Therapeutic drug monitoring （TDM） is the core approach for individualized precision medication in clinical practice. Based on pharmacokinetics, it quantitatively measures in vivo drug concentrations using modern analytical techniques, mainly applied to drugs with a narrow therapeutic window, significant adverse reactions, and large interindividual pharmacokinetic variability across multiple categories. TDM plays an irreplaceable role in optimizing therapeutic regimens, reducing drug toxicity, and enhancing rational clinical drug use. TDM-applicable drugs were systematically reviewed in this paper, focusing on the working principles, clinical applications, advantages and limitations of mainstream analytical techniques （immunoassay, liquid chromatography tandem mass spectrometry，LC-MS/MS） and emerging ones （surface plasmon resonance and biolayer interferometry）, which provided a valuable reference for the standardized clinical application of TDM, rational selection of analytical methods, and subsequent technological research and development.

Spinal cord injury(SCI)is a central nervous system disease that can lead to motor,sensory,and autonomic dysfunction.Depending on the state of immune microenvironment,macrophage polarization can differentiate into M1/M2 phenotypes.The regulation of macrophage polarization by stem cells in many pathophysiological processes of SCI has become a hot topic of research in recent years.This review summarizes the relationship between macrophage polarization and SCI,and how mesenchymal stem cells(MSCs)and neural stem cells(NSCs)regulate macrophage polarization to improve SCI through paracrine secretion,delivery molecules,derived exosomes,and metabolic reprogramming pathways.It also summarizes the mechanism by which stem cells regulate the macrophage polarization phenotypes to promote SCI recovery through signaling pathways such as Janus tyrosine kinase/signal transducer and activator of transcription(JAK/STAT),Notch,Toll-like receptor 4/nuclear factor kappa-B(TLR4/NF-κB),phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt).The aim is to provide theoretical support for the treatment of SCI by regulating macrophage polarization with stem cells and to offer new perspectives for exploring the mechanism of stem cell therapy for SCI.

Atherosclerosis(AS)is an inflammatory cardiovascular disease characterized by plaque accumulation in the arterial wall,leading to increased morbidity and mortality of related cardiovascular disorders.The main pathological mechanisms of AS include lipid deposition,oxidative stress,and chronic inflammation,with disease progression involving endothelial cell dysfunction,macrophage polarization,foam cell formation,and smooth muscle cell proliferation or apoptosis.Mitochondria are essential organelles that provide energy for cellular metabolism,and the mitochondrial quality control(MQC)system is the fundamental mechanism maintaining mitochondrial functional homeostasis.MQC dysfunction can induce vascular phenotype changes through pathways such as oxidative stress,apoptosis,and inflammation,thereby promoting the progression of AS.Therefore,targeting MQC to regulate mitochondrial function may become a new direction for the treatment of AS.This review summarizes the molecular mechanisms of MQC,including mitochondrial biogenesis,mitochondrial dynamics,and mitochondrial autophagy(mitophagy),and further elucidates the role of abnormal MQC in the pathological processes of AS,aiming to provide a scientific basis for identifying potential targets to delay the progression of AS and developing related drugs.

Objective:To explore the predictive value of preoperative CT angiography (CTA) for incomplete endothelialization of the occluder after left atrial appendage closure (LAAC) in patients with atrial fibrillation.Methods:The clinical data of 92 atrial fibrillation patients underwent LAAC in the Tangdu Hospital of Air Force Military Medical University from January 2022 to June 2024 were retrospectively analyzed. CTA examinations were performed both before operation and 3 months after operation. Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening, diameter of anchoring area and effective depth were measured. After operation, the condition of occluder endothelialization was evaluated, and the patients were divided into the completely endothelialization group and the incomplete endothelialization group. Multivariate Logistic regression analysis was used to analyze the independent risk factors of occluder incomplete endothelialization after LAAC in patients with atrial fibrillation. The predictive value of independent risk factors was evaluated by the receiver operating characteristic (ROC) curve.Results:Among the 92 patients, CTA 3 months after the operation showed that 58 cases had complete occluder endothelialization (complete endothelialization group), and 34 cases had occluder incomplete endothelialization (incomplete endothelialization group). Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening and diameter of anchoring area in incomplete endothelialization group were significantly larger than those in complete endothelialization group: (28.35 ± 1.77) mm vs. (26.21 ± 2.21) mm, (22.09 ± 2.01) mm vs. (20.86 ± 1.75) mm, (512.76 ± 63.35) mm 2 vs. (453.83 ± 75.39) mm 2 and (24.71 ± 2.50) mm vs. (23.12 ± 2.40) mm, and there were statistical differences ( P<0.01); there was no statistical difference in effective depth between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the long diameter of left atrial appendage opening before operation was an independent risk factor for occluder incomplete endothelialization after LAAC in patients with atrial fibrillation ( OR = 2.141, 95% CI 1.217 to 3.768, P<0.01). ROC curve analysis result showed that the area under the curve of the long diameter of left atrial appendage opening before operation for predicting occluder incomplete endothelialization after LAAC in patients with atrial fibrillation was 0.768 (95% CI 0.674 to 0.862, P<0.01), the optimal cut-off value was 26.5 mm, the sensitivity was 88.2%, and the specificity was 55.2%. Conclusions:A larger long diameter of left atrial appendage opening before operation can lead to occluder incomplete endothelialization after LAAC in patients with atrial fibrillation.

Background and purpose:Tumor microangiogenesis is an important basis for tumor growth and metastasis,and its characteristics include angiogenesis,increased vascular permeability and abnormal capillary structure.Microangiogenesis not only affects the blood supply and metabolism of tumor,but also is directly related to the invasion,prognosis and treatment response of tumor.Dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)is a non-invasive imaging technique.By quantitatively analyzing the distribution and dynamic changes of contrast agents in tumor tissues,it can reflect the microvascular density(MVD),permeability and blood perfusion of tumors.The purpose of this study was to further clarify the application value of DCE-MRI in the diagnosis and treatment of rectal cancer by in-depth analysis of the relationship between quantitative analysis parameters of rectal cancer and microangiogenesis,and to promote the popularization and optimization of this technology in clinical practice.Methods:A total of 348 patients with rectal cancer who were scheduled for surgical treatment in Xinxiang Central Hospital from January 2021 to June 2024 were selected,and rectal cancer tissue specimens and adjacent tissues(＞5 cm away from tumor margin)were collected.This study was approved by the medical ethics committee of Xinxiang Central Hospital(approval number:2021-144-01K).The quantitative analysis parameters of DCE-MRI[Rate constant(Kep),volume transport constant(Ktrans),volume fraction of contrast agent in extracellular space(VE)]and MVD in cancer tissues and adjacent tissues were compared.The quantitative analysis parameters and MVD of DCE-MRI in rectal cancer patients with different differentiation degrees and clinical stages were compared.Spearman correlation was used to analyze the correlation between DCE-MRI parameters and differentiation degree,clinical stage and MVD in patients with rectal cancer.Results:The values of Kep value,Ktrans value,Ve value and MVD were higher in rectal cancer tissues than in adjacent tissues(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with low differentiated and middle differentiated rectal cancer were higher than those of patients with high differentiated rectal cancer(P＜0.05).The values of Kep value,Ktrans value,Ve value and MVD of patients with low differentiated rectal cancer were higher than those of patients with middle differentiated rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅱ,Ⅲ and Ⅳrectal cancer were higher than those of patients with stage Ⅰ rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅲ and Ⅳ rectal cancer were higher than those of patients with stage Ⅱ rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅳ rectal cancer were higher than those of patients with stage Ⅲ rectal cancer(P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were negatively correlated with the differentiation degree(r=-0.683,-0.743,-0.721,P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were positively correlated with clinical stage(r=0.764,0.703,0.814,P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were positively correlated with MVD(r=0.812,0.754,0.835,P＜0.05).Conclusion:DCE-MRI parameters are related to the differentiation degree,clinical stage and microangiogenesis of rectal cancer.

Background and purpose:Tumor microangiogenesis is an important basis for tumor growth and metastasis,and its characteristics include angiogenesis,increased vascular permeability and abnormal capillary structure.Microangiogenesis not only affects the blood supply and metabolism of tumor,but also is directly related to the invasion,prognosis and treatment response of tumor.Dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)is a non-invasive imaging technique.By quantitatively analyzing the distribution and dynamic changes of contrast agents in tumor tissues,it can reflect the microvascular density(MVD),permeability and blood perfusion of tumors.The purpose of this study was to further clarify the application value of DCE-MRI in the diagnosis and treatment of rectal cancer by in-depth analysis of the relationship between quantitative analysis parameters of rectal cancer and microangiogenesis,and to promote the popularization and optimization of this technology in clinical practice.Methods:A total of 348 patients with rectal cancer who were scheduled for surgical treatment in Xinxiang Central Hospital from January 2021 to June 2024 were selected,and rectal cancer tissue specimens and adjacent tissues(＞5 cm away from tumor margin)were collected.This study was approved by the medical ethics committee of Xinxiang Central Hospital(approval number:2021-144-01K).The quantitative analysis parameters of DCE-MRI[Rate constant(Kep),volume transport constant(Ktrans),volume fraction of contrast agent in extracellular space(VE)]and MVD in cancer tissues and adjacent tissues were compared.The quantitative analysis parameters and MVD of DCE-MRI in rectal cancer patients with different differentiation degrees and clinical stages were compared.Spearman correlation was used to analyze the correlation between DCE-MRI parameters and differentiation degree,clinical stage and MVD in patients with rectal cancer.Results:The values of Kep value,Ktrans value,Ve value and MVD were higher in rectal cancer tissues than in adjacent tissues(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with low differentiated and middle differentiated rectal cancer were higher than those of patients with high differentiated rectal cancer(P＜0.05).The values of Kep value,Ktrans value,Ve value and MVD of patients with low differentiated rectal cancer were higher than those of patients with middle differentiated rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅱ,Ⅲ and Ⅳrectal cancer were higher than those of patients with stage Ⅰ rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅲ and Ⅳ rectal cancer were higher than those of patients with stage Ⅱ rectal cancer(P＜0.05).The Kep value,Ktrans value,Ve value and MVD of patients with stage Ⅳ rectal cancer were higher than those of patients with stage Ⅲ rectal cancer(P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were negatively correlated with the differentiation degree(r=-0.683,-0.743,-0.721,P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were positively correlated with clinical stage(r=0.764,0.703,0.814,P＜0.05).The Kep value,Ktrans value and Ve value of rectal cancer patients were positively correlated with MVD(r=0.812,0.754,0.835,P＜0.05).Conclusion:DCE-MRI parameters are related to the differentiation degree,clinical stage and microangiogenesis of rectal cancer.

Objective:To explore the predictive value of preoperative CT angiography (CTA) for incomplete endothelialization of the occluder after left atrial appendage closure (LAAC) in patients with atrial fibrillation.Methods:The clinical data of 92 atrial fibrillation patients underwent LAAC in the Tangdu Hospital of Air Force Military Medical University from January 2022 to June 2024 were retrospectively analyzed. CTA examinations were performed both before operation and 3 months after operation. Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening, diameter of anchoring area and effective depth were measured. After operation, the condition of occluder endothelialization was evaluated, and the patients were divided into the completely endothelialization group and the incomplete endothelialization group. Multivariate Logistic regression analysis was used to analyze the independent risk factors of occluder incomplete endothelialization after LAAC in patients with atrial fibrillation. The predictive value of independent risk factors was evaluated by the receiver operating characteristic (ROC) curve.Results:Among the 92 patients, CTA 3 months after the operation showed that 58 cases had complete occluder endothelialization (complete endothelialization group), and 34 cases had occluder incomplete endothelialization (incomplete endothelialization group). Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening and diameter of anchoring area in incomplete endothelialization group were significantly larger than those in complete endothelialization group: (28.35 ± 1.77) mm vs. (26.21 ± 2.21) mm, (22.09 ± 2.01) mm vs. (20.86 ± 1.75) mm, (512.76 ± 63.35) mm 2 vs. (453.83 ± 75.39) mm 2 and (24.71 ± 2.50) mm vs. (23.12 ± 2.40) mm, and there were statistical differences ( P<0.01); there was no statistical difference in effective depth between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the long diameter of left atrial appendage opening before operation was an independent risk factor for occluder incomplete endothelialization after LAAC in patients with atrial fibrillation ( OR = 2.141, 95% CI 1.217 to 3.768, P<0.01). ROC curve analysis result showed that the area under the curve of the long diameter of left atrial appendage opening before operation for predicting occluder incomplete endothelialization after LAAC in patients with atrial fibrillation was 0.768 (95% CI 0.674 to 0.862, P<0.01), the optimal cut-off value was 26.5 mm, the sensitivity was 88.2%, and the specificity was 55.2%. Conclusions:A larger long diameter of left atrial appendage opening before operation can lead to occluder incomplete endothelialization after LAAC in patients with atrial fibrillation.

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

Objective:To explore the value of REG3α,sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:From January 2020 to March 2022,70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects,of which 50 cases were mild aGVHD(grade Ⅰ-Ⅱ)and 20 cases were severe aGVHD(grade Ⅲ-Ⅳ).30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group.Luminex platform was used to detect the protein expression levels of REG3α,sST2 and TNFR1 during aGVHD occurrence,and the differences between the three groups were analyzed by one-way ANOVA.According to the outcome of aGVHD treatment within 28 days,the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases.The ROC curve was used to analyze the value of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD.Results:The peripheral blood levels of REG3α,sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group(P＜0.05),and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group(P＜0.05).Compared with the good prognosis group,the peripheral blood levels of REG3α,sST2 and TNFR1 in the poor prognosis group were significantly higher(t=9.27,3.33,2.97;P＜0.01).ROC curve analysis showed that the area under the curve(AUC),sensitivity and specificity of the combined detection of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.Conclusion:The expression levels of REG3α,sST2 and TNFR1 were related to the severity of aGVHD.The combination of REG3α,sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD,which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.