Clinical and Experimental Medicine最新文献

{"title":"The reciprocal regulation between autophagy and IL-22: implications for immunity and therapy.","authors":"Yang Yu, Mingbiao Qiao, Jinbo Liu, Yuanbiao Guo, Yueshan Sun","doi":"10.1007/s10238-025-01695-y","DOIUrl":"https://doi.org/10.1007/s10238-025-01695-y","url":null,"abstract":"<p><p>Autophagy, a critical cellular process for maintaining homeostasis, involves the degradation and recycling of cellular components through double-membraned vesicles that are transported to lysosomes. This mechanism plays a pivotal role in the immune system by influencing cell fate decisions and functional differentiation. Emerging evidence indicates that autophagy significantly impacts the differentiation and function of T cells and group 3 innate lymphoid cell (ILC3), which are the primary producers of Interleukin-22 (IL-22). IL-22, a key cytokine involved in modulating immune responses and maintaining tissue integrity, is particularly important in combating inflammatory diseases, infections, and cancer. It exerts its effects through a signaling pathway that involves the IL-22R1 and IL-10R2 receptors. Studies have demonstrated that IL-22 can promote autophagy by activating the AMPK pathway and that its intervention can upregulate the expression of autophagy-related genes, underscoring its significant role in the regulation of autophagy. These findings reveal a complex relationship and bidirectional relationship between autophagy and IL-22, highlighting their multifaceted interactions under both physiological and pathological conditions. This review aims to provide a detailed exploration of the dynamic interplay between autophagy and IL-22, with a focus on their mutual regulatory mechanisms, functional significance, and potential for therapeutic interventions. By performing a comprehensive analysis, we sought to clarify the intricate cross talk between autophagy and IL-22, thereby advancing our understanding of their roles in cellular and immune homeostasis and their potential as targets for clinical interventions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"187"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized drug stratification using endoscopic samples to assess ex vivo gastric cancer tissue susceptibility to chemotherapy and immune checkpoint inhibitors.","authors":"Laura Hennig, Astrid Monecke, Ngoc Anh Hoang, René Thieme, Sebastian Prill, Albrecht Hoffmeister, Jan Tuennemann, Ingo Bechmann, Florian Lordick, Sonja Kallendrusch","doi":"10.1007/s10238-025-01694-z","DOIUrl":"https://doi.org/10.1007/s10238-025-01694-z","url":null,"abstract":"<p><p>Customizing drug treatments based on individual tumor susceptibility and patient-specific factors is a complex task, highlighting the need for better predictive models tailored to each patient. Preserving tumor architecture is one strategy to address the intricate interactions between stromal cells and tumor cell populations within a patient. In this study, we explored the feasibility of using pretherapeutic endoscopic tissue cultures from patients (ePDTCs) with gastric and esophagogastric junction cancers to assess individual drug susceptibility. We treated these endoscopic tissue slice cultures with 5-FU (1 µM), a modified FLOT regimen comprising 5-FU (10 µM), leucovorin (10 µM), oxaliplatin (20 µM), and docetaxel (0.1 µM), the active metabolite of irinotecan (SN38, at 1 µM and 10 µM) and the PD-1 inhibitor nivolumab (3 µg/ml). Analysis of the tumor tissue revealed stable adaptations to the culture environment, which were further enhanced by adding 2% autologous human serum to the culture media. Dose-dependent responses were observed with SN38 across all samples and individual susceptibility at low concentrations. Both 5-FU and the FLOT regimen as well as PD-1 inhibition, tested at bioavailable dosages, further demonstrated individualized responses in ePDTCs. This study shows that ePDTCs can effectively assess tissue susceptibility to drugs, warranting further investigation in larger cohorts to validate this model's potential alongside clinical treatments.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"188"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a prediction model for cholangitis after percutaneous transhepatic cholangioscopic lithotripsy.","authors":"Lve Cheng, Junke Li, Qujin Li, Xiong Ding, Jie Liu, Mengjia Shi, Shijia Huang, Junwei Niu, Shengwei Li, Yao Cheng","doi":"10.1007/s10238-025-01719-7","DOIUrl":"10.1007/s10238-025-01719-7","url":null,"abstract":"<p><p>Cholangitis is a common complication of percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) for hepatolithiasis, but risk assessment tools are lacking. This study aimed to identify predictors of cholangitis after PTCSL and develop a predictive nomogram. This retrospective study analysed 245 patients who underwent 450 PTCSL sessions between 1 January 2016 and 1 January 2024. All sessions demonstrating cholangitis complications were classified into the cholangitis group, while the remaining sessions were classified into the non-cholangitis group. All the sessions were divided into training and validation sets. Least absolute shrinkage and selection operator (LASSO) analysis was conducted to preliminarily select predictors of cholangitis complications. Multivariable logistic regression was performed to identify factors for constructing the nomogram. Cholangitis was diagnosed in 51 patients (62 sessions), for an incidence of 13.78% (62 among 450 sessions). Three characteristic variables were included in the model: operation technique (odds ratio [OR] = 0.235, 95% confidence interval [CI]: 0.105-0.524, p < 0.001), globulin (OR = 1.077, 95%CI:1.026-1.131, p = 0.003), and postoperative prophylactic dexamethasone (OR = 0.286, 95%CI:0.145-0.564, p < 0.001). The area under the curve (AUC) for the nomogram was 0.749 (95% CI, 0.673-0.826) in the training set and 0.721 (95% CI, 0.593-0.849) in the validation set, demonstrating relatively high discriminability. The calibration curves demonstrated the consistency between the predicted and actual values. Decision curve analysis indicated that the nomogram offers net clinical benefits. Operation technique, globulin, and postoperative prophylactic dexamethasone may predict cholangitis after PTCSL. We developed a nomogram to estimate the risk of post-PTCSL cholangitis, which demonstrated good predictive performance.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"185"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamer-based approaches in leukemia: a paradigm shift in targeted therapy.","authors":"Alireza Bayani, Munthar Kadhim Abosaoda, Jasur Rizaev, Mobina Nazari, Zahra Jafari, Hamed Soleimani Samarkhazan","doi":"10.1007/s10238-025-01724-w","DOIUrl":"10.1007/s10238-025-01724-w","url":null,"abstract":"<p><p>Aptamers, which are intricate synthetic molecules composed of single-stranded DNA and RNA, have recently emerged as groundbreaking instruments in the complex and multifaceted realms of diagnosing and treating diverse and challenging cancers, particularly leukemia, a type of blood cancer characterized by the overproduction of abnormal white blood cells. These innovative chemical antibodies, celebrated for their remarkable cost-effectiveness, unparalleled sensitivity, and exceptional precision, provide a promising beacon of hope in the arena of oncology, a field that continuously seeks novel approaches to combat various malignancies. Aptamers are fundamentally transforming the landscape of personalized medicine by adeptly and specifically targeting aberrantly expressed biomarkers, effectively modulating critical signaling pathways, and significantly enhancing the efficacy of drug delivery systems, thereby optimizing therapeutic outcomes for patients. This comprehensive review meticulously highlights the recent advancements in aptamer-based technologies, showcasing their immense potential to refine prognostic models, enhance interventions guided by the presence of minimal residual disease, and broaden the therapeutic options available for patients suffering from high-risk or relapsed forms of leukemia. Nevertheless, in conjunction with their promising applications, this study also delves into an exploration of the myriad of challenges and obstacles that may impede the realization of their full clinical potential in the healthcare setting.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"186"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism and role of ferroptosis in the development of gastric cancer.","authors":"Fang Wei, Yu Meng, Dan-Xia Zhu, Jun Wu","doi":"10.1007/s10238-025-01722-y","DOIUrl":"10.1007/s10238-025-01722-y","url":null,"abstract":"<p><p>Gastric cancer (GC) represents a prevalent form of malignant neoplasm characterized by elevated incidence and fatality rates, limited early detection capabilities, and unfavorable clinical outcomes. Its occurrence and development involve complex biological processes. As a recently identified form of cellular demise, ferroptosis has been observed across multiple cancer types, garnering significant research interest in contemporary studies. Nevertheless, the precise regulatory networks governing ferroptosis in gastric cancer, along with its functional implications in the initiation and advancement of this malignancy, remain unclear. This study seeks to elucidate the functional significance of ferroptosis in the pathogenesis of GC, systematically review the dysregulated metabolic pathways associated with this cell death process, and elucidate the intricate interactions among ferroptosis-related signaling cascades. These investigations are expected to establish a novel conceptual framework for understanding the molecular pathogenesis of gastric cancer and identifying potential therapeutic interventions. A comprehensive literature search was conducted using PubMed to identify relevant original research articles and review papers examining the molecular mechanisms underlying ferroptosis in gastric carcinoma. The search strategy incorporated the following key terms: \"Ferroptosis,\" \"Ferroptosis and gastric cancer,\" \"Ferroptosis and GSH,\" \"Ferroptosis and GPX4,\" \"Ferroptosis and system Xc-,\" \"Iron metabolism,\" \"lipid peroxidation,\" \"FSP1-CoQ10,\" \"DHODH-CoQH2,\" \"GCH1-BH4,\" \"ferroptosis inducer,\" etc. Emerging evidence from contemporary research indicates that targeted ferroptosis represents a novel and potentially efficacious treatment modality for patients with gastric cancer. Along with the identification of precise molecular targets for therapeutic intervention, the metabolic regulatory networks associated with ferroptosis remains an essential area for future research endeavors.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"182"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of immediate vs. delayed endoscopic retrieval of large or multiple common bile duct stones in high-risk elderly patients: a prospective, randomized comparative study.","authors":"Omkolsoum Alhaddad, Maha Elsabaawy, Gasser El-Azab, Ahmed Edrees, Mohamed Amer, Mohamed Eissa","doi":"10.1007/s10238-025-01712-0","DOIUrl":"10.1007/s10238-025-01712-0","url":null,"abstract":"<p><strong>Introduction: </strong>Elderly patients with common bile duct (CBD) stones often present with large or multiple stones, making endoscopic retrograde cholangiopancreatography (ERCP)-guided extraction a technically complex and potentially high-risk procedure.</p><p><strong>Aim: </strong>This study aimed to compare the efficacy and safety of a staged approach-biliary stenting followed by delayed stone extraction-versus immediate stone removal during the initial ERCP in frail elderly patients with large or multiple CBD stones.</p><p><strong>Methods: </strong>This prospective study included high-risk elderly patients with large or multiple CBD stones, defined as either a single stone ≥ 15 mm in diameter or three or more stones, each ≥ 10 mm in diameter. Participants were randomly assigned to two equal groups: Group A underwent initial biliary stenting with elective stone retrieval after 8-12 weeks, while Group B underwent immediate stone extraction during the first ERCP.</p><p><strong>Results: </strong>A total of 400 patients were included, with 200 in each group. Baseline characteristics and stone extraction methodologies were comparable between the two groups. In Group A, stone size and number significantly decreased after stenting (mean size: 1.42 ± 0.28 cm before vs. 0.98 ± 0.19 cm after stenting; P < 0.001). The overall stone clearance rate was significantly higher in Group A compared to Group B (94% vs. 80%, P < 0.001). Post-ERCP hospital stay was significantly shorter in Group A (6.41 ± 1.27 days vs. 11.3 ± 1.86 days, P < 0.001). Group B had higher rates of complications, including cholangitis (1% vs. 7%, P < 0.05) and pneumonia (2% vs. 11%, P < 0.05).</p><p><strong>Conclusion: </strong>In high-risk elderly patients with large or multiple CBD stones, temporary placement of biliary plastic stents followed by elective endoscopic stone removal effectively reduces stone size, simplifies the removal process, enhances stone clearance rates, and decreases ERCP-related complications.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"183"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the impact of CD4⁺ T cells and their subsets on relapse in AML patients during remission.","authors":"Yingxia Gu, Kai Dong, Ju Deng, Bianbian Qiao, Dan Liu, Zhifang Xu, Hongwei Wang","doi":"10.1007/s10238-025-01725-9","DOIUrl":"10.1007/s10238-025-01725-9","url":null,"abstract":"<p><p>This study investigates the impact of minimal residual disease (MRD) on relapse in patients with acute myeloid leukemia (AML), focusing on its interaction with immune cells function. A total of 49 AML patients were enrolled in this prospective study and categorized into four groups: MRD^-positive with relapse, MRD^-positive without relapse, MRD^-negative with relapse, and MRD^-negative without relapse. Peripheral blood T lymphocyte subpopulations were analyzed using ten-color flow cytometry. CD4⁺ T cells were co-cultured with leukemia cell lines to assess the impact of CD4⁺ T cells on leukemia cell proliferation, apoptosis, and cytokine release. In MRD^-positive patients, relapsed individuals exhibited significantly higher levels of CD4⁺ T cells, regulatory T (Treg) cells, and CD4⁺CD45RA⁺ naïve T cells compared to non-relapsed patients (P < 0.0001, P = 0.0016, and P = 0.0066, respectively). Conversely, in MRD^-negative patients, relapsed individuals showed a significantly lower percentage of Treg cells (P = 0.0068). Furthermore, we observed that CD4⁺ T cells were associated with enhanced leukemia cell proliferation and reduced apoptosis, along with markedly increased IL-10 expression. The available data raise the possibility that CD4⁺ T cell-derived IL-10 participates in immune microenvironment regulation, a process that may have implications for MRD maintenance and disease recurrence in AML.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"184"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two critical events in the development of the vascular system: pruning and remodeling.","authors":"Domenico Ribatti","doi":"10.1007/s10238-025-01720-0","DOIUrl":"10.1007/s10238-025-01720-0","url":null,"abstract":"<p><p>The cardiovascular system is the first functional organ system to develop in the vertebrate embryo. The primitive heart and primitive vascular plexus are formed through vasculogenesis and thereafter through angiogenesis. After the establishment of new connections within the vascular network, a pruning and remodeling process occurs after which some branches are stabilized, whereas others regress. The aim of this article is to describe the most common pruning and remodeling forms, which take place during organogenesis in the experimental and human systems.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"181"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten-year experience on home care for patients with plasma cell disorders: bringing optimal therapy home.","authors":"Flavia Bigi, Mauro Fiacchini, Roberta Restuccia, Simone Masci, Gaia Mazzocchetti, Marco Talarico, Michele Puppi, Ilaria Sacchetti, Enrica Manzato, Miriam Iezza, Katia Mancuso, Chiara Sartor, Lucia Pantani, Paola Tacchetti, Rania Abd Alatif, Erica Pastore, Simona Barbato, Michele Cavo, Elena Zamagni, Ilaria Rizzello","doi":"10.1007/s10238-025-01683-2","DOIUrl":"10.1007/s10238-025-01683-2","url":null,"abstract":"<p><p>Advanced age at diagnosis, comorbidities and invalidating symptoms can debilitate multiple myeloma (MM) and AL amyloidosis (AL) patients, potentially precluding access to optimal therapy. The Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL) has been providing home care to hematological patients in Italy since 1993. Between 2014 and 2023, 83 MM and AL patients received home infusion therapy through AIL in Bologna. Half were newly diagnosed, and half had undergone 1-7 prior lines of therapy. The median age was 79 years and 56% of patients had a performance status ≥ 2. The most frequently administered drugs included bortezomib (82%), daratumumab (14%), and bendamustine (9%). During the median 116-day therapy duration (range 1-750), patients received a median of 12 drug administrations and 12 home visits (range 1-59). Two-thirds of the patients never attended the outpatient clinic during home therapy. Ten newly diagnosed transplant-eligible patients were able to receive standard induction, restore their performance status, and proceed to transplantation. Twenty-one newly diagnosed transplant-ineligible patients received bortezomib and dexamethasone (with or without melphalan). At relapse, they were able to receive outpatient infusion therapy in 5 out of 11 cases. Elderly, frail patients, and patients in later relapse stages could maintain their quality of life, avoiding distressing hospital visits and remaining at home with their families while still receiving active treatment. Home therapy proved feasible in the 22 patients with AL in this study as well. Despite the limitations of a single-center retrospective data collection, our results show that home care in these patients is safe and feasible. We hope these preliminary findings may encourage the implementation of such programs by health policies in the future.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"179"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The necessity of adjuvant chemotherapy in young patients with T1N0M0 breast cancer: a population-based study.","authors":"Sheng Chen, Shujie Chen, Wei Cao, Xiaoyun Zhou, Min Wei, Jie Wang, Li Yang","doi":"10.1007/s10238-025-01702-2","DOIUrl":"10.1007/s10238-025-01702-2","url":null,"abstract":"","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"178"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}