Using multimodal ultrasound including full-time-series contrast-enhanced ultrasound cines for identifying the nature of thyroid nodules.

Background: Based on the conventional ultrasound images of thyroid nodules, contrast-enhanced ultrasound (CEUS) videos were analyzed to investigate whether CEUS improves the classification accuracy of benign and malignant thyroid nodules using machine learning (ML) radiomics and compared with radiologists. Materials and methods: The B-mode ultrasound (B-US), real-time elastography (RTE), color doppler flow images (CDFI) and CEUS cines of patients from two centers were retrospectively gathered. Then, the region of interest (ROI) was delineated to extract the radiomics features. Seven ML algorithms combined with four kinds of radiomics data (B-US, B-US + CDFI + RTE, CEUS, and B-US + CDFI + RTE + CEUS) were applied to establish 28 models. The diagnostic performance of ML models was compared with interpretations from expert and nonexpert readers. Results: A total of 181 thyroid nodules from 181 patients of 64 men (mean age, 42 years +/- 12) and 117 women (mean age, 46 years +/- 12) were included. Adaptive boosting (AdaBoost) achieved the highest area under the receiver operating characteristic curve (AUC) of 0.89 in the test set among 28 models when combined with B-US + CDFI + RTE + CEUS data and an AUC of 0.72 and 0.66 when combined with B-US and B-US + CDFI + RTE data. The AUC achieved by senior and junior radiologists was 0.78 versus (vs.) 0.69 (p > 0.05), 0.79 vs. 0.64 (p < 0.05), and 0.88 vs. 0.69 (p < 0.05) combined with B-US, B-US+CDFI+RTE and B-US+CDFI+RTE+CEUS, respectively. Conclusion: With the addition of CEUS, the diagnostic performance was enhanced for all seven classifiers and senior radiologists based on conventional ultrasound images, while no enhancement was observed for junior radiologists. The diagnostic performance of ML models was similar to senior radiologists, but superior to those junior radiologists.

Corrigendum: Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: from static images to CEUS video analysis.

[This corrects the article DOI: 10.3389/fonc.2022.951973.].

Non-symmetric stapling of native peptides.

Stapling has emerged as a powerful technique in peptide chemistry. It enables precise control over peptide conformation leading to enhanced properties such as improved stability and enhanced binding affinity. Although symmetric stapling methods have been extensively explored, the field of non-symmetric stapling of native peptides has received less attention, largely as a result of the formidable challenges it poses - in particular the complexities involved in achieving the high chemo-selectivity and site-selectivity required to simultaneously modify distinct proteinogenic residues. Over the past 5 years, there have been significant breakthroughs in addressing these challenges. In this Review, we describe the latest strategies for non-symmetric stapling of native peptides, elucidating the protocols, reaction mechanisms and underlying design principles. We also discuss current challenges and opportunities this field offers for future applications, such as ligand discovery and peptide-based therapeutics.

Diagnostic significance of cerebrospinal fluid flow cytometry in Chinese children with B lineage acute lymphoblastic leukemia.

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.

Copper-Catalyzed Asymmetric Remote C(sp3)-H Alkylation of N-Fluorocarboxamides with Glycine Derivatives and Peptides.

Saturated hydrocarbon bonds are ubiquitous in organic molecules; to date, the selective functionalization of C(sp3)-H bonds continues to pose a notorious difficulty, thereby garnering significant attention from the synthetic chemistry community. During the past several decades, a wide array of powerful new methodologies has been developed to enantioselectively modify C(sp3)-H bonds that is successfully applied in asymmetric formation of diverse bonds, including C-C, C-N, and C-O bonds; nevertheless, the asymmetric C(sp3)-H alkylation is elusive and, therefore, far less explored. In this work, we report a direct and robust strategy to construct highly valuable enantioenriched unnatural α-amino acid (α-AA) cognates and peptides by a copper-catalyzed enantioselective remote C(sp3)-H alkylation of N-fluorocarboxamides and readily accessible glycine esters under ambient conditions. The key to success lies in the optically active Cu catalyst generated through the coordination of glycine derivatives to enantiopure bisphosphine/Cu(I) species, which is beneficial to the single electronic reduction of N-fluorocarboxamides and the subsequent stereodetermining alkylation. More importantly, all types (primary, secondary, tertiary, and even α-oxy) of δ-C(sp3)-H bonds could be site- and stereospecifically activated by the kinetically favored 1,5-hydrogen atom transfer (1,5-HAT) step.

MRI- and DWI-Based Radiomics Features for Preoperatively Predicting Meningioma Sinus Invasion.

The aim of this study was to use multimodal imaging (contrast-enhanced T1-weighted (T1C), T2-weighted (T2), and diffusion-weighted imaging (DWI)) to develop a radiomics model for preoperatively predicting venous sinus invasion in meningiomas. This prediction would assist in selecting the appropriate surgical approach and forecasting the prognosis of meningiomas. A retrospective analysis was conducted on 331 participants who had been pathologically diagnosed with meningiomas. For each participant, 3948 radiomics features were acquired from the T1C, T2, and DWI images. Minimum redundancy maximum correlation, rank sum test, and multi-factor recursive elimination were used to extract the most significant features of different models. Then, multivariate logistic regression was used to build classification models to predict meningioma venous sinus invasion. The diagnostic capabilities were assessed using receiver operating characteristic (ROC) analysis. In addition, a nomogram was constructed by incorporating clinical and radiological characteristics and a radiomics signature. To assess the clinical usefulness of the nomogram, a decision curve analysis (DCA) was performed. Tumor shape, boundary, and enhancement features were independent predictors of meningioma venous sinus invasion (p = 0.013, p = 0.013, p = 0.005, respectively). Eleven (T2:1, T1C:4, DWI:6) of the 3948 radiomics features were screened for strong association with meningioma sinus invasion. The areas under the ROC curves for the training and external test sets were 0.946 and 0.874, respectively. The clinicoradiomic model showed excellent predictive performance for invasive meningioma, which may help to guide surgical approaches and predict prognosis.

The vinyl sulfone motif as a structural unit for novel drug design and discovery.

INTRODUCTION: Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted. AREA COVERED: In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design. EXPERT OPINION: Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.

α-Lipoic acid chemistry: the past 70 years.

α-Lipoic acid (ALA) is a naturally occurring sulfur-containing fatty acid with high antioxidant activity. It is also used to treat diabetes, nerve pain, weight loss, heart disease, and primary mitochondrial disorders. Moreover, numerous therapeutic agents have been studied for managing other clinical conditions, including for anticancer, anti-HIV, anti-inflammatory, and anti-AD treatments. The medicinal importance of ALA, especially its biologically active form (R-ALA), has attracted considerable attention from synthetic chemists in industrial and academic fields. In this review, we discuss synthetic approaches to ALA and R-ALA over the past 70 years (1952 to the present), which will help medicinal chemists further develop novel routes for their synthesis.

Analysis of mental health status and related factors in patients with acute cerebral infarction.

BACKGROUND: Acute cerebral infarction (ACI) is characterized by a high incidence of morbidity, disability, recurrence, death and heavy economic burden, and has become a disease of concern in global researchers. As ACI has serious effects on patients' physical status, life and economy, often causing anxiety, depression and other psychological problems, these problems can lead to the aggravation of physical symptoms; thus, it is very important to understand the factors affecting the mental health of these patients. AIM: To understand the elements that affect the mental health of patients who have suffered an ACI. METHODS: A questionnaire survey was conducted among patients with ACI admitted to three tertiary hospitals (Quanzhou First Hospital, Fuqing City Hospital Affiliated to Fujian Medical University, and the 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China) in Fujian Province from January 2022 to December 2022 using the convenience sampling method. ACI inpatients who met the inclusion criteria were selected. Informed consent was obtained from the patients before the investigation, and a face-to-face questionnaire survey was conducted using a unified scale. The questionnaire included a general situation questionnaire, Zung's self-rating depression scale and Zung's self-rating anxiety scale. All questionnaires were checked by two researchers and then the data were input and sorted using Excel software. The general situation of patients with ACI was analyzed by descriptive statistics, the influence of variables on mental health by the independent sample t test and variance analysis, and the influencing factors on psychological distress were analyzed by multiple stepwise regression. RESULTS: The average age of the 220 patients with ACI was 68.64 ± 10.74 years, including 142 males and 78 females. Most of the patients were between 60 and 74 years old, the majority had high school or technical secondary school education, most lived with their spouse, and most lived in cities. The majority of patients had a personal income of 3001 to 5000 RMB yuan per month. The new rural cooperative medical insurance system had the largest number of participants. Most stroke patients were cared for by their spouses and of these patients, 52.3% had previously smoked. Univariate analysis showed that gender, age, residence, course of disease, number of previous chronic diseases and smoking history were the main factors affecting the anxiety scores of patients with ACI. Age, living conditions, monthly income, course of disease and knowledge of disease were the primary variables influencing the depression score in patients with ACI. The findings of multivariate analysis revealed that the course of disease and gender were the most important factors influencing patients' anxiety scores, and the course of disease was also the most important factor influencing patients' depression scores. CONCLUSION: Long disease course and female patients with ACI were more likely to have psychological problems such as a high incidence of emotional disorders. These groups require more attention and counseling.

Hypoglossal nerve delineation in nasopharyngeal carcinoma patients may reduce the radiation dose and damage to the nerve.

This study aims to establish a delineation guideline for the contouring of the hypoglossal nerve by dividing the nerve into different segments, and to test the possibility of a radiation dose reduction to the hypoglossal nerve in NPC patients receiving radiotherapy. Twenty NPC patients were selected arbitrarily. The hypoglossal nerves were delineated using anatomic landmarks and divided into the cisternal, intracanalicular, carotid, and transverse segments. The tumor coverage by radiation and dose-volume parameters of the nerve with and without various dose constraints to the hypoglossal nerve were compared. The hypoglossal nerve, which is invisible on CT images, can be delineated accurately with the assistance of several anatomic landmarks. Without a dose constraint to the hypoglossal nerve, the carotid space, intracanalicular, and transverse segments had high radiation dose-volumes. The dose-volume to the nerve, however, can be reduced when the nerve was defined and a dose constraint was given. The delineation of the hypoglossal nerve with its different segments is feasible. The carotid space, intracanalicular, and transverse segments received the highest dose, where the nerve damage was most likely located. The dose to the nerve can be reduced to less than 70 Gy using the intensity-modulated radiotherapy technique.

Design of Balanced Cyclooxygenase Inhibitors Based on Natural Anti-inflammatory Ascidian Metabolites and Celecoxib.

The serious adverse effects caused by non-selective and selective cyclooxygenase-2 (COX-2) inhibitors remain significant concerns for current anti-inflammatory drugs. In this study, we present the design and synthesis of a novel series of celecoxib analogs incorporating a hydrazone linker, which were subjected to in silico analysis to compare their binding poses with those of clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) against COX-1 and COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX enzymes, and compound 6 m, exhibiting potent balanced inhibition, was selected for subsequent in vitro anti-inflammatory assays. Treatment with 6 m effectively suppressed the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, resulting in reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, as well as decreased production of prostaglandin E2 (PGE2 ), nitric oxide (NO), and reactive oxygen species (ROS). However, 6 m has no effect on the MAPK signaling pathway. Therefore, due to its potent in vitro anti-inflammatory activity coupled with lack of cytotoxicity, 6 m represents a promising candidate for further development as a new lead compound targeting inflammation.

[Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. METHODS: The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. RESULTS: A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. CONCLUSION: Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.

[Pollution Characteristics, Source Analysis, and Risk Assessment of Heavy Metals in the Surrounding Farmlands of Manganese Mining Area].

In order to understand the status of heavy metal pollution and the resulting ecological risk of farmland soil surrounding the manganese mining area, 174 soil samples were collected, and the heavy metals(Cu, Zn, Pb, Cr, Ni, Mn, As, and Hg) were analyzed. Principal component analysis (PCA) and the positive matrix factorization (PMF) model were used to determine the source of heavy metals in the soils. The single-factor pollution index method, geo-accumulation index method, potential ecological risk assessment method, and US EPA health risk assessment model were used to evaluate the ecological environment risk of heavy metals. The results showed that the average values of Cu, Zn, Cr, Ni, Mn, and Hg exceeded the background value of Guizhou. 100% of Zn samples and 38.86% of Cu samples exceeded the risk screening value for agricultural land soil pollution. Source analysis revealed that the main sources of soil heavy metals were mining emission, mixed agricultural activity and transportation, nature, and agricultural activities. The risk evaluation showed that Ni, Cr, Pb, and As belonged to the clean level, Hg and Cu were in a light pollution stage, Zn fell into the category of moderate contamination, and Mn reached the heavy pollution level. Cu, Zn, Pb, Cr, Ni, Mn, As, and Cd posed low potential ecological risk, while Hg caused a considerable potential ecological risk. In total, the integrated potential ecological risk of heavy metals was ranked "strong", eight types of heavy metals had carcinogenic risks and non-carcinogenic risks for children aged 0-5 years, and the main contributing factors were Cr and Mn, respectively.

Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.

Background: Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. Bone erosion is the most serious pathological condition of RA and the main cause of joint deformities and disability. Melittin acupoint injection (MAI) is an effective traditional Chinese medicine (TCM) method for RA treatment. This study aimed to investigate the effect of MAI on RA bone erosion and to elucidate the underlying mechanism. Methods: A collagen-induced arthritis (CIA) mouse model was established as the experimental subject. MAI was administrated once every other day for 28 days to mice with CIA. The effects of MAI on joint diseases were assessed by body weight, arthritis index (AI) score, swollen joint count (SJC) score, and hind paw thickness. Ankle radiological changes were captured by micro-computed tomography (micro-CT) and histological changes were observed by pathological staining. Organ histological changes, spleen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Crea) levels of serum were tested to evaluate the toxicity of MAI. Cytokine expression levels were confirmed by enzyme-linked immunosorbent assay (ELISA) to evaluate the immunity of CIA mice. Results: MAI administration markedly improved the clinical signs of CIA in mice, including hind paw thickness, AI, and the number of swollen paw joints (most of them P<0.05 or even <0.01). According to histopathological analysis, MAI ameliorated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone erosion (all P<0.01). Micro-CT and tartrate-resistant acid phosphatase (TRAP) staining (P<0.01) also revealed that MAI could relieve bone erosion via reducing the formation of osteoclasts. Not only could MAI relieve the immunological boost [P<0.05 for the high-dose MAI (HM) group], but also it had no liver or kidney side effects (P>0.05). In addition, it decreased the serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) and increased the serum levels of IL-4 and IL-10 (the majority of P<0.05 or even <0.01). Transcriptome sequencing results indicated that MAI affected the expression of osteoclast differentiation pathway genes, which was connected with the receptor activator of the nuclear factor κB ligand/nuclear factor kappa B (RANKL/NF-κB) pathway. Conclusions: Based on our findings, MAI could suppress joint inflammation and inhibit RANKL/NF-κB-mediated osteoclast differentiation to rescue bone erosion in CIA mice, suggesting that MAI can be a potentially therapeutic substance for RA.

MiR-497-3p induces Premature ovarian failure by targeting KLF4 to inactivate Klotho/PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Premature ovarian failure (POF), as a gynecological endocrine disease, features the manifestation of irregular menstruation, amenorrhea, infertility and perimenopausal syndrome. MicroRNAs (miRNAs) have been reported to modulate POF. However, the specific regulatory mechanism of miR-497-3p in POF remain unclear. METHODS: Quantitative reverse transcription-PCR (RT-qPCR) and western blot were implemented to analyze RNA and protein levels, respectively. Comet assay was performed for the detection of DNA damage. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis of CTX-induced KGN cell (POF cell model). Bioinformatics was utilized to screen out the downstream mRNAs potentially regulated by miR-497-3p. Chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and RNA pulldown assays were performed to demonstrate the interaction between miR-497-3p and Kruppel-like factor 4 (KLF4) or between KLF4 and Klotho (KL). Rescue assays were performed to verify the involvement of Klotho in miR-497-3p-mediated functions of POF cell model. RESULTS: MiR-497-3p was upregulated in CTX-treated KGN cells. Knockdown of miR-497-3p could reverse the promoting effects of CTX on DNA damage and cell apoptosis. MiR-497-3p negatively regulated Klotho expression by directly targeting the transcription activator KLF4. KLF4 activated Klotho transcription. MiR-497-3p inactivated PI3K/AKT/mTOR signaling pathway through KLF4/Klotho axis. Klotho knockdown reversed the effects of MiR-497-3p on the functions of POF cell model. CONCLUSION: MiR-497-3p promotes DNA damage and apoptosis in CTX-treated KGN cells by targeting KLF4 to downregulate Klotho and inactivate the PI3K/AKT/mTOR signaling pathway. This study unveils novel mechanisms associated with cell functional changes in POF and may enrich therapeutic strategy for POF.

Design, synthesis fusidic acid derivatives alleviate acute lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway.

Acute lung injury (ALI) refers to a series of lung lesions resulting from multiple lung injuries, even leading to morbidity and death, abundant previous reports have showed that anti-inflammatory as a key to treatment of ALI. Fusidic acid (FA) as an antibiotic has significant anti-bacterial activity and anti-inflammatory effects. In this study, we designed and synthesized 34 FA derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide (LPS)-induced RAW264.7 cells to evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO) and interleukin-6 (IL-6). Most of compounds showed inhibitory effects on inflammatory NO and IL-6 in LPS-induced RAW264.7 cells. Based on the screening results, compound a1 showed the strongest anti-inflammatory activity. Compared with FA, the inhibition rate NO and IL-6 of compound a1 increased 3.08 and 2.09 times at 10 µM, respectively. We further measured a1 inhibited inflammatory factor NO (IC50 = 3.26 ± 0.42 µM), IL-6 (IC50 = 1.85 ± 0.21 µM) and TNF-α (IC50 = 3.88 ± 0.55 µM). We also demonstrated that a1 markedly inhibits the expression of certain immune-related cytotoxic factors, including cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS). In vivo results indicate that a1 can reduce lung inflammation and NO, IL-6, TNF-α, COX-2 and iNOS in LPS-induced ALI mice. On the one hand, we demonstrated a1 inhibits the mitogen-activated protein kinase (MAPK) signaling pathway by down-regulating the phosphorylation of p38 MAPK, c-Jun N-terminal kinase (c-JNK) and extracellular signal-regulated kinase (ERK). Moreover, a1 also suppressing the phosphorylation of inhibitory NF-κB inhibitor α (IκBα) inhibits the activation of the nuclear factor-κB (NF-κB) signaling pathway. On the other hand, we demonstrated a1 also role in anti-inflammatory by inhibits nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and further inhibits Caspase-1 and inflammatory factor interleukin-1ß (IL-1ß). In conclusion, our study demonstrates that a1 has an anti-inflammatory effect and alleviates ALI by regulating inflammatory mediators and suppressing the MAPK, NF-κB and NLRP3 inflammasome signaling pathways.

Multimodal ultrasound features of breast cancers: correlation with molecular subtypes.

OBJECTIVES: To investigate whether multimodal intratumour and peritumour ultrasound features correlate with specific breast cancer molecular subtypes. METHODS: From March to November 2021, a total of 85 patients with histologically proven breast cancer underwent B-mode, real-time elastography (RTE), colour Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The time intensity curve (TIC) of CEUS was obtained, and the peak and time to peak (TTP) were analysed. Chi-square and binary logistic regression were used to analyse the connection between multimodal ultrasound imaging features and breast cancer molecular subtype. RESULTS: Among 85 breast cancers, the subtypes were as follows: luminal A (36 cases, 42.4%), luminal B (20 cases, 23.5%), human epidermal growth factor receptor-2 positive (HER2+) (16 cases, 18.8%), and triple negative breast cancer (TNBC) (13 cases, 15.3%). Binary logistic regression models showed that RTE (P < 0.001) and CDFI (P = 0.036) were associated with the luminal A cancer subtype (C-index: 0.741), RTE (P = 0.016) and the peak ratio between intratumour and corpus mamma (P = 0.036) were related to the luminal B cancer subtype (C-index: 0.788). The peak ratio between peritumour and intratumour (P = 0.039) was related to the HER2 + cancer subtype (C-index: 0.859), and CDFI (P = 0.002) was associated with the TNBC subtype (C-index: 0.847). CONCLUSIONS: Multimodal ultrasound features could be powerful predictors of specific breast cancer molecular subtypes. The intra- and peritumour CEUS features play assignable roles in separating luminal B and HER2 + breast cancer subtypes.

CircCCNB1 Knockdown Blocks the Progression of Cervical Cancer by Acting as Competing Endogenous RNA in the miR-370-3p/SOX4 Pathway.

OBJECTIVE: Cervical cancer is one of the leading causes of cancer-related death in women, which has been shown to be associated with the deregulation of circular RNAs (circRNAs). The aim of this study was to determine the role of circRNA cyclin B1 (circCCNB1) in cervical cancer. METHODS: The expression of circCCNB1, microRNA-370-3p (miR-370-3p), and SRY-box transcription factor 4 (SOX4) mRNA was detected by quantitative real-time PCR (qPCR). Functional experiments, including colony formation assay, EdU assay, transwell assay and flow cytometry assay, were performed. Lactate production and glucose uptake were examined to assess glycolysis metabolism. The protein levels of glycolysis-related markers and SOX4 were detected by western blot. The interaction between miR-370-3p and circCCNB1 or SOX4 was verified by dual-luciferase reporter, RIP, and pull-down assay. Xenograft assay was performed to monitor the role of circCCNB1 in animal models. RESULTS: CircCCNB1 was highly expressed in cervical cancer tissues and cells (squamous cell carcinoma and adenocarcinoma cells). The knockdown of circCCNB1 inhibited cell proliferation, migration, invasion and glycolysis metabolism, and induced cell apoptosis. CircCCNB1 functioned as miR-370-3p sponge to suppress miR-370-3p expression and function. Moreover, circCCNB1 inhibited the expression of miR-370-3p to increase the expression of SOX4. MiR-370-3p inhibition reversed the effects of circCCNB1 knockdown and thus promoted cell proliferation, migration, invasion and glycolysis. SOX4 overexpression reversed the effects of miR-370-3p restoration and thus promoted cell proliferation, migration, invasion and glycolysis. CONCLUSION: CircCCNB1 knockdown blocks cervical cancer development by targeting the miR-370-3p/SOX4 pathway.

Comparison of anti-tumor activities and underlying mechanisms of glucuronomannan oligosaccharides and its sulfated derivatives on the hepatocarcinoma Huh7.5 cells.

Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro, and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates.

A nomogram based on combining clinical features and contrast enhanced ultrasound is not able to identify Her-2 over-expressing cancer from other breast cancers.

Objective: The aim of this study was to evaluate whether a predictive model based on a contrast enhanced ultrasound (CEUS)-based nomogram and clinical features (Clin) could differentiate Her-2-overexpressing breast cancers from other breast cancers. Methods: A total of 152 pathology-proven breast cancers including 55 Her-2-overexpressing cancers and 97 other cancers from two units that underwent preoperative CEUS examination, were included and divided into training (n = 102) and validation cohorts (n = 50). Multivariate regression analysis was utilized to identify independent indicators for developing predictive nomogram models. The area under the receiver operating characteristic (AUC) curve was also calculated to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared. Results: In the training cohort, 7 clinical features (menstruation, larger tumor size, higher CA153 level, BMI, diastolic pressure, heart rate and outer upper quarter (OUQ)) + enlargement in CEUS with P < 0.2 according to the univariate analysis were submitted to the multivariate analysis. By incorporating clinical information and enlargement on the CEUS pattern, independently significant indicators for Her-2-overexpression were used for further predictive modeling as follows: Model I, nomogram model based on clinical features (Clin); Model II, nomogram model combining enlargement (Clin + Enlargement); Model III, nomogram model based on typical clinical features combining enlargement (MC + BMI + diastolic pressure (DP) + outer upper quarter (OUQ) + Enlargement). Model II achieved an AUC value of 0.776 at nomogram cutoff score value of 190, which was higher than that of the other models in the training cohort without significant differences (all P>0.05). In the test cohort, the diagnostic efficiency of predictive model was poor (all AUC<0.6). In addition, the sensitivity and specificity were not significantly different between Models I and II (all P>0.05), in either the training or the test cohort. In addition, Clin exhibited an AUC similar to that of model III (P=0.12). Moreover, model III exhibited a higher sensitivity (70.0%) than the other models with similar AUC and specificity, only in the test cohort. Conclusion: The main finding of the study was that the predictive model based on a CEUS-based nomogram and clinical features could not differentiate Her-2-overexpressing breast cancers from other breast cancers.