Background Advanced gastric cancer (aGC) exhibits substantial heterogeneity in response to combination immunotherapy. Circulating cell-free DNA (cfDNA) enables non-invasive profiling of tumor dynamics and may provide biomarkers for response prediction. Methods We enrolled 94 patients with aGC undergoing combination immunotherapy and assigned them to a discovery set (n=49) and an internal validation set (n=45). Plasma cfDNA was collected pre-treatment and post-treatment and profiled by low-pass whole-genome sequencing and whole-genome bisulfite sequencing in the discovery set, with targeted bisulfite sequencing used in the validation set. Results The discovery set included 34 responders and 15 non-responders, and the validation set included 30 responders and 15 non-responders. We found that responders showed longer cfDNA, lower cfDNA tumor fraction (median: 0.06 vs 0.01, p<0.001), reduced chromosomal instability (median genomic instability index: 0.026 vs 0.007, p<0.001), and higher global methylation (median: 0.715 vs 0.724, p=0.007). Additionally, the differentially methylated region (DMR) at chr20:25849353-25849490 consistently showed higher methylation in responders in both the discovery (adjusted p=0.006) and validation sets (adjusted p=0.049). A predictor based on this DMR outperformed programmed death-ligand 1 (PD-L1) combined positive score (CPS) with area under the curve (AUCs) of 0.79 (discovery: 95% CI 0.65 to 0.93) and 0.72 (validation: 95% CI 0.54 to 0.91). When integrating PD-L1 CPS with this DMR, the AUCs were 0.81 (discovery: 95% CI 0.67 to 0.95) and 0.75 (validation: 95% CI 0.56 to 0.94), respectively. For on-treatment monitoring, three DMRs increased specifically in responders; among them, increased methylation of chr8:110479193-110480324 and chr8:50891437-50892120 was associated with improved progression-free survival (median: 4.90 vs 11.57 months, p<0.001; median: 5.20 vs 10.20 months, p=0.007). Conclusion Integrated cfDNA profiling captures immunotherapy-associated molecular dynamics in aGC. A single pretreatment cfDNA methylation marker (chr20:25849353-25849490) improves response prediction beyond PD-L1 CPS and represents a potential predictive biomarker for combination immunotherapy.

The molecular mechanisms of colorectal cancer (CRC)–ovarian metastasis (OM) remain unclear, and this study aimed to identify the genetic determinants. We retrospectively included 81 CRC patients developing OM. Treatment-naïve primary and metastatic lesion tissue samples underwent DNA sequencing to identify gene-level and global genomic OM determinants. Two external CRC cohorts (MSKCC cohort, N = 643; TCGA cohort, N = 448) were analyzed for mechanism exploration. Copy number variations (CNVs) of SMAD4 (p < 0.01) and SMAD2 (p < 0.01) were more common in metastatic lesions than in primary lesions, with similar findings (SMAD4, p = 0.05; SMAD4, p = 0.02) in 28 pairs of matched samples. Unfavorable overall survival was associated with SMAD4 (p < 0.001) and SMAD2 (p = 0.09) CNV loss. RNA sequencing data demonstrated an upregulated angiogenesis pathway related to SMAD4 (q = 0.03) and SMAD2 (q < 0.001) CNV loss. Metastatic lesions exhibited higher chromosome instability scores than primary lesions (p < 0.01), consistent with findings in the MSKCC cohort (p < 0.001). Compared to metachronous metastasis, the primary (p = 0.04) and metastatic (p = 0.01) lesions of synchronous metastasis showed a heavier APOBEC signature burden. FLT1 (17.6

Immunotherapy benefits many solid tumors, yet efficacy in pancreatic cancer (PC) remains limited given its immunologically cold phenotype. We evaluated the real-world effectiveness, safety, and treatment patterns of serplulimab-based regimens in unresectable locally advanced or metastatic PC. This two-center observational study retrospectively included adults with pathologically confirmed advanced PC who received serplulimab-based therapy as first- or later-line treatment. Short-term efficacy was assessed per RECIST v1.1, safety per CTCAE v5.0, and long-term benefit by overall survival (OS). Among the 42 included patients, 24 received first-line (1 L) therapy and 18 received second-line or later (≥ 2 L) therapy. At a median follow-up of 17.7 months, the objective response rate (ORR) in the 1 L group was 25.0

OBJECTIVE:The relationship among body mass index (BMI), Charlson comorbidity index (CCI), and depression forms a complex interplay that affects both physical and mental health. However, whether CCI mediates the association between BMI and depression remains unclear. In this study, we aimed to elucidate the mediating role of CCI in the relationship between BMI and depression. METHODS:This study used data from the National Health and Nutrition Examination Survey, a program of the National Center for Health Statistics in the United States, including 23,639 participants from 2007 to 2020. Wilcoxon rank-sum and Rao-Scott adjusted chi-square tests were employed to compare characteristics between adults with and without depression. Weighted logistic regression and restricted cubic spline models were applied to investigate the pairwise associations among BMI, CCI, and depression. Mediation analysis was performed to assess whether CCI mediated the relationship between BMI and depression. RESULTS:Of the 23,639 participants, 2128 (9.0 %) had depression. Significant associations were observed between BMI and CCI; CCI and depression; and BMI and depression (P < 0.001). A U-shaped relationship between BMI and depression odds was identified, with the lowest odds at a BMI of 23 kg/m2. Mediation analysis revealed that CCI partially mediated the BMI-depression relationship, accounting for 19.5 % of the total effect. CONCLUSIONS:The results suggest that CCI plays a mediating role in the association between BMI and depression, and that improved chronic disease management may be associated with lower odds of depression in high BMI populations.

OBJECTIVE:Colorectal cancer (CRC) is the third most prevalent malignant tumor type and the second leading cause of cancer-related death. Sequence similarity family 50 member A (FAM50A) plays a vital role in numerous disease processes, including tumor progression. This study aimed to evaluate the prognostic significance of FAM50A in CRC and to explore its role in CRC cell proliferation. METHODS:TCGA and GTEX databases and immunohistochemical staining (IHC) was used to study the expression of FAM50A in CRC tissues. Patient survival data were used to assess the prognostic significance of FAM50A in CRC using Kaplan-Meier analysis and Cox regression analysis. The Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony-formation assays were employed to assess the impact of FAM50A on tumor cell proliferation. Flow cytometry was used to detect the changes of cell cycle. The cell cycle and cycle-related proteins were measured via western blotting (WB) to explore the potential mechanisms involving in cancer progresses. RESULTS:The results of IHC revealed a notable upregulation of FAM50A expression levels in CRC tissue compared with adjacent normal tissue. Moreover, FAM50A expression was positively correlated with N and TNM stages in 145 patients with CRC. Cox regression analysis and construction of a nomogram revealed that high FAM50A expression was a prognostic indicator for poor overall survival in patients with CRC. Knockdown of FAM50A decreased cell proliferation ability, the proportion of EdU positive cells, and the number of CRC cell colonies, whereas overexpressing FAM50A promoted proliferative phenotypes. Knocking down FAM50A induced a significant increase in the number of cells in the S phase. Meanwhile, CyclinA2 and CDK2 were significantly reduced after FAM50A knocking down. CONCLUSION:FAM50A may be a novel prognostic marker for CRC, and may participate in regulating tumor progression by targeting the CyclinA2/CDK2 signal pathway.

e14609 Background: Serplulimab has demonstrated promising efficacy as a first-line treatment for esophageal squamous cell carcinoma (ESCC) with a combined positive score (CPS) ≥1 in clinical trials. However, real-world evidence regarding its effectiveness and safety in advanced esophageal cancer remains limited. This study aimed to evaluate the real-world outcomes of serplulimab-based therapy in patients with metastatic or locally advanced esophageal carcinoma (EC). Methods: This multicenter, retrospective study included patients diagnosed with metastatic or unresectable locally advanced EC who received first-line serplulimab-containing therapy between March 2022 and December 2023. Data were collected from medical records, including patient demographics, disease characteristics, treatment regimens, therapeutic response, and adverse events (AEs). Key endpoints included objective response rate (ORR), disease control rate (DCR), real-world progression-free survival (rwPFS), real-world overall survival (rwOS), and safety outcomes. Results: A total of 104 patients were included, with a mean age of 68 years (81 [77.9%] male). Histological subtypes comprised ESCC (80.8%), combined small cell and adenocarcinoma (9.6%), mixed neuroendocrine–non-neuroendocrine neoplasms (5.8%), and neuroendocrine neoplasm (3.8%). Of these, 97 patients (93.3%) received concurrent chemotherapy, 10 (9.6%) underwent targeted therapy, and 21 (20.2%) received radiotherapy. Among 90 evaluable patients, the ORR was 40.0% (95% CI: 29.8–50.9), while the DCR was 97.8% (95% CI: 92.2–99.7). After a median follow-up of 6.8 months (range: 0.6–25.4), the median rwPFS was 12.0 months (95% CI: 8.9–NE), and the median rwOS was not reached (95% CI: 13.3–NE). The estimated 12-month survival rate was 73.5% (95% CI: 60.4–89.3). Subgroup analysis revealed a significantly longer median PFS in patients aged ≥65 compared to those < 65 years (12.0 vs. 6.9 months, P = 0.022). Overall, 55.8% of patients (n = 58) experienced AEs, 18.3% (n = 19) reported treatment-related adverse events (TRAEs), and 1.9% (n = 2) experienced serious adverse events (SAEs), including hyperkalemia and leukopenia. Conclusions: This real-world study supports the efficacy of serplulimab as a first-line treatment for metastatic or locally advanced EC, encompassing a wide range of histological subtypes and diverse patient populations. The observed outcomes align with those from randomized controlled trials. The safety profile was consistent with previous findings, with no new safety concerns identified.

Immunotherapy has brought clinical benefits for patients with advanced or late-stage gastric cancer. This real-world study aimed to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with locally advanced gastric cancer (LAGC). Patients with LAGC (cT2-4bN1-3M0) were enrolled in this retrospective study. Patients received either neoadjuvant immunochemotherapy or chemotherapy alone before surgery. The primary endpoint was the pathological complete response (pCR) rate. A total of 111 patients were included in this study, with 49 received neoadjuvant PD-1 inhibitors combined with chemotherapy (Group A) and 62 received chemotherapy alone (Group B). pCR rate of Group A was significantly higher than that of Group B (22.4

Programmed death-1 (PD-1) inhibitors combined with chemotherapy have become a standard treatment for human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (GC). However, responses vary, and effective prognostic biomarkers are needed. This study aimed to investigate the prognostic value of dynamic changes in carcinoembryonic antigen (CEA) levels in this patient population. This retrospective cohort study included 96 patients with HER2-negative metastatic or locally advanced GC treated at our institution between June 2021 and June 2024. All patients received PD-1 inhibitors plus chemotherapy. Serial CEA measurements were used to construct a linear model (Y = ax + b) for each patient, where ‘a’ represents the slope of CEA change. Using a receiver operating characteristic (ROC) curve analysis for predicting 6-month progression-free survival (PFS), an optimal cutoff slope of a = 0.85 was determined. Patients were stratified into a Slow-riser group (a ≤ 0.85, n = 70) and a Rapid-riser group (a > 0.85, n = 26). We compared treatment efficacy, survival outcomes, and adverse events between the groups. Prognostic factors for PFS were identified using univariate and multivariate Cox proportional hazards models, in line with TRIPOD principles. During treatment, serial CEA levels exhibited a fluctuating pattern with an overall upward trend. Compared to the Rapid-riser group, the Slow-riser group had a significantly higher disease control rate (DCR) (71.4

Angiogenesis is crucial for minimising ischemic injury postmyocardial infarction (MI), making it a significant target for cardioprotective therapies. While Kindlin-3 has been linked to angiogenesis in breast cancer, its specific function in the context of MI remains largely unexplored. Although Kindlin-3 has been implicated in breast cancer-related angiogenesis, its role in MI remains underexplored. This study investigates the role of Kindlin-3 in promoting angiogenesis, a process critical for cardiac recovery following MI. The study demonstrated a significant upregulation of Kindlin-3 in cardiac microvascular endothelial cells (CMECs) in mice post-MI. Overexpression of Kindlin-3, achieved through cardiotropic adeno-associated virus serotype 9 (AAV9) with the endothelial-specific promoter Tie2, enhanced myocardial angiogenesis, improved cardiac function, decreased cardiomyocyte apoptosis and reduced fibrosis. In vitro, Kindlin-3 overexpression promoted CMECs proliferation, migration, tube formation and the expression of angiogenesis-related genes. Conversely, Kindlin-3 knockdown exerted opposite effects. Mechanistically, Kindlin-3 activated the Notch signalling pathway, as its effects were abrogated by the Notch inhibitor DAPT and β1 integrin knockdown. This study identifies Kindlin-3 as a novel enhancer of angiogenesis and suggests its potential as a therapeutic target for myocardial repair.

Background:Immune checkpoint inhibitors (ICIs) have shown significant clinical benefits in the treatment of advanced human epidermal growth factor receptor 2 (HER2) negative gastric cancer, and are now widely used in combination with chemotherapy for first-line treatment. However, significant individual variability in the treatment response poses challenges in optimizing therapeutic strategies. Systemic inflammatory biomarkers are gaining attention for their ability to reflect tumor-related inflammation and the immune response balance. These markers could be used to predict treatment outcomes and guide personalized therapy. This study aimed to evaluate the prognostic value of peripheral blood inflammatory markers, such as the Systemic Immune Inflammation Index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR), in patients with HER2 negative advanced gastric cancer undergoing first-line immunotherapy with ICIs. Methods:The clinical data of advanced gastric cancer patients treated with immunotherapy at Jiangsu Cancer Hospital between January 2018 and December 2023 were retrospectively collected. The patients were categorized into progressive disease (PD) and effective treatment [complete response (CR), partial response (PR), stable disease (SD)] groups based on their response after two cycles of treatment. The changes in the SII, NLR, PLR, and CAR based on the baseline data and post-treatment measurements were evaluated. The optimal cut-off values for these markers were determined using X-tile software based on their distribution characteristics. Kaplan-Meier survival analysis, log-rank tests, and Cox regression models were used to assess the prognostic ability of these markers. Results:A total of 142 patients with advanced gastric cancer were included in the study, of whom, 22 had PD after first-line immunotherapy, and 120 had SD. No significant differences were observed in the baseline characteristics of the patients between the effective treatment group and the PD group (P>0.05). Using X-tile software, the optimal cut-off values for the SII, NLR, PLR, and CAR were 548.22 [hazard ratio (HR): 2.421; 95% confidence interval (CI): 1.214-3.710], 3.75 (HR: 3.210; 95% CI: 2.030-5.115), 245.65 (HR: 2.137; 95% CI: 1.577-4.240), and 0.56 (HR: 1.846; 95% CI: 1.388-2.245), respectively. After two cycles of immunotherapy, the NLR, PLR, SII, and CAR values of the patients in the effective treatment (CR + PR + SD) group all decreased significantly. The Kaplan-Meier survival curve analysis showed that the patients with high SII, NLR, PLR, and CAR values had a poorer prognosis in terms of progression-free survival (PFS) and overall survival (OS) (P<0.05) than those with low values. Conclusions:Inflammatory markers (i.e., the SII, NLR, PLR, and CAR) can be used to predict the prognosis of HER2 negative advanced gastric cancer patients undergoing first-line immunotherapy.

BACKGROUND:Microsatellite stability influences the prognosis of patients with colorectal cancer (CRC). However, there are few studies on the relationship between microsatellite stability and lymph node metastasis (LNM) in CRC. OBJECTIVE:This study aims to elucidate the relationship between microsatellite stability and LNM in CRC and to investigate potential underlying mechanisms. METHODS:A retrospective analysis was performed on a cohort of 309 CRC patients, who were categorized into microsatellite instability (MSI) and microsatellite stability (MSS) groups based on their microsatellite status. Clinical and pathological indicators were collected, and differences between the two groups were assessed. The tertiary lymphoid structures (TLS) in both groups were examined using immunohistochemistry and immunofluorescence to compare differences in density, maturity, and the ratio of CD8+T cells. Establishing the relationship between microsatellite stability, TLS characteristics, and lymph node metastasis. RESULTS:The TNM staging for patients in the MSI group was significantly earlier compared to those in the MSS group. Subsequent analysis of pathological indicators demonstrated that the MSI group exhibited a significantly lower incidence of lymph node metastases (31.4% vs. 47%, P=0.005), while no statistically significant differences were observed in other pathological indicators (P>0.05). Examination of CRC tissue sections revealed that the MSI group possessed a greater number and maturity of tertiary lymphoid structures, as well as a higher proportion of CD8+T cells. CONCLUSION:MSI may decrease the incidence of LNM in CRC, potentially as a result of the activation of local anti-tumor immune responses facilitated by MSI.

Approximately 5% of female patients with colorectal cancer (CRC) develop ovarian metastasis (OM), predominantly in young women and leading to poorer survival. As the molecular mechanisms underlying OM remain unclear, this study aimed to identify the genetic determinants of OM and to investigate the mechanisms of synchronous and metachronous metastasis. We retrospectively enrolled 81 patients with CRC who had developed OM (28 with matched primary and metastatic lesion samples, 30 with primary lesion, 23 with metastatic samples). Treatment-naïve primary and metastatic lesion tissue samples underwent next-generation sequencing targeting 437 genes to identify gene-level and global genomic determinants of OM. Two external CRC cohorts (MSKCC cohort, N=643; TCGA cohort, N=448) were analyzed for further mechanism exploration. Among 81 included patients, copy number variations (CNVs) of SMAD4 (p<0.01) and SMAD2 (p<0.01) were more frequently detected in metastatic lesions than primary lesions, with similar findings in 28 pairs of matched samples (SMAD4, p=0.05; SMAD4, p=0.02). Associations of SMAD4 (p<0.001) and SMAD2 (p=0.09) CNV loss with unfavorable overall survival were observed in the MSKCC cohort. RNA sequencing data from the TCGA cohort demonstrated up-regulated angiogenesis pathway related to SMAD4 (q=0.03) and SMAD2 (q<0.001) CNV loss. Higher chromosome instability was observed in metastatic lesions than primary lesions in the study cohort (p<0.01; matched samples, p=0.08), consistent with the findings in the MSKCC cohort (p<0.001). The APOBEC mutational signature was related to OM synchronous metastasis, with heavier burdens in both the primary (p=0.04) and metastatic (p=0.01) lesions of synchronous metastasis than those of metachronous metastasis; however, primary lesions of metachronous metastasis exhibited higher whole-genome doubling fraction (p=0.04) and ploidy (p=0.02). Moreover, in metastatic lesions, FLT1 (17.6%, p=0.05) and ZNF217 (17.6%, p=0.05) CNV gains were exclusively detected of synchronous metastasis when compared to metastatic lesions of metachronous metastasis. SMAD4/2 CNV loss and chromosome instability may drive OM in CRC. Synchronous metastasis displays distinct gene-level and global genome features different from metachronous metastasis. Ying Fang, Yan Sun, Xiaotian Zhao, Xiaoying Wu, Jiaohui Pang, Haimeng Tang, Qiuxiang Ou, Che Chen, Ziwei Xu. Gene-level and global genomic insights into colorectal cancer ovarian metastasis: Molecular mechanisms and determinants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3398.

Lung adenocarcinoma is a globally prevalent malignant tumor with a high death rate, notorious for its invasive and metastatic capabilities. SGO2 is a key protein in the cell division process, influencing the development of various malignant tumors. However, research on the biological functions of SGO2 in Lung adenocarcinoma remains limited. By utilizing the Cancer Genome Atlas (TCGA) database, we performed an analysis of SGO2 expression levels in a cohort comprising 206 Lung adenocarcinoma patients in comparison to 200 non-neoplastic control specimens. Subsequently, we validated our findings through immunohistochemical staining in a subset of 21 Lung adenocarcinoma cases from Nanjing Second Hospital. Furthermore, the functional role of SGO2 in the H1299 cell line was assessed through a series of experiments including Western blotting, CCK-8 assays, Transwell assays for invasion, wound healing assays, and flow cytometric analysis. The study also explored the influence of SGO2 on the regulation of MAD2 expression. The enhancement of SGO2 expression in Lung adenocarcinoma tissues was significantly associated with a poor prognosis in patients. A reduction in SGO2 expression markedly decreased the proliferative, migratory, and invasive capabilities of H1299 cells, a phenomenon that may be attributed to the regulation of MAD2 expression by SGO2. SGO2 exerted a pivotal influence on the metastatic behavior of Lung adenocarcinoma cells by governing the expression of MAD2, thereby contributing substantially to the molecular pathogenesis of Lung adenocarcinoma.

Advanced ScienceVolume 11, Issue 23 2470136 Inside Back CoverOpen Access EZH2 Inhibition Enhances PD-L1 Protein Stability Through USP22-Mediated Deubiquitination in Colorectal Cancer (Adv. Sci. 23/2024) Jiaqi Huang, Jiaqi HuangSearch for more papers by this authorQianqian Yin, Qianqian YinSearch for more papers by this authorYuqing Wang, Yuqing WangSearch for more papers by this authorXin Zhou, Xin ZhouSearch for more papers by this authorYunyun Guo, Yunyun GuoSearch for more papers by this authorYuanjun Tang, Yuanjun TangSearch for more papers by this authorRui Cheng, Rui ChengSearch for more papers by this authorXiaotong Yu, Xiaotong YuSearch for more papers by this authorJie Zhang, Jie ZhangSearch for more papers by this authorChen Huang, Chen HuangSearch for more papers by this authorZhanya Huang, Zhanya HuangSearch for more papers by this authorJianlin Zhang, Jianlin ZhangSearch for more papers by this authorZhengyang Guo, Zhengyang GuoSearch for more papers by this authorXiao Huo, Xiao HuoSearch for more papers by this authorYan Sun, Yan SunSearch for more papers by this authorYanfang Li, Yanfang LiSearch for more papers by this authorHao Wang, Hao WangSearch for more papers by this authorJianling Yang, Jianling YangSearch for more papers by this authorLixiang Xue, Lixiang XueSearch for more papers by this author Jiaqi Huang, Jiaqi HuangSearch for more papers by this authorQianqian Yin, Qianqian YinSearch for more papers by this authorYuqing Wang, Yuqing WangSearch for more papers by this authorXin Zhou, Xin ZhouSearch for more papers by this authorYunyun Guo, Yunyun GuoSearch for more papers by this authorYuanjun Tang, Yuanjun TangSearch for more papers by this authorRui Cheng, Rui ChengSearch for more papers by this authorXiaotong Yu, Xiaotong YuSearch for more papers by this authorJie Zhang, Jie ZhangSearch for more papers by this authorChen Huang, Chen HuangSearch for more papers by this authorZhanya Huang, Zhanya HuangSearch for more papers by this authorJianlin Zhang, Jianlin ZhangSearch for more papers by this authorZhengyang Guo, Zhengyang GuoSearch for more papers by this authorXiao Huo, Xiao HuoSearch for more papers by this authorYan Sun, Yan SunSearch for more papers by this authorYanfang Li, Yanfang LiSearch for more papers by this authorHao Wang, Hao WangSearch for more papers by this authorJianling Yang, Jianling YangSearch for more papers by this authorLixiang Xue, Lixiang XueSearch for more papers by this author First published: 19 June 2024 https://doi.org/10.1002/advs.202470136AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Colon Cancer EZH2 inhibitor can activate the expression of deubiquitinase USP22 in colorectal cancer via canonical epigenetic regulation, thereby stabilizing PD-L1 protein and enhancing its expression, resulting in immune evasion and compromised anti-tumor efficacy. Combination with immunotherapy can overcome the immune suppressive effects of EZH2 inhibitors and achieve better outcome. More details can be found in article number 2308045 by Hao Wang, Jianling Yang, Lixiang Xue, and co-workers. Volume11, Issue23June 19, 20242470136 RelatedInformation

BackgroundMigraine is a widespread, recurrent primary headache disorder primarily characterized by severe pulsatile headache, typically on one or both sides. It is often accompanied by nausea, vomiting, and hypersensitivity to sound and light. Despite the availability of multiple drugs for migraine management, the condition often becomes chronic due to untimely or irrational drug use, significantly distressing patients and increasing the burden on families and society. Over the past two decades, numerous clinical studies on migraine have been published. This study aimed to provide a comprehensive summary of the current status and trends of migraine clinical trials through bibliometric analysis.MethodsWe used visual network tools such as CiteSpace and VOSviewer to perform a knowledge graph analysis of publications related to migraine clinical trials extracted from the WoSCC.ResultsThis study analyzed 1,129 articles published in 389 journals from 61 countries. The number of publications on migraine clinical trials has steadily increased from 2004 to 2023. The United States and Albert Einstein College of Medicine are the leading countries and institutions in this field, respectively. Richard B. Lipton is the most prolific author, making significant contributions to the research. The journal Headache has the highest number of publications and citations in this area. Keywords such as “efficacy,” “RCT,” “CGRP,” “prophylaxis,” “disability,” “depression,” “questionnaire,” and “real-world effectiveness” received significant attention.ConclusionThis study identified reliable research hotspots and provided directions for clinicians. The treatment of migraine continues to be challenging. Future trends may include continued growth in migraine classification, risk factor analysis, and comorbidity studies. Research on CGRP and epigenetics will advance the progress of precision medicine in the migraine field.

Association between Plasma Tocopherols and Lung Cancer Risk by Use of Dietary Supplements

Background:Postoperative delirium (POD) is a common complication in operative patients. Neuroinflammation has been reported to be a potential mechanism associated with the development of POD. Identifying available inflammatory markers such as C-reactive protein (CRP) would aid clinicians in early detection of POD. Previous studies have demonstrated that CRP may be a promising predictive marker for POD. Thus, this study aimed to explore the association between CRP and POD among those elderly colorectal cancer (CRC) patients.Methods:643 patients with CRC were included in this study. CRP levels were measured before operation and on postoperative day 1. The univariate and multivariate regression analyses were used to identify risk factors for POD.Results:Of 643 patients with CRC, 112 cases (17.4%) had POD. CRC patients with POD showed older age, higher CRP level on postoperative day 1, and higher percentage of smoking, diabetes mellitus, and chronic obstructive pulmonary disease (COPD) than CRC patients without POD. Preoperative CRP level was not associated with the POD. Univariate and multivariate regression analyses showed that older age (> 70 years), diabetes mellitus, COPD, and higher CRP level on postoperative day 1 (> 48 mg/L) were risk factors for POD in CRC patients.Conclusion:Postoperative CRP level is an independent indicator for POD among CRC patients, suggesting the predictive role of postoperative CRP levels for POD in elderly CRC patients undergoing surgery.

Abstract Objective: This study aims to investigate the potential enhancement of diagnostic accuracy in gastric cancer through the combined detection of serum tumor markers (CST4, CEA, CA72-4, CA125, CA19-9). Additionally, we examine CST4 levels in both preoperative and postoperative gastric cancer patients to evaluate the correlation between CST4 levels and tumor burden. Results: In gastric cancer, the positive rates of CST4, CEA, CA72-4, CA125, and CA19-9 were notably higher (20.34%, 20.76%, 14.41%, 8.9%, 11.44%, respectively) compared to those in the control group (4.35%, 4.35%, 0%, 1.45%, 7.25%, respectively). The sensitivity of these markers were as follows: CST4 (0.20), CEA (0.21), CA72-4 (0.25), CA125 (0.09), and CA19-9 (0.11). Their respective specificities were 0.96, 0.96, 1.0, 0.99, and 0.93. When these five tumor markers were combined, the AUC area increased to 0.74, indicating that the combined use of these markers significantly improved diagnostic efficacy compared to individual tests. Furthermore, significant differences were observed in CST4 levels pre- and post-operation in gastric cancer patients with varying stages, tumor sizes, and lymph node metastases. Notably, a significant difference in CST4 levels was found before and after surgery in patients with poorly differentiated gastric cancer (P < 0.001), but no such difference was observed in well-differentiated gastric cancer (P = 0.438). Conclusion: CST4, CEA, CA72-4, CA125, and CA19-9 all hold significant value in the diagnosis of gastric cancer. Specifically, serum CST4 may serve as a suitable tumor marker for gastric cancer screening. The combined use of CST4, CEA, CA72-4, CA125, and CA19-9 can significantly enhance the diagnostic accuracy for gastric cancer. Importantly, postoperative CST4 levels in gastric cancer patients were significantly lower than preoperative levels, with the exception of patients with well-differentiated tumors.

Cardiovascular diseases (CVD) are main public health concerns highly prevalent in industrialized societies where human health is threatened by a series of environmental pollutants, particularly heavy metal contaminants. We aimed to find out if blood heavy metals are associated with the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in a nationally representative sample of US adults. We analyzed the cross-sectional data on blood heavy metals of 3268 non-Hispanic white participants aged 40–79 years from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. We introduced a risk estimation algorithm, namely the 2013 Pooled Cohort Equations (PCE), to assess the risk for ASCVD over a 10-year period. The 10-year risk for ASCVD was categorized as either reduced risk (< 7.5

Objectives. This study aims at investigating the differences of clinicopathological features and postoperative prognosis in three different types of neuroendocrine differentiation-related gastric cancers. Methods. From January 1, 2015 to September 30, 2016, 47 patients diagnosed with neuroendocrine differentiation-related gastric cancers were collected from 1095 patients with gastric cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery, Jiangsu Cancer Hospital. Patients were followed up regularly, and the last follow-up time was October 25, 2021. A total of 38 cases met the inclusion criteria and completed follow-up. The clinicopathological characters and immunohistochemical results of these three special pathological types of gastric cancer (adenocarcinoma with neuroendocrine differentiation, mixed adenoneuroendocrine carcinoma, and neuroendocrine carcinoma of the stomach) patients were compared. Tissues from these patients were tested with immunohistochemical markers synaptophysin (Syn), chromogranin A (CgA), and Ki-67. The Kaplan–Meier method and log-rank test were used to analyze the effect of different histological types of gastric cancer on overall survival (OS). The differences in positive rates of chromogranin A (CgA) and Ki-67 were analyzed by univariate Cox regression analysis as independent risk factors that may affect the survival of gastric cancer patients. Results. Ki-67 and N staging were significantly correlated with OS in gastric cancer patients and were independent prognostic factors affecting the survival of gastric cancer patients. There was no statistical difference in OS between the two histopathological types (adenocarcinoma with neuroendocrine differentiation and mixed adenoneuroendocrine carcinoma) of gastric cancer patients. There were no significant differences in the positive rates of immunohistochemical markers Syn, CgA, and Ki-67 in gastric cancer patients with different histological types. Conclusion. The combined detection of Syn and CgA is of great value for the diagnosis of neuroendocrine differentiation-related gastric cancers, Ki-67 is of significance for the prognosis prediction of neuroendocrine differentiation-related gastric cancers, regional lymph node metastasis has a great impact on tumor prognosis, and the N staging determines the necessity of postoperative adjuvant chemotherapy for patients with neuroendocrine differentiation-related gastric cancer.