Journal of Gastroenterology最新文献

{"title":"Utility of Mac-2 binding protein glycosylation isomer as an excellent biomarker for the prediction of liver fibrosis, activity, and hepatocellular carcinoma onset: an expert review.","authors":"Yoshihiro Kamada, Yoshio Sumida, Hirokazu Takahashi, Hideki Fujii, Eiji Miyoshi, Atsushi Nakajima","doi":"10.1007/s00535-024-02179-8","DOIUrl":"https://doi.org/10.1007/s00535-024-02179-8","url":null,"abstract":"<p><p>Mac-2 binding protein glycosylation isomer (M2BPGi) is a liver fibrosis biomarker that originated in Japan and has been covered by health insurance for 10 years. M2BPGi is useful not only for liver fibrosis stage prediction but also for assessment of the degree of liver inflammation and prediction of hepatocellular carcinoma development. The usefulness of M2BPGi for assessing disease progression in patients with various chronic liver diseases has been demonstrated over the past decade in a large number of patients. Recently, there have been many reports from outside Japan, including reports from South Korea, Taiwan, Hong Kong, and China. These studies demonstrated that M2BPGi is an excellent biomarker that can evaluate the progression of liver fibrosis in chronic liver disease. It is also an excellent indicator of liver activity. Recently, a quantitative M2BPGi (M2BPGi-Qt) assay was developed, and future validation in real-world settings is expected. This will enable diagnosis of the progression of liver fibrosis based on more precise test results and is expected to contribute to the early detection and follow-up of diseases caused by chronic hepatitis, as well as post-treatment monitoring. The significance of the M2BPGi-Qt assay will likely become clearer as real-world data accumulate. If new cutoff values for each chronic liver disease stage and activity level using the M2BPGi-Qt assay are set based on real-world data, it is expected that this will become a useful tool to identify cases of liver fibrosis and monitor the progression of chronic liver disease.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standard technique in Japan for measuring hepatic venous pressure gradient.","authors":"Yusuke Imai, Yohei Koizumi, Yoichi Hiasa, Masashi Hirooka, Yoshio Tokumoto, Osamu Yoshida, Fumio Chikamori","doi":"10.1007/s00535-024-02182-z","DOIUrl":"https://doi.org/10.1007/s00535-024-02182-z","url":null,"abstract":"<p><strong>Background: </strong>Direct measurement of portal venous pressure (PVP) is invasive, so the hepatic venous pressure gradient (HVPG) is commonly measured to evaluate portal hypertension (PH). HVPG is the gold standard for estimating PVP but few reports have covered standardized measurement techniques.</p><p><strong>Methods: </strong>This study validated standardized techniques for PVP measurement.</p><p><strong>Results: </strong>In Western countries, electronic transducers are commonly used to measure PVP, whereas the water column method is still frequently applied in Japan. Setting a reference point for accurate PVP measurement is important but complicated. According to Japanese guidelines, the reference point for PVP measurement is 10 cm above the dorsal surface or in the midaxillary line. For simpler determination, the anterior axillary point, defined as the point of convergence between the proximal pectoralis major muscle and arm when both arms are positioned against the trunk in a supine position, can be used as the reference point. New methods, such as endoscopic ultrasound-guided portal pressure gradient, offer less invasive alternatives. Non-invasive methods like elastography measure liver and spleen stiffness, which correlate with HVPG. The Baveno VII criteria incorporate measurements of liver and splenic stiffness for risk stratification. Biomarkers such as type IV collagen, M2BPGi, and FIB-4 score also predict HVPG. The Baveno VII consensus emphasizes the status of HVPG as the gold standard while advocating for non-invasive alternative methods to improve patient care and monitor treatment efficacy.</p><p><strong>Conclusions: </strong>Continued development of non-invasive tests is crucial for safer, more convenient PH management.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.","authors":"Ryoichi Miura, Atsushi Ono, Hikaru Nakahara, Yuki Shirane, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Takeshi Kishi, Waka Ohishi, Naoya Sakamoto, Koji Arihiro, Clair Nelson Hayes, Shiro Oka","doi":"10.1007/s00535-024-02185-w","DOIUrl":"https://doi.org/10.1007/s00535-024-02185-w","url":null,"abstract":"<p><strong>Background: </strong>This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens.</p><p><strong>Results: </strong>In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = -0.4, p < 0.01).</p><p><strong>Conclusion: </strong>Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behçet's disease: incidence, prevalence, and real-word data on the use of biologic agents in Japan.","authors":"Tadakazu Hisamatsu, Makoto Naganuma, Philippe Pinton, Mitsuhiro Takeno","doi":"10.1007/s00535-024-02191-y","DOIUrl":"https://doi.org/10.1007/s00535-024-02191-y","url":null,"abstract":"<p><strong>Background: </strong>Behçet's disease (BD) is an autoinflammatory disease that can affect multiple organs, including the gastrointestinal tract. Conventional management comprises anti-inflammatory drugs such as glucocorticoids (GCs) and/or immunomodulators that alleviate symptoms. The introduction of biological agents that target tumor necrosis factor α (TNF-α) has improved disease management. The goal of this work was to analyze the current prevalence and incidence of total BD and gastrointestinal Behçet's disease (GIBD) in Japan, and examine treatment trends, especially regarding the use of TNF-α inhibitors (TNFαi).</p><p><strong>Methods: </strong>We performed a retrospective descriptive observational study in which BD and GIBD demographic trends, medical treatment patterns, and reported adverse events (AEs) were assessed among patients with data recorded between 2017 and 2021 in the Japan Medical Data Center Claims Database (now JMDC Inc.).</p><p><strong>Results: </strong>Prevalence of BD and GIBD in Japan during the observation period increased at an annual rate of + 3% and + 4%, respectively, while incidence decreased by - 5% and - 2%, with a more prominent decline in confirmed GIBD cases (- 15%). Although GCs were the most common initial treatment administered, use of TNFαi for BD and GIBD management increased by + 5.6% and + 8.1%, respectively. Severe AEs (mainly pneumonia and GI-associated AEs) were reported in 40% of patients receiving TNFαi; however, a high retention rate (of up to 80%) was observed 3 years after treatment initiation.</p><p><strong>Conclusion: </strong>The use of TNFαi for GIBD treatment has increased in Japan in recent years. Additional research is necessary to further evaluate TNFαi effectiveness in GIBD and other BD subtypes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors.","authors":"Shinji Okabayashi, Takahiro Itaya, Hajime Yamazaki, Ryo Yanai, Masaaki Isshiki, Yosuke Yamamoto","doi":"10.1007/s00535-024-02190-z","DOIUrl":"https://doi.org/10.1007/s00535-024-02190-z","url":null,"abstract":"<p><strong>Background: </strong>The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi.</p><p><strong>Methods: </strong>A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16 years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment.</p><p><strong>Results: </strong>We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]).</p><p><strong>Conclusions: </strong>There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of outcomes between surgery and chemoradiotherapy after endoscopic resection for pT1a-MM with lymphovascular invasion or pT1b esophageal squamous cell carcinoma: Japanese multicenter propensity score-matched study.","authors":"Yoshinobu Yamamoto, Ryu Ishihara, Hirofumi Kawakubo, Michiko Nishikawa, Sachiko Yamamoto, Tomohiro Kadota, Seiichiro Abe, Masao Yoshida, Tsutomu Tanaka, Hiroaki Nagano, Hiroyoshi Nakanishi, Tetsuya Yoshizaki, Kotaro Waki, Akiko Takahashi, Yoshiyasu Kitagawa, Kenichi Mizuno, Kenro Kawada, Yoshiyasu Kono, Chikatoshi Katada, Takashi Hashimoto, Yasuaki Nagami, Toshiyuki Yoshio, Toshio Shimokawa, Keiji Nihei, Kazuo Koyanagi, Ken Kato, Tomonori Yano, Manabu Muto, Yuko Kitagawa","doi":"10.1007/s00535-024-02188-7","DOIUrl":"https://doi.org/10.1007/s00535-024-02188-7","url":null,"abstract":"<p><strong>Background: </strong>Lymphovascular invasion (LVI) or pT1b is noncurative after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), and therefore surgery or chemoradiotherapy (CRT) is recommended. However, there has been debate regarding which treatment has better outcomes and whether individual risks should be considered.</p><p><strong>Methods: </strong>This was a multicenter, retrospective study conducted at 65 hospitals in Japan. The inclusion criteria were patients with ESCC who underwent ER between January 2006 and December 2015, with pT1a-muscularis mucosa (MM) with LVI or pT1b, with negative vertical margins, cN0M0, and who underwent surgery or CRT. A 1:1 propensity score-matched analysis was performed between two groups. The primary and secondary end points were overall survival (OS) and relapse-free survival (RFS). OS and RFS were also compared between two subgroups: low risk (pT1a-MM with LVI and pT1b without LVI) and high risk (pT1b with LVI) for metastatic recurrence.</p><p><strong>Results: </strong>Among 472 patients, 160 patients were selected from each group. The OS and RFS did not differ between surgery and CRT groups (hazard ratio, 0.887; P = .635 and hazard ratio, 1.036; P = .876, respectively). Subgroup analysis showed that CRT had a better prognosis in the low-risk group, and conversely, surgery had a better prognosis in the high-risk group. But these were not significant. The high-risk CRT group had a significant worse prognosis than the low-risk CRT group.</p><p><strong>Conclusions: </strong>In patients with noncurative ER for ESCC, surgery and CRT showed no difference in long-term outcomes. Indications for CRT in the high-risk group need further investigation because of poor prognosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter to the editor regarding: \"Alcohol-associated liver disease increases the risk of muscle reduction and mortality in patients with cirrhosis\".","authors":"Tatsunori Hanai, Kayoko Nishimura, Shinji Unome, Takao Miwa, Yuki Nakahata, Kenji Imai, Atsushi Suetsugu, Koji Takai, Masahito Shimizu","doi":"10.1007/s00535-024-02153-4","DOIUrl":"10.1007/s00535-024-02153-4","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1144-1145"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.","authors":"Lawan Rabiu, Pengchao Zhang, Lukman O Afolabi, Muhammad A Saliu, Salisu M Dabai, Rabiatu B Suleiman, Khalid I Gidado, Mark A Ige, Abdulrahman Ibrahim, Guizhong Zhang, Xiaochun Wan","doi":"10.1007/s00535-024-02157-0","DOIUrl":"10.1007/s00535-024-02157-0","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a multifaceted liver disease characterized by inflammation and fibrosis that develops from simple steatosis. Immune and inflammatory pathways have a central role in the pathogenesis of MASH, yet, how to target immune pathways to treat MASH remains perplexed. This review emphasizes the intricate role that immune cells play in the etiology and pathophysiology of MASH and highlights their significance as targets for therapeutic approaches. It discusses both current strategies and novel therapies aimed at modulating the immune response in MASH. It also highlights challenges in liver-specific drug delivery, potential off-target effects, and difficulties in targeting diverse immune cell populations within the liver. This review is a comprehensive resource that integrates current knowledge with future perspectives in the evolving field of MASH, with the goal of driving forward progress in medical therapies designed to treat this complex liver disease.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1053-1078"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.","authors":"Zhizhong Xiong, Xianzhe Li, Minghao Xie, Jianping Guo, Shi Yin, Dayin Huang, Longyang Jin, Caiqin Wang, Fengxiang Zhang, Chaobin Mao, Huaxian Chen, Dandong Luo, Haijie Tang, Xijie Chen, Lei Lian","doi":"10.1007/s00535-024-02152-5","DOIUrl":"10.1007/s00535-024-02152-5","url":null,"abstract":"<p><strong>Background: </strong>Intestinal fibrosis is one of the most frequent and severe complications of Crohn's disease. Accumulating studies have reported that adipose mesenchymal stem cell-derived small extracellular vesicles (AMSC-sEVs) could alleviate renal fibrosis, hepatic fibrosis, etc., while their potential for treating intestinal fibrosis remains uncertain. Therefore, this study aims to determine the therapeutic effects of AMSC-sEVs on intestinal fibrosis and identify the mechanisms underlying these effects.</p><p><strong>Methods: </strong>AMSC-sEVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blot. Whether AMSC-sEVs exert antifibrotic effects was investigated in two different murine models of intestinal fibrosis. Besides, AMSC-sEVs were co-cultured with primary human fibroblasts and CCD18co during transforming growth factor (TGF)-β1 stimulation. Label-free proteomics and rescue experiments were performed to identify candidate molecules in AMSC-sEVs. Transcriptome sequencing revealed changes in mRNA levels among different groups. Lastly, proteins related to relevant signaling pathways were identified by western blotting, and their expression and activation status were assessed.</p><p><strong>Results: </strong>AMSC-sEVs positively expressed CD63 and Alix and presented a classical \"rim of a cup\" and granule shape with approximately 43-100 nm diameter. AMSCs significantly alleviated intestinal fibrosis through secreted sEVs in vitro and in vivo. The milk fat globule-EGF factor 8 (MFGE8) was stably enriched in AMSC-sEVs and was an active compound contributing to the treatment of intestinal fibrosis by AMSCs. Mechanistically, AMSC-sEV-based therapies attenuated intestinal fibrosis by inhibiting the FAK/Akt signaling pathway.</p><p><strong>Conclusions: </strong>MFGE8-containing AMSC-sEVs attenuate intestinal fibrosis, partly through FAK/Akt pathway inhibition.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1092-1106"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of circulating cytokine levels and tissue-infiltrating myeloid cells with achalasia: results from Mendelian randomization and validation through clinical characteristics and single-cell RNA sequencing.","authors":"Xin-Yue Li, An-Yi Xiang, Xin-Yang Liu, Ke-Hao Wang, Yun Wang, Hai-Ting Pan, Ji-Yuan Zhang, Lu Yao, Zu-Qiang Liu, Jia-Qi Xu, Xiao-Qing Li, Zhao-Chao Zhang, Wei-Feng Chen, Ping-Hong Zhou, Quan-Lin Li","doi":"10.1007/s00535-024-02155-2","DOIUrl":"10.1007/s00535-024-02155-2","url":null,"abstract":"<p><strong>Background: </strong>Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms.</p><p><strong>Results: </strong>We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20-6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59-0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10^high monocytes in achalasia displayed activated type I interferon signaling, and IL1RN^low FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia.</p><p><strong>Conclusions: </strong>We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10^high monocytes and IL1RN^low macrophages may play a role in the pathogenesis of achalasia.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1079-1091"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}