Shanghai Jiao Tong University School of Medicine closely aligns with the national strategies, adheres to the Four Orientations, and practices the Four Services. Driven by problem-solving and demand-satisfying goals, we dedicate ourselves to accomplishing major scientific research tasks and reinforcing organized scientific research. We continually pool resources to strengthen original and leading scientific and technological research, enhancing our comprehensive capacity for scientific and technological innovation. Our vision is to achieve self-reliance inmedicalscience and technology, promote the advancement of medical science and technology, and make greater contributions to the development of human health. The affiliated hospitals have published several research papers in internationally renowned journals recently.
The team led by Shen Baiyong from the affiliated Ruijin Hospital published an article inCell Metabolism to reveal the complex molecular mechanism of diabetes accelerating PDAC progression
Recently, the team led by Prof. Shen Baiyong from the Department of Pancreatic Surgery, Ruijin Hospital, published an article online inCell Metabolism[IF 30.9, Q1], titled “Tumor-Associated Schwann Cell Remodeling under Metabolic Stress via Lactate Sensing Orchestrates PDAC Development”.
Their study discloses the complex molecular mechanism of diabetes accelerating PDAC progression, highlighting the core role of lactic acid in metabolic stress inducedbydiabetes-related pancreatic cancer (PDC). It is discovered that METTL16⁺CD276⁺NECTIN2⁺ Schwann cells are the key effector cell population involved in remodeling tumor-associated Schwann cells in tumor progression and immunoregulation. In diabetic patients, hyperglycemia can significantly raise the lactic acid level, thus exerting a profound impact on the tumor microenvironment. Although lactic acid is usually considered a metabolic byproduct, the above study suggests thatit also acts as a potent signaling molecule. Lactic acid is a driver of epigenetic reprogramming in TAS by activating transmethylase METTL16, which catalyzes m6A RNA modification, thereby inducing the high expression of immune escape regulators CD276 and NECTIN2. This process impairs the anti-tumor potential of CD8+ T cells and endows tumor cells with resistance to the anti-PD-1 therapy.
While most studies highlight the working mechanism of hyperglycemia, Shen’s study proposes a new pathogenic pathway: Lactic acid drives the functional transformation in TAS via METTL16-mediated m6A RNA modification. Lactic acid is the core mediator connecting metabolic imbalance and immune escape. This finding by Shen’s team fills a critical gap in the relevant research field. Their study further identifies Rosuvastatin as a potential METTL16 inhibitor. A retrospective analysis suggests that the combined use of Rosuvastatin and anti-PD-1 therapy significantly reduces tumor burden and improves clinical outcomes. Other beneficial effects include mitigating immunosuppression driven by the lactic acid-METTL16 axis, which further enhances the antitumor immune response. The above finding offers clues that inform new therapeutic strategies for PDAC with abnormal glucose metabolism. The combined use of a metabolic inhibitor and immunotherapy may be effective against tumor immune escape.
The team led by Zhou Yan and Zhao Huilin from Renji Hospital published an article in npj Digital Medicine, discussing the development of a vascular reconstruction tool based on deep learning
Recently, the team led by Zhou Yan and Zhao Huilin from the Department of Radiology, Renji Hospital, published an article innpj Digital Medicine, a global top journal in digital medicine underNature. The article is titled “Rapid vessel segmentation and reconstruction of head and neck angiograms from MR vessel wall images”. The research team collaborates with Shanghai United Imaging Healthcare Co., Ltd. They have developed a vascular reconstruction tool, VWI Assistant, based on deep learning to address the clinical bottlenecks of conventional 3D high-resolution magnetic resonance vessel wall imaging (3D MR-VWI), including time-consuming manual reconstruction and poor consistency of results.
The proposed tool has been validated in real-world clinical cohorts, spanning various disease types, centers, and MRI machines. The research teamhasintegrated VWI Assistant into uOmnispace MR Plaque Analysis, the intelligent processing software for blood vessel walls, in a seamless manner, to overcome the obstacleagainst extensible clinical applications of 3D MR-VWI. Such integration dramatically optimizes the clinical workflow and reduces labor costs, and the consistency of diagnostic results is ensured by standardized processing.All these advantages contribute to wider applications of the new technique,offering strong support for high-efficiency routine diagnosis and treatment and large-scale clinical research of cerebrovascular diseases.
VWI Assistant displays excellent performance in various disease scenarios, utilizing data from different machines. Achievingareconstruction accuracycomparable to that ofexperienced radiologists, the new tool enjoys great generalization ability andabright clinical translation prospect. VWI Assistant has been put to use at Renji Hospital. This tool significantly improves the clinical diagnostic efficiency andreducesreliance on manual reconstruction. Boasting high efficiency and standardized intelligent processing ability, VWI Assistant will promote the clinical applications of 3D MR-VWI at a greater diversity of medical institutions.
The team led by Prof. Zhang Bing, Prof. Sun Kun, and Prof. Zhu Dan from Xinhua Hospital published an article inCirculation, reporting their findingthat resurrection of endogenous retroviruses promotes myocarditis and heart failure
Recently, the team led by Prof. Zhang Bing, Prof. Sun Kun, and Prof. Zhu Dan from Xinhua Hospital published an article titled “An Aberrant Resurgence of Endogenous Retroviruses Prompts Myocarditis and Heart Failure” inCirculation. It is discovered for the first time that endogenous retroviruses (ERVs), especially the ERV1 subfamily, are resurrected in various types of heart failure. They activate Toll-like receptors (TLR) 7 and 9, the key components of the innate immune system, resulting in myocarditis and heart failure. On the contrary, inhibiting ERV resurrection or blocking ERV-induced hyperactivation of innate immunity can relieve heart failure.
To explore the role of ERV in heart failure, the authors first established an analytical method for retrotransposon RNA, which was used to analyze the total RNA transcriptome datasets of the left ventricle consisting of 78 published patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). The results showed that ERVs were significantly upregulated in myocardial tissues of heart failure patients, while other retrotransposons, such as LINE and SINE, were neither upregulated nor downregulated significantly. HERV1, a member of the ERV subfamily, was significantly upregulated in all three datasets and considered the major subtype activating ERV. The authors further demonstrated that the ERV1 subfamily was equally activated in the heart failure models in mice and non-human primates, indicating that ERV1 activation is a common molecular characteristic in several types of heart failure.
The team led by Zhao Jie and Qin’an from the Shanghai Ninth People's Hospital received approval for clinical research of China's first fibroblast injection
Recently, the Center for Drug Evaluation (CDE) published the implied approval for the Investigational New Drug (IND) application for an allogeneic human fibroblast injection. The injection is manufacturedby Shanghai-based FibroX Therapeutics, which translates the research findings of the team led by Zhao Jie and Qin’an from the Department of Orthopedics, Shanghai Ninth People’s Hospital.It is intended to treat moderate to severe lumbar intervertebral disc degenerative changes, as China’s first cellular drug against lumbar intervertebral disc degenerative changes and also among the first batch of fibroblast-targeted drugs ever approved.
Allogeneic human fibroblast injection for treating lumbar intervertebral disc degenerative changes is an industrial transformation project executed by Shanghai Ninth People’s Hospital. The scientific research findings from this project were published inBone Research, an internationally renowned journal, as a cover paper in 2020. The industrial transformation was successfully realized at the end of 2020. The team led by Prof. Zhao Jie from the Department of Orthopedics, Shanghai Ninth People's Hospital, began to collaborate with FibroX in April 2024, which marks the start ofan investigator-initiated trial (IIT).
As a common human cell type, fibroblasts secrete collagen,which plays an important role in tissue structure maintenance and wound repair. The injection is minimally invasive and reduces the risks of trauma and complications. The preclinical study showed that the intervertebral disc height recovered in animals,enhancing spinal stability and biomechanics.
The team led byLu Lungen from ShanghaiFirsGeneralt People’s Hospital published an article in Hepatology to reveal a new mechanism for liver fibrosis prevention and treatment
Recently, the team led by Lu Lungen from Shanghai First People’s Hospitalpublished an article (IF=15.8)onlineinHepatology, a leading journal in gastroenterology. The article is titled “Biliary YB-1/GLI2 axis facilitates ductular reaction and promotes hepatic stellate cell activation via SPP1/Integrin αvβ1 signaling during liver fibrogenesis”. The study proposes a new mechanism whereby bile duct reactive cells (DRCs) interact with hepatic stellate cells to promote liver fibrosis progression, and sheds some light on liver fibrosis prevention and treatment.
The team's preliminary study discovers massive DRC proliferation and ductular reaction (DR) in the portal area in patients with chronic hepatitis B and nonalcoholic steatohepatitis.Massive HSC proliferation and extracellular matrix deposition were also observed in nearby tissues. Their study demonstrates that DRC overproliferation and bile duct reaction may aggravate liver inflammation and promote HSC activation and fibrosis.
It was also found that the Y-box binding protein (YB-1) was upregulated in DRC in patients with chronic liver disease and in the mouse model of liver injury. Specific knockout of YB-1 inhibited bile duct reaction, liver inflammation, and liver fibrosis in the mouse model of liver injury. The molecular biology experiment showed that YB-1 transcriptionally regulated GLI2 expression and promoted DRC proliferation. Liquid chromatography coupled to mass spectrometry (LC–MS) identified osteopontin (SPP1) as the key molecule in YB-1/GLI2-mediated bile duct reaction that plays a role in HSC activation. Meanwhile, SPP1 was upregulated in human liver and bound to the integrin receptor. Further investigation would show that specific knockout of YB-1 inhibited DRC secretion of SPP1 and colocalization with the integrin αvβ1 receptor. However, blocking the integrin αvβ1 receptor in HSCs inhibited HSC activation, mediated by SPP1 secreted by DRC. To sum up, the YB-1/GLI2 axis promotes DRC proliferation and SPP1 secretion, which facilitates HSC activation through integrin αvβ1 receptors. This study highlights the YB-1/GLI2/SPP1 signaling pathway as a potential target for therapeutic intervention in liver fibrosis, whichcanbe used for new drug development.
The team led by Fan Cunyi from Shanghai Sixth People’s Hospital published an international clinical practice guideline for elbow joint dysfunction treatment in theJournal of Shoulder and Elbow Surgery
Recently, the team led by Prof. Fan Cunyi, the academic leader at the National Center for Orthopedics of Shanghai Sixth People's Hospital and the vice president of the Hand Surgery Branch of the Chinese Medical Association, collaborated with 10 experts in orthopedic elbow joint from Asia, Europe, and America. They jointly published a clinical practice guideline in theJournal of Shoulder and Elbow Surgery, titled “Clinical guideline on the open arthrolysis for posttraumatic elbow stiffness in adult patients”.
The development oftheguideline is initiated by the National Orthopedic Center (Shanghai/Beijing) and implemented by the Upper Limb Branch of the Asia Pacific Orthopedic Association in strict accordance with relevant standards. The evidence level is assessedfor the latest international evidenceusing the GRADE system, and the expert opinions are gathered using the Delphi method. Finally, 28 recommendations are formed concerning 13 clinical issues of greatest interest in four major aspects ofopen elbow arthrolysis, namely, indications/timing, surgical technique, perioperative management, and complication prevention. The guideline provides scientific and authoritative practical instructions fordiagnosing and treating elbow joint dysfunction.It is also the first evidence-based guideline on the orthopedic elbow joint.
