Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.

[摘 要] 目的：基于生物信息学方法探究几丁质酶-3样蛋白2（CHI3L2）在脑胶质瘤中的表达和生物学过程及其对患者临床预后的影响。方法：以中国脑胶质瘤基因组图谱（CGGA）为训练集（n = 325）、癌症基因组图谱（TCGA）为验证集（n = 702），对CHI3L2与脑胶质瘤患者临床病理特征的关系、预后价值和生物学过程进行交叉验证分析。用Kaplan-Meier法进行生存分析，采用Cox回归模型分析CHI3L2表达及相关临床病理特征与脑胶质瘤患者预后的关系，利用受试者工作特征（ROC）曲线分析CHI3L2在脑胶质瘤诊断中的价值，用GO、KEGG及GSVA途径分析CHI3L2在脑胶质瘤中的潜在生物学过程，构建CHI3L2的列线图以校准曲线及C-Index值来评估预测的准确性。WB法和qPCR 法检测CHI3L2在正常星形胶质细胞HA1800、胶质瘤U215和U87细胞中蛋白质与mRNA水平表达的影响。选取长沙市中心医院病理科保存的7例正常脑组织、5例低级别胶质瘤（LGG, WHOⅠ~Ⅱ级）和6例胶质母细胞瘤（GBM，WHO Ⅳ级）标本进行免疫组化染色分析，验证CHI3L2在正常脑组织和不同级别脑胶质瘤组织中的表达情况。结果：CHI3L2在GBM（P < 0.000 1）、非1p/19q编码（P < 0.000 1）、IDH-野生型（P < 0.000 1）、非MGMT甲基化（P<0.01）患者中显著表达，对GBM具有一定的预测价值，并且是脑胶质瘤患者总生存期（OS）的独立预后因素（P < 0.001）。构建的列线图对脑胶质瘤患者的生存预后预测性良好。CHI3L2与LGG和GBM的免疫细胞浸润水平、肿瘤免疫微环境和免疫细胞均有显著关系。脑胶质瘤中CHI3L2蛋白（P < 0.05）和mRNA（P < 0.000 1）的表达水平与更高的恶性程度相关，免疫组化的结果进一步验证了这个发现。结论：CHI3L2的表达与脑胶质瘤的恶性程度、临床病理特征及预后关系密切，并且参与脑胶质瘤的肿瘤微环境和免疫浸润，有望成为脑胶质瘤治疗策略中的一个新靶点。

Patients with gastric cancer are at high risk for venous thromboembolism(VTE)and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.

Patients with primary membranous nephropathy(PMN)tend to develop thrombosis,especially in the early phase of the disease.The pathogenesis of thrombosis is multifactorial,with hypoalbuminemia being widely regarded as an inde-pendent risk factor.Other factors include proteinuria,M-type phospholipase A2 receptor antibody,and D-dimer.Although prophy-lactic anticoagulation therapy is frequently used in clinical practice to prevent thrombosis in PMN patients,there are still many un-resolved issues regarding the optimal prevention of thrombosis in this condition.The timing of prophylactic anticoagulation,the threshold of serum albumin level,and the choice of treatment regimen are still lacking consensus.This article reviewed the relevant literature on these topics,aiming to establish a standard for thrombosis prevention and treatment for this population in the future and provide guidance for clinical practice.

ObjectiveTo analyze the correlation between 11 small molecule active components and 1 protein component of characteristic processed products with porcine cardiac blood and other products of Salviae Miltiorrhizae Radix et Rhizoma（SMRR） from Menghe medical school and anti-cerebral ischemic oxidative damage， and to identify its key component markers of characteristic processed products with porcine cardiac blood for anti-cerebral ischemic oxidative damage. MethodHigh performance liquid chromatography（HPLC） was established to simultaneously determine the contents of 11 active ingredients in SMRR and its processed products［processed with porcine cardiac blood， porcine blood， wine and transferrin（Tf） in porcine cardiac blood］， and the content of Tf in different processed products of SMRR was detected by enzyme-linked immunosorbent assay（ELISA）. Furthermore， A zebrafish ischemic stroke model was constructed to evaluate the effects of different processed products of SMRR on the behavioral trajectory of cerebral ischemic zebrafish， the neuronal damage of transgenic zebrafish Tg（elavl3：eGFP） brain， as well as the levels of malondialdehyde（MDA） and superoxide dismutase（SOD） in the brain tissues. The hippocampal neurons oxygen-glucose deprivation/reoxygenation（OGD/R）-induced ischemia-hypoxia model was constructed to evaluate the effects of different processed products of SMRR on oxidative damage of neuronal cells by taking lactate dehydrogenase（LDH）， reactive oxygen species（ROS）， MDA and SOD as indexes. Finally， principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used to analyze the 11 small molecule active components and 1 protein component with efficacy indicators， in order to screen the key components of the characteristic processed products with porcine cardiac blood for cerebral ischemic oxidative damage. ResultCompared with the raw products， the contents of water-soluble and fat-soluble components in processed products of SMRR increased to different degrees， while the content of salvianolic acid A decreased. Compared with the wine-processed products， the contents of salvianolic acid B， danshensu， rosmarinic acid and other components in the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products were increased， while the content of salvianolic acid A was decreased. ELISA results showed that there was no significant difference in Tf content between the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products. Pharmacological results showed that different processed products of SMRR could improve the behavioral deficits， brain neuronal injury and oxidative stress after ischemic stroke in zebrafish， and the effect of the porcine cardiac blood-processed products was most pronounced. PCA results showed that salvianolic acid B， salvianolic acid A， rosmarinic acid， lithospermic acid， danshensu， tanshinone Ⅱ_A， caffeic acid， cryptotanshinone and tanshinone Ⅰ were the main contributing components of SMRR and its processed products. And the results of correlation analysis showed that the contents of cryptotanshinone， rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A and tanshinone Ⅰ were negatively correlated with MDA level in zebrafish brain tissue， while the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B and Tf were positively correlated with SOD level， and the contents of rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A， tanshinone Ⅰ， danshensu， Tf were positively correlated with neuronal fluorescence intensity in the zebrafish brain. And the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone Ⅱ_A and Tf were negatively correlated with LDH， ROS and MDA levels and positively correlated with SOD level. ConclusionThere are differences in the anti-ischemic oxidative damage effects of SMRR and its different processed products， among which the porcine cardiac blood-processed products has the strongest effect on improving oxidative damage， which may be related to the content changes of salvianolic acid B， danshensu， rosmarinic acid and other components. This study can provide a basis for clarifying the quality markers of SMRR processed with porcine cardiac blood for cerebral ischemia and elucidating its processing mechanism.

Objective To establish the quantitative evaluation system on the internal control of drug management, which could reflect the improvement and optimization of the internal control of drug management and be reference for the drug management in the hospital. Methods Brainstorm method was used to design a quantitative evaluation table. The methods of walking test, field inspection and comparative analysis were used to carry out the internal control design and execution effectiveness evaluation. Results Evaluation score increased from 36.50 points in 2015 to 43.75 points in 2021 when the full score was 50 points. The proportion of drug intotal income decreased from 37.97% in 2015 to 21.62% in 2021.The drug markup rate decreased from 14.38% to 0.96%, and the intensity of antibiotic DDDs decreased from 55.48 in 2018 to 39.30 in 2021. The proportion of essential drug prescriptions was higher than the national examination data. Conclusion The optimizing quantitative evaluation system on the internal control of drug management could improve the management specialization, the structure of income and payout and the level of rational drug use, promote the high-quality development of hospitals and safeguard the implementation of the Healthy China strategy.

The incidence of gastric cancer ranks fifth among malignant tumors worldwide, with the fourth highest mortality rate. A noteworthy characteristic of our country is the high prevalence of advanced-stage patients of approximately 40%. Advanced-stage gastric cancer carries an unfavorable prognosis with median survival of around one year. Diagnosis methods for advanced-stage gastric cancer (such as laparoscopic exploration, molecular profiling, and artificial intelligence) are still being continuously improved, while chemotherapy remains the primary treatment. With the rapid development of medical science, the role of surgical intervention in advanced-stage gastric cancer is becoming increasingly prominent. Therefore, as gastric tumor surgeons, we should consider how to use a combination of treatments, including surgery, chemotherapy, targeted therapy, immunotherapy, and interventional therapy, based on different pathological stages and the heterogeneity of tumors. With a multidisciplinary approach involving experts from various fields, we can collectively improve the survival rate and quality of life for advanced-stage patients. This article provides a brief overview of the current advances in the diagnosis and treatment of advanced-stage gastric cancer, and discusses therapeutic decision primarily from the perspective of surgeons.

The incidence of gastric cancer ranks fifth among malignant tumors worldwide, with the fourth highest mortality rate. A noteworthy characteristic of our country is the high prevalence of advanced-stage patients of approximately 40%. Advanced-stage gastric cancer carries an unfavorable prognosis with median survival of around one year. Diagnosis methods for advanced-stage gastric cancer (such as laparoscopic exploration, molecular profiling, and artificial intelligence) are still being continuously improved, while chemotherapy remains the primary treatment. With the rapid development of medical science, the role of surgical intervention in advanced-stage gastric cancer is becoming increasingly prominent. Therefore, as gastric tumor surgeons, we should consider how to use a combination of treatments, including surgery, chemotherapy, targeted therapy, immunotherapy, and interventional therapy, based on different pathological stages and the heterogeneity of tumors. With a multidisciplinary approach involving experts from various fields, we can collectively improve the survival rate and quality of life for advanced-stage patients. This article provides a brief overview of the current advances in the diagnosis and treatment of advanced-stage gastric cancer, and discusses therapeutic decision primarily from the perspective of surgeons.

Objective:To explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis of pathogens in primary infectious diseases of the spine (IDS) and to reveal its pathogen spectrum.Methods:This is a retrospective multi-center case series study. Clinical data of 380 patients with primary IDS who were treated at four medical centers in China from December 2019 to April 2024 were retrospectively analyzed. Among them, 82 cases were from the Department of Spine Surgery at the Affiliated Hospital of Qingdao University, 129 cases were from the Orthopedics Section Ⅱ (Bone Infection), Public Health Clinical Center Affiliated to Shandong University, 112 cases were from the Department of Spine Surgery, Fuzhou Second General Hospital, and 57 cases were from the Department of Orthopedic Surgery, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. There were 238 males and 242 females, with an age of (61.4±13.1) years (range: 10 to 91 years). Specimens from the site of spinal infection were obtained for pathogen culture, pathological examination, and mNGS detection preoperatively or intraoperatively in all patients. The number, types, and positive rates of pathogens detected by the two methods were analyzed and compared using the Chi-square test.Results:Among the 380 patients, 320 had confirmed pathogenic bacteria, with the highest proportion being pyogenic bacterial infections, accounting for 76.9% (246/320). The most common pathogen was Staphylococcus aureus, accounting for 22.8% (73/320). Brucella accounted for 13.8% (44/320); Mycobacterium tuberculosis accounted for 6.3% (20/320). Fungal infections accounted for 3.4% (11/320), mainly Aspergillus and Candida. In addition, Mycoplasma was detected in 3 cases (0.9%) and Benacox body in 4 cases (1.2%). The pathogen spectrum constructed by mNGS covered 46 types of pathogens, higher than the 22 types detected by traditional methods. The positive rate of mNGS was 80.8% (308/381), significantly higher than the 27.9% (106/381) of traditional methods ( χ2=182.53, P<0.01). Conclusions:mNGS improves the positive rate of pathogen diagnosis in IDS, detecting a broader spectrum of pathogens, and serves as a valuable complement to traditional diagnostic methods. Combining both methods in the diagnosis of IDS can maximize detection rates, providing robust evidence for precise anti-infective treatment.