Trends and projection of burden on lung cancer and risk factors in China from 1990 to 2060.

BACKGROUND: Lung cancer (LC) is currently the number one malignancy death rate disease in China, and its disease burden is serious. The study aimed to analyze trends of LC and its risk factor attributable disease in China from 1990 to 2019 and predict the next 41 years. METHODS: The average annual percentage change (AAPC) was used to analyze the trend of LC and its risk factor attributable incidence, deaths, and disability-adjusted life years (DALYs) rate in China from 1990 to 2019, collected in the Global Burden of Disease 2019. Cochran-Armitage trends examine trends in lung cancer disease burden by sex, age, and attributable risk factor groups in China from 1990 to 2019. In addition, based on data on death and DALYs rate due to LC and its risk factors between 1990 and 2019, an autoregressive integrated moving average (ARIMA) model was developed to predict the change in the trend of burden of disease due to LC and its risk factors over the next 41 years, and the model was evaluated using the model parameters root mean square error, mean absolute error, and mean absolute percentage error. RESULTS: From 1990 to 2019, the incidence, mortality and DALYs of LC were all increased. Among the eight risk factors associated with lung cancer, the DALYs rate and mortality rate of lung cancer risk factors for Chinese residents increased from 1990 to 2019, except for household air pollution from solid fuels and diet low in fruit, which showed a decrease; among them, the DALYs rate and mortality rate due to ambient particulate matter pollution showed the greatest increase with AAPC values of 2.880 and 3.310, respectively, while DALYs and mortality rates due to household air pollution from solid fuels showed the largest decreases, with AAPC values of -4.755 and -4.348, respectively. The results of the ARIMA model predictions show that both the mortality rate and the rate of DALYs for lung cancer are increasing yearly, and it is predicted that the rate of DALYs for lung cancer by 2060 will reach 740.095/100 000 and the mortality rate will reach 35.151/100 000. It is expected that by 2060, the top four risk factors for lung cancer in China will be, in order of DALYs rate and mortality rate, smoking, ambient particulate matter pollution, high fasting plasma glucose (HFPG), and secondhand smoke, with HFPG showing the greatest increase. CONCLUSIONS: The LC burden increased from 1990 to 2019 in China, the LC burden that could be attributed to HFPG will continue to increase in the next 40 years, and will be the third most factor by 2060. Targeted interventions are warranted to facilitate the prevention of LC and improvement of health-related quality of life patients with LC.

Imaging findings of Epstein-Barr Virus-positive inflammatory follicular dendritic cell sarcoma of spleen: A case report.

BACKGROUND: Spleen Epstein-Barr Virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (FDCS) is rare, and the imaging signs are unclear. The COVID-19 has been confirmed to be the cause of pneumonia and can cause a variety of diseases including myocarditis. However, it has not been reported to be the cause of the exacerbation or activation of EBV-positive inflammatory FDCS. OBJECTIVE: The objective is to extract the imaging features of EBV-positive inflammatory FDCS in the spleen and analyze the reasons for the special features of this case. METHODS: By analyzing the patient's treatment process and imaging examinations (A 77-year-old female was admitted to the hospital due to generalized discomfort and pain symptoms. When she was admitted to the hospital a year earlier with COVID-19 pneumonia, a chest CT scan showed that she had a splenic tumor. During this admission, CT scans showed two irregularly shaped and unevenly dense soft tissue density masses within the spleen, with uneven enhancement on contrast-enhanced im-aging within the solid components and along the edges. PET/CT scans revealed elevated glucose metabolism in the masses. Postoperative pathological diagnosis confirmed splenic EBV-positive inflammatory FDCS.), reading the literature, sorting out the disease cognitive process, epidemiology, and pathological data of EBV-positive inflammatory FDCS, we discussed the imaging manifestations and possible differential diagnosis of the disease. RESULTS: The patient was finally diagnosed with splenic EBV-positive inflammatory FDCS. CONCLUSIONS: Imaging features of EBV-positive inflammatory FDCS in the spleen include a high incidence of hemorrhage and necrosis, persistent moderate enhancement of the solid portion, a "capsular-like enhancement" structure at the tumor edge, and possibly active glucose metabolism with high Standardized Uptake Values (SUVs). COVID-19 infection and long-term COVID-19 sequelae may exacerbate and activate EBV-positive inflammatory FDCS in the spleen, and the mechanism remains to be further studied.

Optimizing predictions: improved performance of preoperative gadobenate-enhanced MRI hepatobiliary phase features in predicting vessels encapsulating tumor clusters in hepatocellular carcinoma-a multicenter study.

BACKGROUND: Vessels Encapsulating Tumor Clusters (VETC) are now recognized as independent indicators of recurrence and overall survival in hepatocellular carcinoma (HCC) patients. However, there has been limited investigation into predicting the VETC pattern using hepatobiliary phase (HBP) features from preoperative gadobenate-enhanced MRI. METHODS: This study involved 252 HCC patients with confirmed VETC status from three different hospitals (Hospital 1: training set with 142 patients; Hospital 2: test set with 64 patients; Hospital 3: validation set with 46 patients). Independent predictive factors for VETC status were determined through univariate and multivariate logistic analyses. Subsequently, these factors were used to construct two distinct VETC prediction models. Model 1 included all independent predictive factors, while Model 2 excluded HBP features. The performance of both models was assessed using the Area Under the Curve (AUC), Decision Curve Analysis, and Calibration Curve. Prediction accuracy between the two models was compared using Net Reclassification Improvement (NRI) and Integrated Discriminant Improvement (IDI). RESULTS: CA199, IBIL, shape, peritumoral hyperintensity on HBP, and arterial peritumoral enhancement were independent predictors of VETC. Model 1 showed robust predictive performance, with AUCs of 0.836 (training), 0.811 (test), and 0.802 (validation). Model 2 exhibited moderate performance, with AUCs of 0.813, 0.773, and 0.783 in the respective sets. Calibration and decision curves for both models indicated consistent predictions between predicted and actual VETC, benefiting HCC patients. NRI showed Model 1 increased by 0.326, 0.389, and 0.478 in the training, test, and validation sets compared to Model 2. IDI indicated Model 1 increased by 0.036, 0.028, and 0.025 in the training, test, and validation sets compared to Model 2. CONCLUSION: HBP features from preoperative gadobenate-enhanced MRI can enhance the predictive performance of VETC in HCC.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.

Aging Increases Global Annual Food Greenhouse Gas Emissions up to 300 Million Tonnes by 2100.

The dietary preferences of the elderly population exhibit distinct variations from the overall averages in most countries, gaining increasing significance due to aging demographics worldwide. These dietary preferences play a crucial role in shaping global food systems, which will result in changed environmental impacts in the future such as greenhouse gas (GHG) emissions. We present a quantitative evaluation of the influence of population aging on the changes in GHG emissions from global food systems. To achieve this, we developed regional dietary coefficients (DCs) of the elderly based on the Global Dietary Database (GDD). We then reconciled the GDD with the dataset from the Food and Agriculture Organization of the United Nations (FAO) to calculate the food GHG emissions of the average population in each of the countries. By applying the DCs, we estimated the national food GHG emissions and obtained the variations between the emissions from aged and average populations. We employed a modified version of the regional integrated model of climate and the economy model (RICE) to forecast the emission trends in different countries based on FAO and GDD data. This integrated approach allowed us to evaluate the dynamic relationships among aging demographics, food consumption patterns, and economic developments within regions. Our results indicate that the annual aging-embodied global food GHG emissions will reach 288 million tonnes of CO2 equivalent (Mt CO2e) by 2100. This estimation is crucial for policymakers, entrepreneurs, and researchers as it provides insights into a potential future environmental challenge and emphasizes the importance of sustainable food production and consumption strategies to GHG emission mitigations associated with aging dietary patterns.

Distribution of coronal plane alignment of the knee classification in Chinese osteoarthritic and healthy population: a retrospective cross-sectional observational study.

BACKGROUND: Few studies have reported the coronal constitutional alignment of the lower limbs in mainland China. This study aimed to analyse the distribution of the coronal plane alignment of the knee (CPAK) classification in the osteoarthritic (OA) and healthy Chinese populations. MATERIALS AND METHODS: The CPAK distributions of 246 patients (477 knees) with OA and 107 healthy individuals (214 knees) were retrospectively examined using long-leg radiographs. Radiological measurements and CPAK classification of different Kellgren-Lawrence grades in patients with unilateral total knee arthroplasty (TKA) were compared. The clinical outcomes of patients with CPAK type I who underwent mechanical alignment or restricted kinematic alignment during TKA were examined. RESULTS: The most common distributions in the OA and healthy groups were type I and type II, respectively. In patients who underwent unilateral TKA, the most common distribution of knees graded as Kellgren-Lawrence 3-4 was type I. However, the most common distributions of contralateral knees graded as Grade 0-2 were type I and II. For patients with CPAK type I, the mechanical alignment and restricted kinematic alignment groups did not differ significantly concerning postoperative clinical outcomes at 3 months. CONCLUSION: The most common distributions in Chinese osteoarthritic and healthy populations were types I and II, respectively. In addition, OA progression may lead to changes in the CPAK classification.

Immune regulation and inflammation inhibition of Arctium lappa L. polysaccharides by TLR4/NF-κB signaling pathway in cells.

Arctium lappa L. polysaccharides (ALP) are important active ingredients of burdocks with various bioactivities. In the present study, a crude polysaccharide was extracted from A. lappa L. roots and purified using DEAE-52 and Sephacryl™ S-400 columns to reach 99 % purity. This neutral polysaccharide contained fructose, glucose, galactose and arabinose in a ratio of 0.675:0.265:0.023:0.016 and had a Mw of 4256 Da. The immunomodulatory activity and intestinal inflammation inhibitory effects of ALP were investigated in in vitro models, including lipopolysaccharide-induced macrophage RAW264.7 and interleukin (IL)-1ß-induced colon Caco-2 cells. The results revealed that ALP possessed both antioxidant and anti-inflammatory effects by decreasing nuclear factor-E2-related factor 2 mRNA expression and reactive oxygen species. Furthermore, ALP was found to have inhibitory effects on pro-inflammatory cytokines, including IL-8, IL-6, IL-1ß, and tumor necrosis factor-α, as well as inflammatory cytokines, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 by down-regulating the Toll-like receptor 4 (TLR4)/NF-κB (nuclear factor-kappa B signaling) pathway. It indicated that A. lappa L. was an ideal source of bioactive polysaccharides having potential to be developed as functional foods or nutraceuticals to improve immune system and prevent/treat intestinal inflammation.

miR-590-5p/Tiam1-mediated glucose metabolism promotes malignant evolution of pancreatic cancer by regulating SLC2A3 stability.

BACKGROUND: T lymphoma invasion and metastasis 1 (Tiam1) is a tumor related gene that specifically activates Rho-like GTPases Rac1 and plays a critical role in the progression of various malignancies. Glycolysis plays an important role in cancer progression, it is crucial for supplying energy and producing metabolic end products, which can maintain the survival of tumor cells. As yet, however, the mechanism of Tiam1 in glycolysis reprogramming of pancreatic cancer (PC) remains to be clarified. Here, we investigated the functional role of Tiam1 in PC cell proliferation, metastasis and glycolysis reprogramming. It is expected to provide a new direction for clinical treatment. METHODS: The clinical relevance of Tiam1 was evaluated in 66 patients with PC, the effect of Tiam1 on cell proliferation was detected via 5-Ethynyl-2'-deoxyuridine (EdU) and colony formation. The ability of cell migration was detected by the wound healing and Transwell. Quantitative real time polymerase chain reaction (qRT-PCR) and luciferase reporter gene experiments clarify the regulatory relationship of miR-590-5p inhibiting Tiam1. Detection of the molecular mechanism of Tiam1 regulating glucose metabolism reprogramming in PC by glucose metabolism kit. RNA sequencing and Co-Immunoprecipitation (CoIP) have identified glucose transporter protein 3 (SLC2A3) as a key downstream target gene for miR-590-5p/Tiam1. RESULTS: We found that Tiam1 expression increased in PC tissues and was associated with lymph node metastasis. The silencing or exogenous overexpression of Tiam1 significantly altered the proliferation, invasion, and angiogenesis of PC cells through glucose metabolism pathway. In addition, Tiam1 could interact with the crucial SLC2A3 and promote the evolution of PC in a SLC2A3-dependent manner. Moreover, miR-590-5p was found to exacerbate the PC cell proliferation, migration and invasion by targeting Tiam1. Furthermore, the reversing effects on proliferation, migration and invasion were found in PC cells with miR-590-5p/Tiam1 overexpression after applying glucose metabolism inhibition. CONCLUSIONS: Our findings demonstrate the critical role of Tiam1 in PC development and the miR-590-5p/Tiam1/SLC2A3 signaling pathway may serve as a target for new PC therapeutic strategies.

Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein.

Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Thyroid organoids: Advances and applications.

Organoids are derived from stem cells under three-dimensional culture conditions through self-assembly, and they can recapitulate the structural and functional characteristics of organs in vivo during culture. Organoids can be generated from both normal and malignant tissues. Those derived from normal tissues are widely used in the field of regenerative medicine. Meanwhile, tumour-derived organoids retain the phenotypic heterogeneity and atypia of the primary tumour, thereby providing a reliable in vitro model for the study of tumour pathogenesis and treatment. The thyroid gland is one of the most important endocrine organs regulating the body's energy metabolism and growth; however, it is also associated with a high incidence of malignancy. Organoid is an effective tool for thyroid research. Thyroid tumour-derived organoids can inherit the histopathological properties of primary tumours, and thyroid tissue-derived organoids can form follicular structures and secrete thyroid hormones. The above characteristics of organoids provide a reliable way to study the mechanism of thyroid genesis and tumour development in vitro. In this review, we focus on current knowledge and strategies for the establishment of thyroid organoids in thyroid regeneration and tumour research aiming to increase our understanding of the pathogenesis of thyroid tumours and the regenerative treatment of patients with hypothyroidism.

Prevention of Pregabalin-Related Side Effects Using Slow Dose Escalation Before Surgery: A Trial in Primary Total Joint Arthroplasty Within the Enhanced Recovery After Surgery Pathway.

BACKGROUND: The side effects of pregabalin likely occur after the first dose. We aimed to evaluate the effect of 75 milligrams (mg) of pregabalin prescribed as an initial dose with a slow dose escalation for primary total joint arthroplasty within the enhanced recovery after surgery pathway. METHODS: Participants were randomly assigned to two groups. Fifty-eight patients were enrolled, and twenty-nine were assigned to each group. Group 1 (G1) received pregabalin (37.5 mg) twice on the day before surgery, as well as pregabalin 75 mg two hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose of pregabalin at two hours pre-operatively. The primary outcome was dizziness assessed by severity; secondary outcomes included nausea, vomiting, sedation, opioid consumption, independent transfer at six hours post-operatively, time to readiness for independent transfers, time to readiness for discharge, and pain. RESULTS: At two, four, and six hours post-operatively, the proportion of patients experiencing dizziness and nausea was significantly greater in G2 than in G1, and opioid consumption was significantly greater in G2 than in G1 (P = .012). The proportion of independent transfers at six hours post-operatively was significantly greater in G1 than in G2 (P = .010). The time to readiness for independent transfers was significantly shorter in G1 than in G2 (P = .016). CONCLUSION: Prescription of pregabalin 37.5 mg twice on the day before surgery was effective in reducing early postoperative dizziness and nausea after receiving pregabalin 75 mg two hours pre-operatively. It also promoted early independent transfers and reduced opioid consumption.

Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs.

The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.

m6A-Related Angiogenic Genes to Construct Prognostic Signature, Reveal Immune and Oxidative Stress Landscape, and Screen Drugs in Hepatocellular Carcinoma.

Background: m6A modification plays a key role in the development of hepatocellular carcinoma (HCC). Angiogenesis-related genes (ARGs) are increasingly being used to define signatures predicting patient prognosis. The correlations between m6A-related ARGs (mARGs), clinical outcomes, and the immune and oxidative stress landscape are unclear. Methods: Univariate Cox regression analysis of 24 mARGs yielded 13 prognostic genes, which were then analyzed for their enriched functions and pathways. After LASSO regression analysis, a prognostic signature was constructed and its reliability validated. Patients were grouped by risk using the signature score, and then the clinical prognosis, the immune landscape, and the oxidative stress landscape between the two groups were analyzed. Drug sensitivity analysis was performed to identify potentially efficient therapeutic agents. Results: Thirteen prognosis-related mARGs consistently clustered patients with HCC into four groups with significantly different prognosis. Four mARGs (EGF, ITGA5, ITGAV, and PLG) were used to construct a prognostic signature and define risk groups. Among them, EGF, ITGA5, and ITGAV, were defined as prognostic risk factors, while PLG was defined as a prognostic protective factor. Compared to low-risk patients, HCC patients in the high-risk group had a poorer prognosis and showed significant differences in clinical characteristics, enriched pathways, tumor stemness, and tumor microenvironment. The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value. Conclusions: A prognostic model consisting of mARGs can be used to predict the prognosis of HCC patients. The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.

M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma.

Background: M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the "immune landscape", and screen drugs in HCC. Methods: M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene-drug correlation and sensitivity to anti-cancer drugs were conducted. Results: A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Conclusions: Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Exploration of the Tumor Immune Landscape and Identification of Two Novel Immunotherapy-Related Genes for Epstein-Barr virus-associated Gastric Carcinoma via Integrated Bioinformatics Analysis.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a specific molecular subtype of gastric carcinoma with a high proportion of tumor-infiltrating lymphocytes. It is a highly immunogenic tumor that may benefit from immunotherapy. Hence, it is imperative to analyze the immune landscape and identify immunotherapy biomarkers for EBVaGC. In our study, we investigated the immune landscape and identified 10 hub genes for EBVaGC via integrated bioinformatics analysis. We found that EBVaGC expressed more immune-related genes, including common immune checkpoints and human leukocyte antigen (HLA) genes than EBV-negative gastric carcinoma (EBVnGC). The immune score in EBVaGC was higher, which means EBVaGC has greater immune cell infiltration. Ten hub genes (CD4, STAT1, FCGR3A, IL10, C1QA, CXCL9, CXCL10, CXCR6, PD-L1, and CCL18) were detected as candidate biomarkers for EBVaGC. Two hub genes, CXCL9 and CXCR6, were identified as novel immunotherapy-related genes. Taken together, the results of our comprehensive analysis of the immune microenvironment of EBVaGC revealed its unique immune landscape, demonstrating that it is a highly immunogenic tumor. Moreover, we identified hub genes that may serve as potential immunotherapy biomarkers for EBVaGC.

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer.

CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues at both mRNA and protein levels. In the in-house cohort, CDCP1 protein expression was related to several clinicopathological parameters, including age, ER status, PR status, molecular type, and survival status. Kaplan-Meier analysis and Cox regression analysis exhibited that CDCP1 was an important prognostic biomarker in BrCa. In addition, enrichment analysis uncovered that CDCP1 was not only involved in multiple oncogenic pathways, but correlated with overexpression of immune checkpoints. Overall, we reported that increased expression of CDCP1 is a favorable prognostic factor in patients with BrCa. In addition, the correlations between CDCP1 and immune checkpoints provide a novel insight into the adjuvant treatment for immune checkpoint blockade via targeting CDCP1.

The clinicopathological characteristics of early-onset gastric cancer and its evolutionary trends: a retrospective study.

Although gastric cancer (GC) is most common in the elderly population, the rate of early-onset gastric cancer (EOGC) is increasing each year. In this study, the clinicopathological information of 9,406 patients who underwent GC resection in our institution from 2000 to 2019 was collected. We compared the clinicopathological characteristics between the EOGC group, in which patients were younger than 40, and the control group, summarizing the evolutionary trends of the EOGC group's characteristics. Then, we focused on the characteristics of EOGC in different sex groups and the evolutionary trends of female EOGC patients' clinicopathological characteristics. The results showed that a greater proportion of the EOGC group was female (47.32% vs. 23.53%), had poorly differentiated adenocarcinoma (84.78% vs. 64.11%), gastric antrum cancer (59.38% vs. 50.72%) and signet ring cell carcinoma (21.13% vs. 8.51%). Over the past 20 years, the proportion of EOGC patients with T4 stage (10.71% to 41.74%), N3 stage (0 to 30.73%) and poorly differentiated adenocarcinoma (70.37% to 92.23%) has increased. In the female EOGC group, there were more patients with stage III-IV disease (57.23% vs. 43.22%), T4 stage (35.85% vs. 22.60%), and poorly differentiated adenocarcinoma (91.88% vs. 78.68%). Additionally, the proportions of T4 stage (16.13% to 50.50%), N3 stage (0% to 31.68%), and poorly differentiated adenocarcinoma (69.23% to 98.97%) gradually increased. In conclusion, our study not only identified unique clinicopathological characteristics of EOGC but also revealed the evolutionary trends of these indicators, which may provide some theoretical basis for the prevention and diagnosis of EOGC.

Preoperative CECT-based Radiomic Signature for Predicting the Response of Transarterial Chemoembolization (TACE) Therapy in Hepatocellular Carcinoma.

PURPOSE: To evaluate the efficiency of radiomics signatures in predicting the response of transarterial chemoembolization (TACE) therapy based on preoperative contrast-enhanced computed tomography (CECT). MATERIALS: This study consisted of 111 patients with intermediate-stage hepatocellular carcinoma who underwent CECT at both the arterial phase (AP) and venous phase (VP) before and after TACE. According to mRECIST 1.1, patients were divided into an objective-response group (n = 38) and a non-response group (n = 73). Among them, 79 patients were assigned as the training dataset, and the remaining 32 cases were assigned as the test dataset. METHODS: Radiomics features were extracted from CECT images. Two feature ranking methods and three classifiers were used to find the best single-phase radiomics signatures for both AP and VP on the training set. Meanwhile, multi-phase radiomics signatures were built upon integration of images from two CECT phases by decision-level fusion and feature-level fusion. Finally, multivariable logistic regression was used to develop a nomogram by combining radiomics signatures and clinic-radiologic characteristics. The prediction performance was evaluated by AUC on the test dataset. RESULTS: The multi-phase radiomics signature (AUC = 0.883) performed better in predicting TACE therapy response compared to the best single-phase radiomics signature (AUC = 0.861). The nomogram (AUC = 0.913) showed better performance than any radiomics signatures. CONCLUSION: The radiomics signatures and nomogram were developed and validated for predicting responses to TACE therapy, and the radiomics model may play a positive role in identifying patients who may benefit from TACE therapy in clinical practice.

PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation.

Anti-programmed death-1 (PD-1) immunotherapy that aims to restore T cell activity in cancer patients frequently leads to immune-related adverse events such as colitis. However, the underlying mechanism is still elusive. Here, we find that Pdcd1-deficient mice exhibit disrupted gut microbiota and aggravated dextran sulfate sodium (DSS)-induced colitis. In addition to T cells, PD-1 is also substantially expressed in colonic lymphoid tissue inducer (LTi) cells. During DSS-induced colitis, LTi cell activation is accompanied by increased PD-1 expression, whereas PD-1 deficiency results in reduced interleukin-22 (IL-22) production by LTi cells and exacerbated inflammation. Mechanistically, activated LTi cells reprogram their metabolism toward carbohydrate metabolism and fatty acid synthesis, while fatty acid oxidation (FAO) is unchanged. However, PD-1 deficiency leads to significantly elevated FAO in LTi cells, which in turn attenuates their activation and IL-22 production. Consistently, FAO suppression efficiently restores IL-22 production in Pdcd1-/- LTi cells. Thus, our study provides unforeseen mechanistic insight into colitis occurrence during anti-PD-1 immunotherapy through LTi cell metabolic reconfiguration.