inhibitory and anti-proliferative activities. Methods: A series of novel CDK4/HDACs inhibitors were designed and synthesized by incorporating the HDAC pharmacophores (hydroxylamine or o-diaminoaniline) into the basic structure of our newly obtained 2-anilino-4-triazolpyrimidine based CDK4 inhibitors. The enzymatic inhibitory (HDAC1, CDK2, CDK4, and CDK6) activities and cytotoxicities of these compounds were evaluated. Moreover, HDAC isoforms inhibitory activity, cell cycle arrest assay, cell apoptosis analysis, cell migration, and cell colony formation assay were performed for the representative compound 11k. Results: Most of these compounds showed excellent HDAC1 inhibitory activities (IC50s: 0.68~244.5 nM) and anti-proliferative activities against cancer cell lines. Some compounds displayed potent CDK4 inhibitory activities and a certain selectivity towards CDK2 and CDK6. Compound 11k exhibited potent enzymatic (CDK4: IC50=23.59 nM; HDAC1: IC50=61.11 nM; HDAC2: IC50=80.62 nM; HDAC6: IC50=45.33 nM) and anti-proliferative activities against H460, MDA-MB-468, HCT116, and HepG2 cell lines with IC50 values 1.20, 1.34, 2.07, and 2.66 µM, respectively. Further mechanistic studies revealed that compound 11k could arrest the cell cycle in G0/G1 phase and induce apoptosis in HCT116 and MDA-MB-468 cells. In addition, compound 11k significantly inhibited the migration and cell colony formation of H460 and HCT116 cells. Conclusion: This study suggested that the incorporation of the HDAC pharmacophore into CDK4 inhibitor scaffold to design CDK/HDAC inhibitors might be a tractable strategy to enhance the antitumor potency of compounds.

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating ß-catenin/c-Jun/MYH9/USP7/c-Myc axis.

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed. In vivo and in vitro experiments were conducted to explore the effects and molecular basis of ENKUR and CB in HCC. ENKUR expression was correlated with HCC progression and patient prognosis. Furthermore, ENKUR could inhibit tumor proliferation, metastasis, and sorafenib resistance in HCC. Mechanistic studies showed that ENKUR or its Enkurin domain could bind to MYH9 and decrease its expression by binding to ß-catenin and inhibiting its nuclear transfer, thus decreasing c-Jun level. Low expression of MYH9 suppressed recruitment of deubiquitination enzyme USP7, promoting degradation of the c-Myc. Therefore, cell cycle and EMT signals were suppressed. CB as a safe and effective anti-cancer compound up-regulates the expression of ENKUR via inhibiting PI3K/AKT/c-Jun-mediated transcription suppression. These findings show that ENKUR induced by CB antagonizes ß-catenin/c-Jun/MYH9/USP7 pathway, thus increasing c-Myc ubiquitin degradation and finally suppressing cell cycle and EMT signals.

Highly efficient NIR-II luminescent I-III-VI semiconductor nanoprobes based on AgInTe2:Zn/ZnS nanocrystals.

Highly efficient luminescence of AgInTe2:Zn/ZnS nanocrystals with the maximum NIR-II quantum yield of 25.2% has been designed through elaborately manipulating the structure to reduce their internal and surface defects. These AgInTe2:Zn/ZnS nanoprobes were employed for sensitive homogeneous biodetection of xanthine oxidase with the limit of detection down to 25 nU L-1.

Coiled-Coil Domain-Containing Protein 45 Is a Potential Prognostic Biomarker and Is Associated with Immune Cell Enrichment of Hepatocellular Carcinoma.

Objective: The role of coiled-coil domain-containing protein 45 (CCDC45) in the development of hepatocellular carcinoma (HCC) has not been reported. The present study is aimed at investigating the expression and prognosis of CCDC45 in HCC and its relevance to immune infiltration. Methods: We conducted CCDC45 expression analysis using The Cancer Genome Atlas (TCGA) tumor database, the Human Protein Atlas (HPA) database, and the Tumor Immunological Evaluation Resource (TIMER). We used the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) database to show the correlation of CCDC45 with clinical features. We examined the prognostic impact of CCDC45 expression levels on HCC patients with the Kaplan-Meier mapper database. Genes coexpressed with CCDC45 and its regulators were also identified using LinkedOmics. The enriched Gene Ontology (GO) categories and associated signaling pathways were estimated using GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Assay (GSEA) pathway data. Correlations between CCDC45 and cancer immune infiltration was analyzed through the TIMER and an integrated repository portal for Tumor-Immune System Interactions (TISIDB) databases. Results: The expression of CCDC45 was elevated in HCC tissues compared to adjacent liver tissues, and overexpression of CCDC45 was significantly correlated with tumor stage. Furthermore, HCC patients with CCDC45 overexpression had a shorter overall survival (OS). Functional network analysis indicated that CCDC45 was involved in homologous recombination, spliceosome, and DNA replication. Interestingly, CCDC45 expression was positively correlated with the level of immune cell infiltration. Conclusions: CCDC45 is associated with prognosis and immune infiltration of HCC and may be a potential therapeutic target for HCC.

Development of hypoxia-activated PROTAC exerting a more potent effect in tumor hypoxia than in normoxia.

Hypoxia is a hallmark of many solid tumors, and it causes the overexpression of a variety of proteins including the epidermal growth factor receptor (EGFR). Many antitumor prodrugs have been designed to target hypoxia. Here we report the identification of a kind of hypoxia-activated proteolysis targeting chimera (ha-PROTAC) by introducing the hypoxia-activated leaving group (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4-nitrobenzyl into the structure of an EGFRDel19-based PROTAC. Among the obtained molecules, ha-PROTAC 13 exhibits a more potent degradation activity for EGFRDel19 in hypoxia than in normoxia in HCC4006 cells. This is the first example of identifying a PROTAC to selectively act on tumors utilizing the characteristic of tumor hypoxia and provides a new approach for PROTAC development.

Enhancing multiphoton upconversion emissions through confined energy migration in lanthanide-doped Cs2NaYF6 nanoplatelets.

Lanthanide (Ln3+)-doped upconversion (UC) nanocrystals have drawn tremendous attention because of their intriguing optical properties. Currently, it is highly desired but remains challenging to achieve efficient multiphoton UC emissions. Herein, we report the controlled synthesis of a new class of UC nanocrystals based on Cs2NaYF6:Yb/Tm nanoplatelets (NPs), which can effectively convert the 980 nm light to five-photon and four-photon UC emissions of Tm3+ without the fabrication of a complicated core/multishell structure required in traditional nanocrystals. Particularly, the as-prepared Cs2NaYF6:Yb/Tm NPs exhibit a maximal UV-to-NIR emission intensity ratio of 1.2, which is the highest among Tm3+-doped core-only UC nanocrystals. We reveal that the enhanced multiphoton UC emissions may benefit from the confined energy migration of Ln3+ dopants in the unique two-dimensional-like structure of Cs2NaYF6 NPs. As such, intense red and green UC emissions of Eu3+ and Tb3+ can further be generated via the cascade sensitization of Tm3+ and Gd3+ in Cs2NaYF6:Yb/Tm/Gd/Eu and Cs2NaYF6:Yb/Tm/Gd/Tb NPs, respectively. These results validate the superiority of Cs2NaYF6 for the future design of efficient UC nanocrystals towards versatile applications.

Rapid and accurate detection of phosphate in complex biological fluids based on highly improved antenna sensitization of lanthanide luminescence.

Rapid and accurate detection of phosphate (Pi) in complex biological fluid is of critical importance for timely warning of Pi accumulation and monitoring Pi related pathological process. Up to date, various luminescent probes have been developed for Pi determination in aqueous media. However, the huge obstacles of the current probes suffer from the inherent issues such as time-consuming, tedious preparation and unavoidable background interference during Pi detection. To circumvent this limitation, we proposed a universal and facile strategy to fabricate a novel sensitizer-Ln3+@surfactant micelle probe with time-resolved luminescent (TRL) superiority through the self-assembly of sensitizer, Ln3+ and surfactant. Through this design, the sensitizer-Ln3+ chelate can be encapsulated into the surfactant constructed micelle and Ln3+ luminescence can be substantially lighted up through the effective energy transfer from the coordinated sensitizer and the assistance of Triton X-100. Such high TRL signal can be sensitively and specifically quenched by Pi, which was attributed to the specific coordination competition between sensitizer and Pi towards Ln3+. Benefitting from the background-free interference and highly sensitive TRL response of the sensitizer-Ln3+@surfactant probe, we achieved the rapid, selective and sensitive detection of Pi in the range of 0.5-120 µM with a limit of detection (LOD) of 0.19 µM. Furthermore, the accuracy of the proposed method based on the Ln3+ involved micelle probes was further verified through the quantitation of Pi in real biological samples.

A novel DNA methylation 10-CpG prognostic signature of disease-free survival reveal that MYBL2 is associated with high risk in prostate cancer.

BACKGROUND: Prostate cancer (PC) is the most common non-cutaneous malignancy among men in the western world. However, heterogeneity remains a pressing clinical problem. RESEARCH DESIGN AND METHODS: The least absolute shrinkage and selection operator (LASSO) was used to screen the prognostic signature. Weighted correlation network analysis (WGCNA) was used to identify the target genes associated with high-risk characteristics. Gene set enrichment analysis was used to suggest the molecular mechanism of MYBL2 in PC. In addition, in vitro experiments were carried out to validate the role of MYBL2 in PC. RESULTS: Ten DNA methylation sites were selected as the prognostic signature. A high expression of MYBL2 was associated with a poor prognosis in PC patients. The effect of MYBL2 in PC was related to KRAS, AKT, IL21, and ATM. MYBL2 facilitates the proliferation, migration, invasion, and metastasis of PC cells. CONCLUSIONS: We developed a DNA methylation 10-CpG prognostic signature to predict the prognosis of PC patients. And the high expression of MYBL2 in PC may be related to poor prognosis.

Diagnosis and Grading of Prostate Cancer by Relaxation Maps From Synthetic MRI.

BACKGROUND: The interpretation system for prostate MRI is largely based on qualitative image contrast of different tissue types. Therefore, a fast, standardized, and robust quantitative technique is necessary. Synthetic MRI is capable of quantifying multiple relaxation parameters, which might have potential applications in prostate cancer (PCa). PURPOSE: To investigate the use of quantitative relaxation maps derived from synthetic MRI for the diagnosis and grading of PCa. STUDY TYPE: Prospective. SUBJECTS: In all, 94 men with pathologically confirmed PCa or benign pathological changes. FIELD STRENGTH/SEQUENCE: T1 -weighted imaging, T2 -weighted imaging, diffusion-weighted imaging, and synthetic MRI at 3.0T. ASSESSMENT: Four kinds of tissue types were identified on pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH), and noncancerous peripheral zone (PZ). PCa foci were grouped as low-grade (LG, Gleason score ≤6) and intermediate/high-grade (HG, Gleason score ≥7). Regions of interest were manually drawn by two radiologists in consensus on parametric maps according to the pathological results. STATISTICAL TESTS: Independent sample t-test, Mann-Whitney U-test, and receiver operating characteristic curve analysis. RESULTS: T1 and T2 values of PCa were significantly lower than SH (P = 0.015 and 0.002). The differences of T1 and T2 values between PCa and noncancerous PZ were also significant (P ≤ 0.006). The area under the curve (AUC) of the apparent diffusion coefficient (ADC) value was significantly higher than T1 , T2 , and proton density (PD) values in discriminating PCa from SH and noncancerous PZ (P ≤ 0.025). T2 , PD, and ADC values demonstrated similar diagnostic performance in discriminating LG from HG PCa (AUC = 0.806 [0.640-0.918], 0.717 [0.542-0.854], and 0.817 [0.652-0.925], respectively; P ≥ 0.535). DATA CONCLUSION: Relaxation maps derived from synthetic MRI were helpful for discriminating PCa from other benign pathologies. But the overall diagnostic performance was inferior to the ADC values. T2 , PD, and ADC values performed similarly in discriminating LG from HG PCa lesions. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:552-564.

Chinese multicentre prospective registry of breast cancer patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC): a study protocol.

INTRODUCTION: Available patient-reported outcome (PRO) studies are mainly from single institution or of small sample size, and the variations across hospitals and regions were not fully analysed. A multicentre, prospective, patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC) will be planned to assess the PROs of Chinese patients with breast cancer who will undergo breast reconstruction (BR) or oncoplastic breast-conserving surgery (OBCS). METHODS AND ANALYSIS: The inclusion criteria are female patients with breast cancer aged >18 years old who will undergo BR or OBCS. This cohort will include at least 10 000 consecutive patients (about 5000 patients who will undergo BR and 5000 patients who will undergo OBCS). The exposures were surgery types: BR and OBCS regardless of the techniques and materials used. The primary endpoint will be PROs, which include BREAST-Q and quality of life (European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and EORTC QoL Breast Cancer-specific version (QLQ-BR23)). All patients will be followed up to 24 months after operations. All data will be prospectively collected using an app software. Data will be analysed using SPSS and Stata software. ETHICS AND DISSEMINATION: This study follows the Helsinki Declaration. All patients will be asked to sign an informed consent before enrolment. The results of this study will be presented at national and international meetings and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04030845; Pre-results.