Evidence map›Paper›PMID 39377966›Full record

ArticleJournal of gastroenterology2024

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.

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 and 5 more

Abstract readValidation Study
PubMed Publisher
In one paragraph

Article in Journal of gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Xin-Yue Li *Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
An-Yi Xiang *Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Xin-Yang Liu *Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Ke-Hao Wang *Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Yun WangEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Hai-Ting PanEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Ji-Yuan ZhangEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Lu YaoEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Zu-Qiang LiuEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Jia-Qi XuEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Xiao-Qing LiEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Zhao-Chao ZhangEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Wei-Feng ChenEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Ping-Hong ZhouEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China. zhou.pinghong@zs-hospital.sh.cn.
Quan-Lin LiEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China. li.quanlin@zs-hospital.sh.cn.

Funding

National Natural Science Foundation of China 82170555
6 · The paper itself

Abstract

backgroundAchalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood.

methodsWe 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.

resultsWe 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

conclusionsWe identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10

Indexed as

CytokinesEsophageal AchalasiaGenome-Wide Association StudyMendelian Randomization AnalysisMyeloid CellsSequence Analysis, RNAAdultEsophageal Sphincter, LowerFemaleHumansMaleMiddle AgedQuantitative Trait LociSingle-Cell AnalysisCytokinesAchalasiaCytokineMendelian randomizationSingle-cell RNA sequencing

Identifiers

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.