OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Objective To compare the effects of sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method in thoracoscopic pulmonary segmentectomy.Methods The clinical data of 160 patients with lung cancer admitted to our hospital from January 2020 to June 2023 were retrospectively analyzed.Among them,79 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Exoview three-dimensional reconstruction and fluorescence method before the operation were classified as the Exoview group,and 81 patients who underwent thoracoscopic pulmonary segmentectomy with the sequential Mimics three-dimensional reconstruction and fluorescence method before the operation were classified as the Mimics group.The surgical completion status,the coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings,reconstruction time,segment display effect,general indicators of operation(operation time,intraoperative blood loss,number of lymph node dissection,thoracic tube placement time,postoperative hospital stay),pulmonary function[forced expiratory volume in one second(FEV1),percentage of forced expiratory volume in one second(FEV1%)]and complications were compared between the two groups.Results All patients in the two groups successfully completed thoracoscopic pulmonary segmentectomy,and indocyanine green was injected once in each group.The operation process was roughly consistent with the preoperative simulation,and no thoracotomy was performed.There was no statistically significant difference in the resection of lung segment between the two groups of patients(P>0.05).The coincidence rate between the number of left and right pulmonary artery branches evaluated before operation and intraoperative findings in the Exoview group was higher than that in the Mimics group(P<0.05).There was no significant difference in the segment display effect between the Exoview group and the Mimics group(P>0.05).The operation time and the reconstruction time in the Exoview group were shorter those that in the Mimics group,and the intraoperative blood loss was less than that in the Mimics group(P<0.05).There was no significant difference in the number of lymph node dissection,the thoracic tube placement time,or the postoperative hospital stay between the two groups(P>0.05).There was no statistically significant difference in FEV1 or FEV1%7 days after surgery compared with those before surgery(P>0.05).The FEV1 and FEV1%of patients in the Mimics group 7 days after surgery were lower than those beforesurgery(P<0.05).There was no statistically significant difference in FEV1 or FEV1%between the Exoview group and the Mimics group before and 7 days after surgery(P>0.05).The total incidence of complications in the Exoview group was 1.27%,compared with 4.94%in the Mimics group,the difference was not statistically significant(P>0.05).Conclusion Both sequential Exoview and Mimics three-dimensional reconstruction with fluorescence method are safe and effective for thoracoscopic pulmonary segmentectomy,while Exoview has more advantages in preoperative assessment of the number of pulmonary artery branches,and it has shorter reconstruction time and operation time,with less impact on lung function.

Objective:To investigate the significance of serum β2-microglobulin(β2-MG)for survival and relapse of patients with diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed.The optimal cutoff value of β2-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic(ROC)curve.Kaplan-Meier analysis was used to estimate progression-free survival(PFS)and overall survival(OS).Cox logistic regression analysis was used to explore potential prognostic factors associated with survival.Binary logistic regression analysis was used to analyze the relationship between various factors and relapse.Results:The most discriminative cutoff value for β2-MG level was determined to be 2.25 mg/L by the ROC curve.Subgroup analysis showed that patients in the elevated β2-MG(＞2.25 mg/L)group had significantly worse PFS(P=0.006)and a trend toward worse OS compared with those in the low β2-MG(≤2.25 mg/L)group(P=0.053).Univariate analysis showed that elevated β2-MG,age＞60 years,Ann Arbor stage Ⅲ-Ⅳ,as well as IPI score ≥ 3 were associated with worse PFS.Binary logistic regression analysis showed that age＞60 years and β2-M G＞2.25 mg/L were potential influencing factors for relapse of DLBCL patients.Conclusion:Serum β2-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.

Mitochondria are organelles in eukaryotic cells that play a crucial role in cellular energy me-tabolism,oxidative stress,heat production,and signal transduction.Mitochondrial transplantation(MT)is currently one of the most advanced techniques for treating mitochondrial dysfunction and anti-aging re-search.This study aimed to explore the feasibility and effectiveness of xenogeneic MT by transplanting mitochondria from yak(Bos grunniens),domestic cattle(Bos taurus),and horse(Equus caballus)into mice(Mus musculus).The results demonstrated that mitochondria from yak,domestic cattle,and horse could be successfully transplanted into mice and maintained in various tissues and organs of the mice for at least 14 days,as confirmed by confocal imaging,digital PCR,and DNA sequencing.MT mice exhibi-ted positive biological effects,including increased ATP content and mitochondrial DNA copy number(P＜0.05),with the maximum effect observed on day 7,which was sustained until day 14.Reactive oxygen species(ROS)levels in MT mice significantly increased at 2 hours post-injection(P＜0.05),then grad-ually decreased towards baseline levels by day 7 and day 14(P＞0.05).These findings support the effec-tiveness of xenogeneic MT and suggest that the effects can be maintained for up to 14 days.This study provides scientific evidence for future clinical applications.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.