SCI,IF z-bio 2025-07-03 3290

　　As a military medical highland with a glorious history of more than 80 years, the Army Medical University (formerly the Third Military Medical University) has always adhered to the purpose of "leading medical care through war and cultivating talents for the army". This national key medical university, rooted in Chongqing, has created a monument in the fields of fighting trauma treatment, major disease prevention and control.

　　At the beginning of 2025, the school’s scientific research team intensively published a number of breakthrough results in top journals such as JAMA, Cancer Cell, Science Translational Medicine, which shows the school’s hard-core strength. The editor has selected some high-scoring articles as sharing, let’s take a look ↓↓↓

　　Key choices for stroke treatment (IF 63.1)

　　On January 13, 2025, Professor Yang Qingwu, the Second Affiliated Hospital of the Army Military Medical University, published a research paper titled "Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial" in the top medical journal JAMA.

　　This study focuses on patients with acute ischemic stroke caused by large vascular occlusion, and explores whether intra-arterial urokinase injection can improve clinical outcomes after the intravascular thrombectomy is nearly complete or complete re-enrollment. This is a randomized, open-label, end-point blind trial initiated by researchers in 35 hospitals in China. A total of 535 patients who had undergone thrombosis within 24 hours of onset, after thrombosis removal and had not undergone intravenous thrombolysis before surgery were randomly divided into intraarterial urokinase group and control group.

　　The study results showed that the 90-day disability-free survival rate in the urokinase group was 45.1%, the control group was 40.2%, and the adjusted hazard ratio was 1.13, with no statistically significant difference; there was no significant difference between the two groups at 90-day mortality rate and the incidence of symptomatic intracranial hemorrhage within 48 hours. It is concluded that in this type of patients, assisted in arterial urokinase therapy after thrombectomy cannot significantly improve 90-day disability-free survival.

　　Although the article is a negative result, it also provides Level I evidence for global stroke guidelines to avoid overtreatment.

　　On the same day, Professor Ziwenjie's team of the Second Affiliated Hospital of the Army Military Medical University also published a research paper entitled "Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke: The POST-TNK Randomized Clinical Trial".

　　Although endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke with large vascular occlusion, it is unclear whether adjuvant intra-arterial injection of tinepase can improve disability-free survival in patients with nearly complete to complete reperfusion of EVT (eTICI grade 2c-3).

　　To this end, 34 hospitals jointly conducted a POST-TNK multi-center randomized controlled trial, and included 540 patients with large vascular occlusion stroke who did not undergo intravenous thrombolysis within 24 hours of the onset and achieved high-quality reperfusion after EVT. The patients were randomly divided into two groups: the trial group (n=269) was injected with tinelapse (0.0625 mg/kg) through the catheter artery, and the control group (n=271) did not receive additional treatment.

　　The main endpoint analysis showed that the 90-day disability rate of the experimental group was 49.1%, which was only 5% absolute difference compared with the control group (44.1%), and there was no statistical significance. In terms of safety, there was no significant difference in the 90-day mortality rate (16.0% vs 19.3%) and symptomatic intracranial hemorrhage rate (6.3% vs 4.4%) in the two groups, but the incidence of imaging intracranial hemorrhage in the experimental group was significantly higher than that in the control group.

　　The study confirmed that for patients who have obtained high-quality reperfusion after EVT, additional intraarterial tinelepse cannot significantly improve the 90-day disability outcome, nor does it increase the risk of fatal bleeding, but may increase the probability of non-symptomatic intracranial hemorrhage.

　　Break through the dilemma of immunotherapy for bone metastasis (IF 48.8)

　　On April 24, Professor Zhu Bo’s team published a research paper titled “Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts” in the journal Cancer Cell, an authoritative journal in the field of oncology.

　　Although endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke with large vascular occlusion, it is unclear whether adjuvant intra-arterial injection of tinepase can improve disability-free survival in patients with nearly complete to complete reperfusion of EVT (eTICI grade 2c-3).

　　To this end, 34 hospitals jointly conducted a POST-TNK multi-center randomized controlled trial, and included 540 patients with large vascular occlusion stroke who did not undergo intravenous thrombolysis within 24 hours of the onset and achieved high-quality reperfusion after EVT. The patients were randomly divided into two groups: the trial group (n=269) was injected with tinelapse (0.0625 mg/kg) through the catheter artery, and the control group (n=271) did not receive additional treatment.

　　The main endpoint analysis showed that the 90-day disability rate of the experimental group was 49.1%, which was only 5% absolute difference compared with the control group (44.1%), and there was no statistical significance. In terms of safety, there was no significant difference in the 90-day mortality rate (16.0% vs 19.3%) and symptomatic intracranial hemorrhage rate (6.3% vs 4.4%) in the two groups, but the incidence of imaging intracranial hemorrhage in the experimental group was significantly higher than that in the control group.

　　The study confirmed that for patients who have obtained high-quality reperfusion after EVT, additional intraarterial tinelepse cannot significantly improve the 90-day disability outcome, nor does it increase the risk of fatal bleeding, but may increase the probability of non-symptomatic intracranial hemorrhage.

　　Break through the dilemma of immunotherapy for bone metastasis (IF 48.8)

　　On April 24, Professor Zhu Bo’s team published a research paper titled “Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts” in the journal Cancer Cell, an authoritative journal in the field of oncology.

　　This study used a transgenic mouse model to simulate the overactivated Wnt signaling pathway in oligodendrocyte precursor cells (OPCs) in patients with multiple sclerosis (MS), and explored its role in experimental autoimmune encephalomyelitis (EAE). The study found that in PdgfraCreER;Apcfl/fl and Olig2Cre;Apcfl/fl mice, OPCs activate Wnt signal due to the conditional knockout pathway inhibitor APC, resulting in increased expression of Wnt activation markers (such as AXIN2 and WIF1) in the spinal cord and brain of EAE mice, and intensified EAE pathological progression, manifested as enhanced T cell recruitment and an increase in a class of cytotoxic macrophage subpopulation (NK1.1+CD11b+Gr-1+), which can directly induce demyelination.

　　Further research shows that neutralizing CC chemokine ligand 4 (CCL4) through gene knockout or antibodies can inhibit CD4+ T cell infiltration and prevent disease progression; using the anti-HIV drug maraviroc approved by the European Medicines Agency antagonizes chemokine receptor 5 (CCR5), which can reduce immune cell infiltration, reduce demyelination and alleviate EAE progression. This study reveals the key role of the immune cell network regulated by OPCs in early demyelination, providing a new direction for understanding the pathological mechanism of MS and developing early intervention strategies.

　　Auditory neural circuit decoding (14.7)

　　On April 15, 2025, Chen Xiaowei, the Army Military Medical University, Sunny C. Li, Chongqing Brain and Intelligent Science Center, Liao Xiang, and Zhao Zhikai jointly published a research paper entitled "A parallel tonotopically arranged thalamocortical circuit for sound processing" in Neuron.

　　This study explored the information transmission mechanism between the mouse thalamus and the auditory cortex, and found that the basal region of the ventromedial nucleus (bVM) of the thalamus sends dense projections with tonal topological arrangements to the auditory cortex (AuC). These projections have a strong frequency tuning preference, match the tone topology of the cortex, and end primarily at neuronal-derived neurotrophic factor-positive (NDNF+) interneurons in layer 1 of the cortex, forming excitatory input.

　　Studies have shown that silencing bVM projection neurons significantly weaken the mice's ability to distinguish sound frequency and reduce the evoked response of auditory cortical neurons to sound. This discovery reveals an atypical pathway different from the classic auditory thalamic cortical pathway, where the thalamus participates in sound processing through tonal topological projection of layer 1, providing a new perspective for understanding the diversity of sensory information transmission and the regulation of cortical function.

　　Epigenetic Key for Pulmonary Hypertension (IF 16.5)

　　On February 25, Fan Ye's team from the Department of Respiratory Medicine of the Second Affiliated Hospital of the Army Military Medical University published a paper titled "ASH2L Deficiency in Smooth Muscle Drives Pulmonary Vascular Remodeling" in the journal Circulation Research.

　　This study focused on the role of histone H3 lysine 4 methylation modification in vascular remodeling of pulmonary arterial hypertension (PH) and explored the specific mechanism of ASH2L, a core member of the SET1/MLL methyltransferase complex. By analyzing human pulmonary artery specimens and vascular smooth muscle cells (SMC)-specific ASH2L knockout/overexpression animal models, combined with mass spectrometry, co-immunoprecipitation and other technologies, it was found that ASH2L in the pulmonary vessels of PH patients is the only differentially expressed member of the SET1/MLL family, and its downregulation of expression is positively correlated with the clinical severity of PH and is mainly located in SMC. Functional studies have shown that ASH2L deletion promotes SMC proliferation and vascular remodeling, while restoring its expression improves the relevant pathological phenotype.

　　Mechanistically, ASH2L does not rely on the classic H3K4 trimethylated transcriptional activation pathway, but accelerates the ubiquitin-proteasome degradation of KLF5 by forming protein complexes with KLF5 and FBXW7. The study further confirmed that NOTCH3 is a new downstream target of KLF5, and that ASH2L deletion will promote KLF5 enrichment in the NOTCH3 promoter region, enhancing its transcription. In animal models, pharmacological blockade of KLF5 can alleviate PH lesions. This study reveals that ASH2L deletion drives abnormal proliferation and vascular remodeling of SMCs through the KLF5/NOTCH3 pathway, providing a potential strategy for PH treatment to activate ASH2L or target KLF5.

　　Intelligent repair material for myocardial infarction (IF 27.4)

　　On March 7, Professor Zhu Chuhong's team from the Army Medical University and the Malcolm Xing team of the University of Manitoba, Canada, published a breakthrough research result entitled "Cardiac Organoid Model Inspired Micro-Robot Smart Patch to Treat Myocardial Infarction" at Advanced Materials.

　　This study explores the problem of limited exosome treatment effects resulting from cardiomyocyte acidosis after myocardial infarction (MI). In human cardiac organoid MI model, exosome combined with pH regulation significantly reduces cardiomyocyte mortality and maintains its proliferation potential, highlighting the importance of microenvironmental pH regulation in myocardial protection. Based on this, a microneedle (MN) patch system equipped with microrobots is proposed to target the acidic microenvironment after MI and deliver exosomes to deeply damaged tissue. After injection, the patch base releases nanoparticles loaded with vascular endothelial growth factor (VEGF) and adheres to the infarct myocardium.

　　Experiments show that this smart patch can not only reconstruct the vascular network in the MI area, but also effectively save rat cardiomyocytes. Feasibility of minimally invasive delivery of microneedle patches was verified by thoracoscopy in rabbits and pig hearts. The research results show that precise regulation of the microenvironment is the key to improving the therapeutic effect of MI. The developed MN patch system provides a new strategy that is both targeted and minimally invasive for the treatment of myocardial infarction.