CircCFL1 Promotes TNBC Stemness and Immunoescape via Deacetylation-Mediated c-Myc Deubiquitylation to Facilitate Mutant TP53 Transcription.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

CoF-DResNet: Cancer Metastasis Recognition Network based on Dynamic Coordinated Metabolic Attention and Structural Attention.

BACKGROUND: Cancer metastasis usually means that cancer cells spread to other tissues or organs, and the condition worsens. Identifying whether cancer has metastasized can help doctors infer the progression of a patient's condition and is an essential prerequisite for devising treatment plans. Fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18F -FDG PET/CT) is an advanced cancer diagnostic imaging technique that provides both metabolic and structural information. METHOD: In cancer metastasis recognition tasks, effectively integrating metabolic and structural information stands as a key technology to enhance feature representation and recognition performance. This paper proposes a cancer metastasis identification network based on dynamic coordinated metabolic attention and structural attention to address these challenges. Specifically, metabolic and structural features are extracted by incorporating a dynamic coordinated attention module (DCAM) into two branches of ResNet networks, thereby amalgamating high metabolic spatial information from PET images with texture structure information from CT images, and dynamically adjusting this process through iterations. DISCUSSION: Next, to improve the efficacy of feature expression, a multi-receptive field feature fusion module (MRFM) is included in order to execute multi-receptive field fusion of semantic features. RESULT: To validate the effectiveness of our proposed model, experiments were conducted on both a private lung lymph nodes dataset and a public soft tissue sarcomas dataset. CONCLUSION: The accuracy of our method reached 76.0% and 75.1% for the two datasets, respectively, demonstrating an improvement of 6.8% and 5.6% compared to ResNet, thus affirming the efficacy of our method.

Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation.

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

Racial and Ethnic Differences in Health Care Experiences for Veterans Receiving VA Community Care from 2016 to 2021.

BACKGROUND: Prior research documented racial and ethnic disparities in health care experiences within the Veterans Health Administration (VA). Little is known about such differences in VA-funded community care programs, through which a growing number of Veterans receive health care. Community care is available to Veterans when care is not available through the VA, nearby, or in a timely manner. OBJECTIVE: To examine differences in Veterans' experiences with VA-funded community care by race and ethnicity and assess changes in these experiences from 2016 to 2021. DESIGN: Observational analyses of Veterans' ratings of community care experiences by self-reported race and ethnicity. We used linear and logistic regressions to estimate racial and ethnic differences in community care experiences, sequentially adjusting for demographic, health, insurance, and socioeconomic factors. PARTICIPANTS: Respondents to the 2016-2021 VA Survey of Healthcare Experiences of Patients-Community Care Survey. MEASURES: Care ratings in nine domains. KEY RESULTS: The sample of 231,869 respondents included 24,306 Black Veterans (mean [SD] age 56.5 [12.9] years, 77.5% male) and 16,490 Hispanic Veterans (mean [SD] age 54.6 [15.9] years, 85.3% male). In adjusted analyses pooled across study years, Black and Hispanic Veterans reported significantly lower ratings than their White and non-Hispanic counterparts in five of nine domains (overall rating of community providers, scheduling a recent appointment, provider communication, non-appointment access, and billing), with adjusted differences ranging from - 0.04 to - 0.13 standard deviations (SDs) of domain scores. Black and Hispanic Veterans reported higher ratings with eligibility determination and scheduling initial appointments than their White and non-Hispanic counterparts, and Black Veterans reported higher ratings of care coordination, with adjusted differences of 0.05 to 0.21 SDs. Care ratings improved from 2016 to 2021, but differences between racial and ethnic groups persisted. CONCLUSIONS: This study identified small but persistent racial and ethnic differences in Veterans' experiences with VA-funded community care, with Black and Hispanic Veterans reporting lower ratings in five domains and, respectively, higher ratings in three and two domains. Interventions to improve Black and Hispanic Veterans' patient experience could advance equity in VA community care.

HMGA1 is a Prognostic Biomarker and Correlated with Glycolysis in Lung Adenocarcinoma.

Purpose: Lung cancer is one of the leading causes with high morbidity and mortality. High mobility group A1 (HMGA1) protein participates in the process of tumorigenesis. This study seeks to explore the specific role of HMGA1 in prognostic value based on The Cancer Genome Atlas (TCGA) database of Lung adenocarcinoma (LUAD) and glycolysis progression in LUAD cells. Patients and Methods: In this research, we compared HMGA1 mRNA expression between tumor tissues and normal samples and evaluated the correlations with clinical characteristics in LUAD patients based on the data of TCGA database. The survival outcome with overall survival (OS), disease-specific survival (DSS) and clinicopathologic characteristics associated were performed using the Kaplan-Meier method and Cox regression. In addition, gene-set enrichment analysis (GSEA) was carried out to explore the biological pathways that related to HMGA1. Cell experiments including cell proliferation assay and glycolysis proteins were performed with A549 and H1299 cells. Results: Our results revealed that HMGA1 mRNA expression was higher in LUAD tissues than in normal tissues. Increased HMGA1 expression in LUAD was associated with Gender (p<0.01), Pathologic stage I&II vs stage III&IV (p<0.001), T1&T2 vs T3&T4 stage (p<0.05), N0 vs N2 stage (p<0.01). Furthermore, multivariate analysis revealed that HMGA1 was an independent risk factor of OS and DSS for LUAD patients (p<0.05). HMGA1 were positively correlated with glycolysis gluconeogenesis pathway and glycolysis markers (HK2, GLUT1, PKM2, LDHA) based on GSEA and Gene Expression Profiling Interactive Analysis (GEPIA) database. At the cellular level, the results of qRT-PCR and western blot assays showed that si-HMGA1 markedly decreased the expression of glycolysis markers. HMGA1 promoted cell glycolysis progression via PI3K/AKT pathway transfected with HMGA1-plasmid and the treatment with 20 µM LY294002. Relevant animal experiments were also synchronously validated and si-HMGA1 groups down-regulated xenograft growth including the weights and size in tumor xenografts. Conclusions: In conclusion, our results suggested that HMGA1 was significantly correlated with poor survival for LUAD tissues and involved in the process of glycolysis in LUAD cells.

Imaging Intratumoral Heterogeneity of Diffuse Pancreatic Neuroendocrine Tumor With Multitracer PET/CT.

ABSTRACT: Diffuse involvement of pancreatic neuroendocrine tumor (PNET) is a rare presentation. Here, we report a case of suspected autoimmune pancreatitis with 18 F-FDG and 18 F-FAPI-42 PET/CT showing increased tracer uptake in the entire pancreas, which was eventually confirmed by biopsy pathologic analysis as diffuse PNET. 18 F-AlF-NOTA-octreotide PET/CT imaging showed heterogeneous tracer uptake in the entire pancreas.

COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer. Despite the recognized interplay between tumors and tumor-associated macrophages in fostering drug resistance and disease progression, the precise mechanisms leading these interactions remain elusive. Our study revealed that the upregulation of collagen type V alpha 1 (COL5A1) in TNBC tissues, particularly in chemoresistant samples, was closely linked to an unfavorable prognosis. Functional assays unequivocally demonstrated that COL5A1 played a pivotal role in fueling cancer growth, metastasis, and resistance to doxorubicin, both in vitro and in vivo. Furthermore, we found that the cytokine IL-6, produced by COL5A1-overexpressing TNBC cells actively promoted M2 macrophage polarization. In turn, TGFß from M2 macrophages drived TNBC doxorubicin resistance through the TGFß/Smad3/COL5A1 signaling pathway, establishing a feedback loop between TNBC cells and macrophages. Mechanistically, COL5A1 interacted with TGM2, inhibiting its K48-linked ubiquitination-mediated degradation, thereby enhancing chemoresistance and increasing IL-6 secretion. In summary, our findings underscored the significant contribution of COL5A1 upregulation to TNBC progression and chemoresistance, highlighting its potential as a diagnostic and therapeutic biomarker for TNBC.

Genetic diversity and population structure in five Inner Mongolia cashmere goat populations using whole-genome genotyping.

OBJECTIVE: As a charismatic species, cashmere goats have rich genetic resources. In the Inner Mongolia Autonomous Region, there are three cashmere goat varieties named and approved by the state. These goats are renowned for their high cashmere production and superior cashmere quality. Therefore, it is vitally important to protect their genetic resources as they will serve as breeding material for developing new varieties in the future. METHODS: Three breeds including Inner Mongolia cashmere goats (IMCG), Hanshan White cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ) were studied. IMCG were of three types: Aerbas (AEBS), Erlangshan (ELS), and Alashan (ALS). Nine DNA samples were collected for each population, and they were genomically re-sequenced to obtain high-depth data. The genetic diversity parameters of each population were estimated to determine selection intensity. Principal component analysis, phylogenetic tree construction and genetic differentiation parameter estimation were performed to determine genetic relationships among populations. RESULTS: Samples from the 45 individuals from the five goat populations were sequenced, and 30,601,671 raw single nucleotide polymorphisms (SNPs) obtained. Then, variant calling was conducted using the reference genome, and 17,214,526 SNPs were retained after quality control. Individual sequencing depth of individuals ranged from 21.13× to 46.18×, with an average of 28.5×. In the AEBS, locus polymorphism (79.28) and expected heterozygosity (0.2554) proportions were the lowest, and the homologous consistency ratio (0.1021) and average inbreeding coefficient (0.1348) were the highest, indicating that this population had strong selection intensity. Conversely, ALS and WZMQ selection intensity was relatively low. Genetic distance between HS and the other four populations was relatively high, and genetic exchange existed among the other four populations. CONCLUSION: The Inner Mongolia cashmere goat (AEBS type) population has a relatively high selection intensity and a low genetic diversity. The IMCG (ALS type) and WZMQ populations had relatively low selection intensity and high genetic diversity. The genetic distance between HS and the other four populations was relatively high, with a moderate degree of differentiation. Overall, these genetic variations provide a solid foundation for resource identification of Inner Mongolia Autonomous Region cashmere goats in the future.

Additional Findings of 18 F-AIF-FAPI-42 PET/CT in a Patient With Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma : Comparisons With 18 F-FDG PET/CT.

ABSTRACT: A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides-type cutaneous T-cell lymphoma. Staging PET with 18 F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18 F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.

A visible-light-catalyzed sulfonylation reaction of an aryl selenonium salt via an electron donor-acceptor complex.

An efficient synthesis of sulfone structures through selenonium salts and sodium sulfinates was developed. Under the irradiation of a blue LED lamp, the two substrates generate aryl and sulfonyl radicals through the activation of the intermediate electron donor acceptor (EDA) complex, thereby synthesizing aromatic, heteroaromatic and aliphatic sulfones in medium to good yields. The advantages of this strategy are metal-free, mild conditions and the leaving group is recycled to construct new selenonium salts.

Effects of game-based physical education program on enjoyment in children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to conduct a systematic review to summarize and assess the advancements lately made on the enjoyable impacts of game-based physical education interventions on children and adolescents. Additionally, it attempted to identify the effects and variables influencing the enjoyable outcomes of children and adolescents' engagement in physical education games, through meta-analysis. METHODS: This study involves a comprehensive search of different databases like Web of Science, PubMed, Embase, EBSCOhost, Cochrane, and Scopus. Specific criteria are established for the selection process to make sure the relevant literature included. The quality assessment of the included researches is conducted based on the guidelines outlined in the Cochrane 5.1 handbook. Review Manager 5.3 software is employed to synthesis the effect sizes. Additionally, bias is assessed using funnel plots, and to identify potential sources of heterogeneity, subgroup analyses are performed. RESULTS: A total of 1907 academic papers, out of which 2 articles were identified via other data sources. The present study examined the impact of a pedagogical intervention involving physical education games on the enjoyment experienced by children and adolescents. The results indicated a significant positive effect (MD = 0.53, 95%CI:[0.27,0.79], P < 0.05) of this intervention on enjoyment. Subgroup analyses further revealed that both boys (MD = 0.31, 95%CI:[0.13,0.50], P < 0.05) and girls (MD = 0.28, 95%CI:[0.05,0.51], P < 0.05) experienced increased pleasure compared to traditional physical education. Additionally, children under 12 years of age (MD = 0.41, 95%CI:[0.17,0.64], P < 0.05) benefited from sessions lasting at least 30 minutes or more per session (MD = 0.40, 95%CI:[0.19,0.60], P < 0.05), occurring 1 to 3 times per week (MD = 0.28, 95%CI:[0.16,0.40], P < 0.05), and lasting for more than 3 weeks (MD = 0.81, 95%CI:[0.29,1.34], P < 0.05). These findings suggest that the implementation of physical education games can be an effective approach to teaching this subject. CONCLUSIONS: 1) Interventions using physical games have been shown to yield beneficial outcomes in terms of enhancing the enjoyment experienced by children and adolescents. 2) The effectiveness of treatments aimed at promoting enjoyment among children and adolescents is influenced by several aspects, including gender, age, duration and frequency of physical activity, as well as the specific cycle of activity used.

LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization.

Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer.

Gallbladder's Adenocarcinoma With Enteroblastic Differentiation Revealed by 18 F-FDG PET/CT.

ABSTRACT: Gallbladder's adenocarcinoma with enteroblastic differentiation (GAED) is extremely rare. A 43-year-old woman complained of pain in the right upper abdomen, and enhanced CT showed a cystic and solid mixed mass in the hepatic hilar region. Adenocarcinoma with enteroblastic differentiation was pathologically identified. 18 F-FDG PET/CT revealed a lesion in the gallbladder neck with increased FDG uptake, accompanied by a cystic and solid mixed mass in the hepatic hilar region with liver and lymph node metastases. Gallbladder biopsy was also carried out, and GAED was confirmed. 18 F-FDG PET/CT may assist in the evaluation of GAED and guide biopsy.

18 F-FAPI-42 PET/CT Findings in a Patient With Left Ventricular Mural Thrombus.

ABSTRACT: 18 F-FAPI-42 PET/CT is a novel imaging tool targeting fibroblast activation protein (FAP). We describe the 18 F-FAPI-42 PET/CT findings of a left ventricular mural thrombus in a 50-year-old man who had chest tightness. The 18 F-FAPI-42 PET/CT showed annular uptake at the apex of the left ventricle, but there was no uptake of 18 F-FDG. This case showed that abnormal 18 F-FAPI-42 uptake in the heart may be associated with mural thrombus and should be evaluated clinically.

An extracellular humanized IFNAR immunocompetent mouse model for analyses of human interferon alpha and subtypes.

Type I interferons (IFN-Is) have key roles in immune defense and treatments for various diseases, including chronic hepatitis B virus (HBV) infection. All IFN-Is signal through a shared IFN-I heterodimeric receptor complex comprising IFN-α receptor 1 (IFNAR1) and IFNAR2 subunits, but differences in antiviral and immunomodulatory responses among IFN-I subtypes remain largely unknown. Because the IFN-IFNAR interactions are species-specific, mice exhibit weak responses to human IFN-I. To more fully characterize the actions of human IFN-α and its subtypes in vivo, a gene targeting strategy was employed to generate gene knock-in mice with extracellular-humanized IFNAR1/2 (IFNAR-hEC) in the C57BL/6N strain. IFNAR-hEC mice actively responded to human IFN-I, and endogenous mouse IFN-I signalling remained active in heterozygous mice (IfnarhEC/+). Analyses of IFNAR-hEC mice and isolated cells showed that human IFN-α2 and α14 subtypes exerted differential effect on the activation of JAK-STAT signalling and immune responses. Compared with IFN-α2, IFN-α14 induced greater activation of STAT1/2 and IFN-stimulated genes, synergistically elicited IFN-α and -γ signalling, and induced higher numbers of antigen-specific CD8+ T cells. Moreover, IFNAR-hEC mice with HBV replication displayed long-term viral suppression upon treatment with the clinically-used PEGylated hIFN-α2. These results indicate that IFNAR-hEC mice may be useful for elucidating antiviral and immunomodulatory functions of human IFN-Is and for conducting preclinical studies. A better understanding of the distinct activities of IFN-α subtypes can provide insights concerning the development of improved IFN-based therapy.

6-Shogaol prevents benzo (A) pyrene-exposed lung carcinogenesis via modulating PRDX1-associated oxidative stress, inflammation, and proliferation in mouse models.

In this study, we have investigated the chemopreventive role of 6-shogaol (6-SGL) on benzopyrene (BaP) exposed lung carcinogenesis by modulating PRDX1-associated oxidative stress, inflammation, and proliferation in Swiss albino mouse models. Mice were exposed to BaP (50 mg/kg b.wt) orally twice a week for four consecutive weeks and maintained for 16 weeks, respectively. 6-SGL (30 mg/kg b.wt) were orally administered to mouse 1 h before BaP exposure for 16 weeks. After the experiment's termination, 6-SGL (30 mg/kg b.wt) prevented the loss in body weight, increased lung weight, and the total number of tumors in the mice. Moreover, we observed that 6-SGL treatment reverted the activity of BaP-induced lipid peroxidation and antioxidants in mice. Also, 6-SGL impeded the phosphorylation of MAPK family proteins such as Erk1, p38, and Jnk1 in BaP-exposed mice. PRDX1 is an essential antioxidant protein that scavenges toxic radicals and enhances several antioxidant proteins. Overexpression of PRDX1 substantially inhibits MAPKs, proliferation, and inflammation signaling axis. Hence, PRDX1 is thought to be a novel targeting protein for preventing BaP-induced lung cancer. In this study, we have obtained the 6-SGL treatment in a mouse model that reverted BaP-induced depletion of PRDX1 expression. Moreover, pretreatment of 6-SGL (30 mg/kg b.wt) significantly inhibited enhanced proinflammatory cytokines (TNF-α, IL-6, IL-ß1, IL-10) and proliferative markers (Cyclin-D1, Cyclin-D2, and PCNA) in BaP-exposed mice. The histopathological studies also confirmed that 6-SGL effectively protected the cells with less damage. Thus, the study demonstrated that 6-SGL could be a potential phytochemical and act as a chemopreventive agent in BaP-induced lung cancer by enhancing PRDX1 expression.

Establishment of machine learning-based tool for early detection of pulmonary embolism.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a complex disease with high mortality and morbidity rate, leading to increasing society burden. However, current diagnosis is solely based on symptoms and laboratory data despite its complex pathology, which easily leads to misdiagnosis and missed diagnosis by inexperienced doctors. Especially, CT pulmonary angiography, the gold standard method, is not widely available. In this study, we aim to establish a rapid and accurate screening model for pulmonary embolism using machine learning technology. Importantly, data required for disease prediction are easily accessed, including routine laboratory data and medical record information of patients. METHODS: We extracted features from patients' routine laboratory results and medical records, including blood routine, biochemical group, blood coagulation routine and other test results, as well as symptoms and medical history information. Samples with a feature loss rate greater than 0.8 were deleted from the original database. Data from 4723 cases were retained, 231 of which were positive for pulmonary embolism. 50 features were retained through the positive and negative statistical hypothesis testing which was used to build the predictive model. In order to avoid identification as majority-class samples caused by the imbalance of sample proportion, we used the method of Synthetic Minority Oversampling Technique (SMOTE) to increase the amount of information on minority samples. Five typical machine learning algorithms were used to model the screening of pulmonary embolism, including Support Vector Machines, Logistic Regression, Random Forest, XGBoost, and Back Propagation Neural Networks. To evaluate model performance, sensitivity, specificity and AUC curve were analyzed as the main evaluation indicators. Furthermore, a baseline model was established using the characteristics of the pulmonary embolism guidelines as a comparison model. RESULTS: We found that XGBoost showed better performance compared to other models, with the highest sensitivity and specificity (0.99 and 0.99, respectively). Moreover, it showed significant improvement in performance compared to the baseline model (sensitivity and specificity were 0.76 and 0.76 respectively). More important, our model showed low missed diagnosis rate (0.46) and high AUC value (0.992). Finally, the calculation time of our model is only about 0.05 s to obtain the possibility of pulmonary embolism. CONCLUSIONS: In this study, five machine learning classification models were established to assess the likelihood of patients suffering from pulmonary embolism, and the XGBoost model most significantly improved the precision, sensitivity, and AUC for pulmonary embolism screening. Collectively, we have established an AI-based model to accurately predict pulmonary embolism at early stage.

PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: The protein tyrosine phosphatase H receptor (PTPRH) is known to regulate the occurrence and development of pancreatic and colorectal cancer. However, its association with glycolysis in non-small cell lung cancer (NSCLC) is still unclear. In this study, we aimed to investigate the relationship between PTPRH expression and glucose metabolism and the underlying mechanism of action. METHODS: The expression of PTPRH in NSCLC cells was evaluated by IHC staining, qRT‒PCR and Western blotting. The effect of PTPRH on cell biological behavior was evaluated by colony assays, EdU experiments, Transwell assays, wound healing assays and flow cytometry. Changes in F-18-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolite levels after altering PTPRH expression were detected via a gamma counter and lactic acid tests. The expression of glycolysis-related proteins in NSCLC cells was detected by Western blotting after altering PTPRH expression. RESULTS: The results showed that PTPRH was highly expressed in clinical patient tissue samples and closely related to tumor diameter and clinical stage. In addition, PTPRH expression was associated with glycometabolism indexes on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging, the expression level of Ki67 and the expression levels of glycolysis-related proteins. PTPRH altered cell behavior, inhibited apoptosis, and promoted 18F-FDG uptake, lactate production, and the expression of glycolysis-related proteins. In addition, PTPRH modulated the glycometabolism of NSCLC cells via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, as assessed using LY294002 and 740Y-P (an inhibitor and agonist of PI3K, respectively). The same results were validated in vivo using a xenograft tumor model in nude mice. Protein expression levels of PTPRH, glycolysis-related proteins, p-PI3K/PI3K and p-AKT/AKT were measured by IHC staining using a subcutaneous xenograft model in nude mice. CONCLUSIONS: In summary, we report that PTPRH promotes glycolysis, proliferation, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in NSCLC and ultimately promotes tumor progression, which can be regulated by LY294002 and 740Y-P. These results suggest that PTPRH is a potential therapeutic target for NSCLC.

Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition).

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."