OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

Research has confirmed that compared to traditional room temperature-stored platelets [RTP, (22±2) ℃], cold-stored platelets (CSP, 1-6℃) extend the stored time by inhibiting bacterial proliferation, representing an important strategy to break through the bottleneck of platelet storage. However, the low temperature environment induces significant changes in platelet morphology, metabolism and function. The morphological changes and surface marker changes together lead to functional impairment, which in turn affect its hemostatic efficacy. In recent years, research on metabolomics, apoptosis mechanisms, and innovative preservation strategies and technologies has provided new perspectives for intensive analysis of the damage mechanisms of CSP. This review summarizes the changes in CSP performance, active components, and damage mechanisms, explores the research progress in preservation solutions and methods, and combines them with the current clinical application status. The aim is to provide a theoretical basis for intensive analysis of CSP performance changes and optimization of platelet storage strategies, and promote the application of CSP based on its functional characteristics in emergency treatment of active bleeding patients in China.

Objective To investigate the current distribution of radiotherapy resources in Gansu Province, evaluate the equity of resource allocation, and provide a scientific basis for optimizing regional resource allocation. Methods A questionnaire survey was carried out to assess radiotherapy resources in medical institutions across Gansu Province, China. The equity of radiotherapy resource distribution and associated disparities were assessed using the Gini coefficient, Lorenz curve, and Theil index. Results A total of 23 medical institutions in Gansu Province provided radiotherapy services, comprising 39 radiotherapy devices and 438 professionals, of whom medical physicists accounted for 16.9%. The radiotherapy frequency was 0.47 cases per thousand population. The Gini coefficients for radiotherapy resource distribution ranged from 0.38 to 0.56 by population and from 0.52 to 0.70 by geography. The Theil index for radiotherapy resources ranged from 1.36 to 3.67. Conclusion Radiotherapy resources in Gansu Province were insufficient, and the capacity of radiotherapy service was suboptimal. The equity of radiotherapy resource allocation by geography was worse than that by population. Therefore, it is imperative to address the shortage of radiotherapy resources, strengthen the professional workforce, enhance the capacity radiotherapy service and resource utilization, optimize resource allocation, and promote regional equity in radiotherapy provision in Gansu Province.

BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

Malignant pleural effusion (MPE) refers to the accumulation of pleural fluid caused by metastasis from primary pleural malignancies or tumors originating elsewhere. It is associated with a poor prognosis. Current treatment strategies primarily include systemic anti-tumor therapy and local management of MPE based on the primary tumor. Numerous studies have documented diverse approaches for the local control of MPE. This review summarizes recent advances in local treatment strategies for primary tumor-related MPE, highlighting emerging pharmacological agents and innovative techniques.
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Humans ; Pleural Effusion, Malignant/drug therapy*

OBJECTIVES: Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS: SKF_525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF_525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC^® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS: The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R²=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.
Tandem Mass Spectrometry/methods* ; Humans ; Chromatography, High Pressure Liquid/methods* ; Substance Abuse Detection/methods* ; Liquid Chromatography-Mass Spectrometry