JOURNAL OF CLINICAL INVESTIGATION临床研究杂志
JOURNAL OF CLINICAL INVESTIGATION(英文缩写 J CLIN INVEST),ISSN 0021-9738,eISSN 1558-8238,中文译名:临床研究杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 19.477 | Q1 |
| 2022 | 15.900 | Q1 |
| 2023 | 13.300 | Q1 |
| 2024 | 13.600 | Q1 |
| 2025 | 14.300 | Q1 |
JOURNAL OF CLINICAL INVESTIGATION 最新收录文献
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1. Neuronal and non-neuronal TRPA1 mediate distinct pain perception mechanisms in Familial Episodic Pain Syndrome models.
1. 神经元和非神经元TRPA1在家族性发作性疼痛综合征模型中介导不同的疼痛感知机制PMID:日期:2026-10-01Familial Episodic Pain Syndrome (FEPS) is a rare inherited disorder characterized by recurrent episodes of severe upper-body pain triggered by stimuli such as cold, stress, or fasting. A gain-of-function mutation (N855S) in the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel has been identified in affected individuals, yet the cellular mechanisms driving FEPS pain remain poorly defined. Although TRPA1 has been primarily studied in sensory neurons, emerging evidence suggests that non-neuronal cells may contribute to pain signaling. To define the cell-specific role of mutant TRPA1 (TRPA1mut), we generated mouse models selectively expressing TRPA1mut in Schwann cells or sensory neurons, using CRISPR-based and Cre-loxP strategies. Patch-clamp recordings confirmed enhanced agonist-evoked currents in TRPA1mut compared with wild-type channels. Behavioral analyses revealed that neuronal TRPA1mut mediates acute nociceptive responses, whereas Schwann cell TRPA1mut drives mechanical allodynia induced by subthreshold TRPA1 agonists and physiological triggers relevant to FEPS, including fasting, cold exposure, and restraint stress. These responses were associated with increased reactive oxygen species and accumulation of 4-hydroxynonenal in sciatic nerves and were attenuated by antioxidant treatment. These findings uncover a previously unrecognized Schwann cell-dependent mechanism of TRPA1-driven pain and identify non-neuronal TRPA1 signaling as a potential therapeutic target in FEPS and related pain channelopathies.
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3. Corrigendum to Insulin-like growth factor 2 drives fibroblast-mediated tumor immunoevasion and confers resistance to immunotherapy.
3. 胰岛素样生长因子2驱动成纤维细胞介导的肿瘤免疫逃逸并赋予免疫治疗耐药性的更正PMID:日期:2026-10-01该文献暂无摘要。
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4. Corrigendum to An inherited predisposition allele promotes gastric cancer via enhancing deubiquitination-mediated activation of epithelial-to-mesenchymal transition signaling.
4. 遗传易感等位基因通过增强去泛素化介导的上皮-间质转化信号激活促进胃癌发生的勘误PMID:日期:2026-10-01该文献暂无摘要。
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5. Corrigendum to Genetic modification of inflammation- and clonal hematopoiesis-associated cardiovascular risk.
5. 炎症和克隆性造血相关心血管风险的基因修饰更正PMID:日期:2026-10-01该文献暂无摘要。
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6. Tie1 ectodomain cleavage governs vascular responses to inflammatory stimulation but is dispensable for angiogenic signaling.
6. Tie1胞外域切割调控血管对炎症刺激的反应，但对血管生成信号传导并非必需PMID:日期:2026-10-01Ectodomain cleavage of the vascular receptor Tie1 distinguishes the inflammatory from the angiogenic functions of Angiopoietin-Tie signaling, mechanistically uncoupling two fundamental vascular programs.
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7. Loss of Smad4 drives vascular malformations via c-KIT-dependent high-fluid shear stress mimicry.
7. Smad4缺失通过c-KIT依赖的高流体剪切应力模拟驱动血管畸形PMID:日期:2026-10-01Vascular endothelial cells (ECs) encode a homeostatic fluid shear stress (FSS) set point that is essential for vascular stability. Deviations above or below this threshold trigger adaptive remodeling to restore physiological shear levels. Disruption of this control mechanism leads to enlarged arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia, a vascular disorder caused by heterozygous loss-of-function (LOF) mutation in ALK1, ENG, or SMAD4. Mechanistically, Smad4-deficient ECs are reset to a lower FSS set point value, resulting in AVMs that show characteristics of high-FSS remodeling with elevated KLF4 and high activation of the downstream Akt. Here, we investigated the KLF4/Akt upstream mechanisms by which SMAD4 sets the physiological FSS set point. We identified the receptor tyrosine kinase c-KIT as a component and regulator of the junctional mechanosensory receptor complex, which is highly upregulated in murine and human AVMs. SMAD4 restrains flow signaling by limiting c-KIT-dependent ERK5 activation and KLF4 induction. Thus, SMAD4 LOF leads to sustained c-KIT engagement in the sensory junctional apparatus, driving enhanced and prolonged activation of the ERK5/KLF4/Akt signaling axis. These results show that Smad4-LOF mutations induce malformations by disabling a key homeostatic mechanism and identify c-KIT as a potentially previously unrecognized therapeutic target.
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8. c-KIT expands the tool kit for treating arteriovenous malformation.
8. c-KIT拓展了治疗动静脉畸形的工具库PMID:日期:2026-10-01Hereditary hemorrhagic telangiectasia (HHT) is characterized by fragile, enlarged vessels with arteriovenous connections, which can form arteriovenous malformations (AVMs) that are prone to rupture. It is driven by mutations in TGF‑β pathway genes that disrupt endothelial cell responses and blood vessel remodeling. Two studies published in this issue of the JCI identify c‑KIT as a central mediator of HHT vascular pathology. Gahn et al. showed that SMAD4 loss derepressed c‑KIT, whose activity in the junctional mechanosensory receptor complex of endothelial cells reset the fluid shear stress set point to drive maladaptive vascular remodeling. Drapé et al. demonstrated that ALK1 loss in a mouse model of HHT induced a regional pro‑angiogenic c‑KIT+ endothelial state in brain AVMs. Both studies showed that pharmacologic c-KIT inhibition mitigated disease, revealing an unexpected, potentially ligand‑independent role for c‑KIT and highlighting a promising therapeutic target.
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9. Antibody-drug conjugates in breast cancer: redefining targeted therapy.
9. 抗体药物偶联物在乳腺癌中的应用：重新定义靶向治疗PMID:日期:2026-10-01Antibody-drug conjugates (ADCs) have transformed the treatment landscape of breast cancer and redefined the conceptual distinction between targeted therapy and conventional chemotherapy. Originally conceived as "magic bullets" that selectively deliver cytotoxic warheads to antigen-expressing tumor cells, clinical and mechanistic evidence indicates that ADC activity depends on a broader interplay of target-dependent and target-independent mechanisms, including extracellular payload release, bystander killing, off-tumor uptake, and immune modulation. Here, we examine ADCs in breast cancer as a distinct therapeutic paradigm. We discuss how antigen biology, linker chemistry, payload features, and drug-to-antibody ratio collectively determine efficacy, toxicity, and therapeutic index. We then compare currently approved and emerging HER2- and TROP2-directed ADCs, highlighting how differences in linker stability, payload pharmacology, and bystander capacity can affect clinical outcomes in ADCs sharing the same target. We further discuss the biological basis and translational challenges of de novo and acquired resistance related to targets, payloads, and tumor microenvironmental constraints, as well as the implications of these mechanisms for biomarker development, sequencing rationales, and combination strategies with immune checkpoint inhibitors and DNA repair-targeting therapies. Finally, we outline future directions of ADC development, including expansion of the target space, novel payload modalities, and next-generation antibody and conjugation engineering.
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10. All in the family: a population-scale perspective on genetic networks of autoimmune disease.
10. 家族遗传：自身免疫性疾病基因网络的人群尺度视角PMID:日期:2026-10-01Autoimmune diseases share a genetic predisposition, and GWAS have identified certain HLA haplotypes as components of susceptibility. In this issue of the JCI, Eriksson et al. leveraged population-scale registry data from Sweden, encompassing 6.3 million individuals in combination with paired relatedness data from a remarkable 3.84 million sibling pairs drawn from 1.57 million nuclear families to create a unified model of the shared genetic risk across 22 common and rare autoimmune diseases. The resulting network of pairwise genetic relationships demonstrated that genetic predisposition alone could not explain the full spectrum of autoimmunity. Analyses exposed distinct patterns, confirmed expected genetic relationships, and revealed unexpected findings. By looking into the family to quantify shared genetic liability at a remarkable scale, this study not only reinforces established genetic components of autoimmune disease but also highlights variation that lacks shared genetic architecture, paving the way for future study of environmental mechanisms in autoimmunity.