Groundbreaking Discovery: Shanghai Children’s Medical Center Unveils New Mechanism in B-ALL Leukemia Progression
A collaborative team from the Department of Clinical Nutrition, Hematology and Oncology, and the Institute of Pediatric Translational Medicine at Shanghai Children’s Medical Center recently published a major study inInternational Journal of Cancer. The paper, titled "Bone Marrow Adiposity Caused by GREM1 Deficiency Promotes Pediatric B-ALL Progression", is the first to reveal a critical link between dyslipidemia, bone marrow adiposity, and the progression of pediatric B-cell acute lymphoblastic leukemia (B-ALL). It also identifies GREM1 as a key regulator in lipid metabolism remodeling. This discovery provides a novel scientific foundation for targeted therapies and nutritional interventions for leukemia, with significant implications for tackling treatment resistance and relapse.
Led by Professor Hong Li, the team has long focused on body composition and metabolic changes in pediatric leukemia patients. They found that patients may exhibit fat accumulation and lipid metabolism disorders, though mechanisms remained unclear. Their research confirms that dyslipidemia and bone marrow adiposity are major factors in refractory and relapsed B-ALL. Through RNA sequencing, they identified GREM1 as a crucial regulator of adipogenic differentiation in bone marrow mesenchymal stem cells (BM-MSCs). Its deficiency activates the BMP-SMAD signaling pathway, accelerating leukemia progression.
Shanghai Children’s Hospital Team Publishes Rare Case of Juvenile Ménétrier’s Disease inThe New England Journal of Medicine
Professor Liu Haifeng and his team at the Digestive Endoscopy Center of Shanghai Children’s Hospital published a highlighted case report in the world-renowned medical journalThe New England Journal of Medicine (NEJM) titled "Ménétrier’s Disease." The report describes a rare juvenile case that presented solely with generalized edema and hypoalbuminemia—without gastrointestinal symptoms—and was diagnosed through multidisciplinary collaboration among the Digestive Endoscopy Center, Nephrology and Rheumatology, Radiology, and Pathology departments.
Ménétrier’s disease is a rare idiopathic condition marked by gastric mucosal hypertrophy and protein-losing gastroenteropathy, with an incidence in children of less than one in a million. This case represents the hospital’s first publication in NEJM and highlights its global leadership in pediatric rare digestive disorders. Professor Liu’s team has treated over 100 cases of rare pediatric gastrointestinal diseases, supported by the hospital’s Precision Diagnosis and Treatment Center for Pediatric Rare Diseases.
Shanghai Chest Hospital Unveils Promising New Combination Therapy for Advanced NSCLC
The Department of Pulmonary and Critical Care Medicine at Shanghai Chest Hospital published new findings in theInternational Journal of Cancer titled "Efficacy and safety of autologous CIK cell therapy plus Toripalimab with or without chemotherapy in advanced NSCLC: A phase II study." This study examines a novel combination therapy using cytokine-induced killer (CIK) cells and the PD-1 inhibitor Toripalimab, with or without chemotherapy, for treating advanced non-small cell lung cancer (NSCLC).
Lung cancer accounts for over 80% of lung cancer cases, which remain a leading cause of cancer death in China and globally. While immunotherapies such as PD-1/PD-L1 inhibitors have shown promise, their efficacy is limited by poor T-cell infiltration in tumors. CIK cells, combining T cell and NK cell characteristics, show broad anti-tumor activity. This study enrolled 40 patients with PD-L1-positive, driver gene-negative advanced NSCLC. Results showed that while both treatment arms (Toripalimab + CIK ± chemotherapy) had high disease control rates (>90%), the triple combination (with chemotherapy) significantly improved progression-free survival (PFS: 20.0 vs 6.0 months) and overall survival. Patients receiving ≥4 cycles of CIK therapy also had better outcomes. The findings suggest the triple therapy is effective and safe, offering a new treatment avenue for advanced NSCLC.
Shanghai Mental Health Center Develops Deep Learning Model for Early Warning of Mild Cognitive Impairment
Recently, a research team led by Professors Xiao Shifu and Yue Ling from Shanghai Mental Health Center in collaboration with Professors Shen Dinggang and Pan Yongsheng from ShanghaiTech University, published their latest study titled“Predicting cognitive decline: Deep-learning reveals subtle brain changes in pre-MCI stage” in theJournal of Prevention of Alzheimer’s Disease. The study successfully developed a predictive model for Mild Cognitive Impairment (MCI), providing a new method for early identification of cognitive disorders.
The model is based on magnetic resonance imaging (MRI) data and is built on a deep learning training framework. It utilizes a multi-ROI-based network (MRNet) to screen and integrate features from ten brain regions with high discriminative power, including the hippocampus, amygdala, and cerebellum. A Progressive Index (PI) was then constructed. This index, derived from a deep learning-based continuous quantitative assessment system, analyzes MRI brain images to generate a risk score within the range of [0, 1]; the higher the score, the greater the risk of future progression to cognitive impairment. This index breaks through the limitations of traditional binary diagnoses and enables dynamic monitoring of intermediate stages of neurodegenerative diseases such as Alzheimer’s.
Figure 1: Research workflow diagram
Figure 2: Top 10 most discriminative brain regions for MCI prediction based on deep learning
To further evaluate the predictive power of the PI for cognitive impairment risk, the research team integrated demographic information, neuropsychological assessments, and PI scores from MRI scans to establish an MCI prediction model. The model effectively predicted progression to MCI over a seven-year follow-up in the CLAS cohort.
Figure 3: Model prediction performance
Significance: With the recent clinical approval and application of disease-modifying therapies such as Lecanemab and Donanemab, the MCI and mild dementia stages have become a critical window for Alzheimer’s intervention. Therefore, this study is particularly important for the early prediction of cognitive disorders. It aids in identifying potential patients and offers the possibility for timely and effective treatment to slow disease progression and improve prognosis.
Research from the International Peace Maternity & Child Health Hospital Offers Valuable Insight into How Early-Life Environmental Exposure Affects Allergic Disease Development in Infants
Adverse early-life exposures are closely associated with both short- and long-term health outcomes. Atopic dermatitis (AD) is the most common allergic disease in infants and often represents the earliest manifestation of the allergic march. The prevalence of AD continues to rise in China, yet its pathogenesis remains unclear. Increasing evidence suggests that environmental changes in early life significantly impact the development of AD.
Recently, Professor Liu Zhiwei from the International Peace Maternity & Child Health Hospital published a letter inAllergy titled “Early-Life Quarantine Increases the Development of Infant Atopic Dermatitis: A Birth Cohort Study in China”. During the COVID-19 pandemic, strict public health measures such as lockdowns, mask-wearing, and frequent handwashing significantly altered infants’ environmental exposures in early life. However, the impact of these changes on AD incidence remains unclear.
Based on a previously established birth cohort, the study divided 2,204 mother-infant pairs into two groups according to whether the infant experienced the pandemic control measures during early life (from pregnancy to 6 months of age): the non-quarantine group (infants who turned 6 months old before December 31, 2019, n = 1,409) and the quarantine group (infants whose mothers’ last menstrual period occurred around December 31, 2019, n = 795). Using multivariable logistic regression, propensity score matching (PSM, 1:1), and inverse probability of treatment weighting (IPTW), the study assessed the effect of early-life pandemic control measures on the development of eczema. Results showed that infants who experienced these measures had a significantly higher risk of developing eczema by 6 months of age (OR: 2.27–2.93). The study does not intend to criticize the control measures but rather highlights the need for increased attention to the growing burden of allergic diseases in infants. It provides valuable insight into how early-life environmental exposures may influence allergic disease development.
Tongren Hospital Team Reveals Mitochondrial Iron Metabolism as a Potential Target for Slowing Osteoarthritis Progression
A research team led by Drs. Ye Xiaojian and Li Xiaoxiao from the Department of Orthopedics at Tongren Hospital recently published a paper inAdvanced Healthcare Materials titled “β-Diketone Functionalized Microspheres Chelate Reactive Iron via Metal Coordination for Cartilage Repair.”
This study focuses on the prevention and treatment of chondrocyte ferroptosis. The team developed a multi-level composite system using microfluidics and nanotechnology aimed at restoring mitochondrial homeostasis to protect cartilage and treat osteoarthritis (OA). The system features cartilage-targeted polymeric micelles (P-PTPC) as secondary nanostructures embedded within GelMA hydrogel microspheres (Gel@P-PTPC), forming a stable microsphere composite.
The researchers first synthesized a ROS-sensitive polymer (PEG-TK-PLLA) with a thioketal (TK) linker via ring-opening polymerization and in-situ amide bonding, and conjugated it with a collagen type II-targeting peptide to obtain cartilage-targeted block copolymers (P-PTP). Then, hydrophobic interactions and solvent evaporation were used to prepare P-PTPC micelles loaded with curcumin. Finally, using microfluidics, P-PTPC was encapsulated into GelMA hydrogel microspheres to create a sustained-release multi-level microsphere structure (Gel@P-PTPC).
The 3D network of the microspheres acts as a physical barrier, limiting micelle diffusion and extending drug retention. Slowly released P-PTPC targets chondrocytes and enters the cells via endocytosis. In high-ROS environments, TK groups are cleaved, exposing the β-diketone structure of curcumin, which chelates excess intracellular reactive iron. This, along with activation of the Nrf2/GPX4 pathway, reduces lipid peroxidation, restores mitochondrial homeostasis, and inhibits ferroptosis, thereby mitigating cartilage damage.
This study proposes a novel material-based strategy for restoring mitochondrial iron metabolism and antioxidant capacity, offering a new theoretical foundation and therapeutic approach for OA and related diseases driven by ferroptosis.
Songjiang Hospital Researchers Reveal Role of Neuron-Derived Slit1 in Promoting Myelination under Chronic Hypoxia
A recent study by Professor Zhang Liang from Songjiang Hospital/Research Institute, in collaboration with Professor Zhang Xueqin from Xiamen University Women and Children's Hospital, was published inCell Reports titled “A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.”
This study is the first to report that under hypoxic white matter injury (WMI) conditions, neuron-secreted axon guidance molecule Slit1 promotes oligodendrocyte progenitor cell (OPC) differentiation through the Robo2–srGAP1–RhoA signaling pathway, playing a key role in maintaining white matter integrity.
Chronic prenatal hypoxia is a major cause of WMI in newborns, which suppresses myelination and leads to long-term neurological impairments. However, the underlying pathological mechanisms remain unclear. Using a chronic hypoxia mouse model (postnatal days 3–10 exposed to 10% O?) and brain tissue from asphyxiated neonates, the researchers found significantly reduced expression of myelin basic protein (MBP) in various brain regions, with lasting hypomyelination and motor/cognitive impairments. Proteomic analysis revealed upregulation of the Slit-Robo pathway after hypoxia, with Slit1 highly expressed in neurons.
Interestingly, constitutive knockout of Slit1 did not affect normal myelination during development. However, under chronic hypoxia, both Slit1 knockout and neuron-specific Slit1 knockout mice exhibited worsened myelination defects and fewer mature oligodendrocytes. Further in vitro studies using recombinant Slit1 or neuron–OPC co-cultures confirmed Slit1’s essential role in promoting myelination under hypoxia. Mechanistically, Slit1 binds to Robo2, regulating the srGAP1–RhoA pathway to promote OPC differentiation.
Notably, pharmacological targeting of RhoA rescued hypoxia-induced synaptic density loss and improved both myelination and motor/cognitive function in hypoxic mice. This study highlights a neuron-derived Slit1-dependent signaling pathway critical for hypoxic myelination, suggesting a promising therapeutic target for WMI in preterm infants. Moreover, adaptive genetic variations in the SLIT1 gene identified in the Tibetan population offer new insights into human adaptation to hypoxic environments.
