BACKGROUND:Stress-induced damage to hippocampal neurons may underlie abnormalities in neuronal structure and function,ultimately leading to mood disorders.G protein-coupled receptors in brain tissue play an important role in mood regulation.OBJECTIVE:To analyze the mechanism of depression-like behavior in chronic social defeat stress mice based on high-throughput sequencing and bioinformatics analysis.METHODS:C57BL/6J mice were randomly divided into control group and model group.There was no special treatment in the control group,while a mouse model of chronic social defeat stress was established in the model group.Depression-like behavior was assessed through the sucrose preference test,tail suspension test,and forced swim test.Anxiety behavior was evaluated using the elevated plus-maze,while social behavior was measured through the social interaction test.Cognitive function was assessed with the Y-maze spontaneous alternation test.Immunofluorescence staining was performed to quantify microglia markers in the mouse hippocampus,and Nissl staining was used to examine neuronal damage in mice.High-throughput sequencing was used to identify differentially expressed genes and gene enrichment in the mouse hippocampus,and qPCR was used to measure the expression of G protein-coupled receptors in the mouse hippocampus.RESULTS AND CONCLUSION:(1)Compared with the control group,chronic social defeat stress mice showed significant behavioral impairments,including increased anxiety,depression,and cognitive deficits.(2)Additionally,the Nissl body light density in hippocampal neurons was significantly reduced in chronic social defeat stress mice.(3)Sequencing results revealed synaptic damage in the neurons after chronic social defeat stress.Microglia activation was also markedly increased in the hippocampus of CSDS mice.Furthermore,the expression of G protein-coupled receptors in the hippocampus was significantly higher in chronic social defeat stress mice compared with the control group.These findings suggest that chronic social defeat stress induces anxiety,depression,and cognitive deficits in mice,accompanied by neuropathological changes in the hippocampus,and that altered G protein-coupled receptors expression may play a key role in these behavioral and neuropathological changes.

Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

ObjectiveTo investigate the attitudes and competence of nursing interns toward hospice care， analyze the key factors influencing their performance， and provide targeted improvement suggestions to enhance their comprehensive quality. MethodsA total of 273 undergraduate nursing interns were investigated. General demographic data were collected， and the Chinese version of the Frommelt Attitude Toward Care of the Dying Scale， Form B （FATCOD-B） and the Hospice Care Competency Assessment Questionnaire were administered to evaluate their attitudes and competence in hospice care. A total of 270 valid questionnaires were recovered. Multiple linear regression was performed to analyze the influencing factors of hospice care attitudes and competence among nursing interns. ResultsThe total score of hospice care attitudes was （76.04±12.18） among these 270 nursing interns. Having cared for critically ill patients， receiving hospice care-related education， and experiencing the loss of relatives or friends in the past year were positive influencing factors for their hospice care attitudes， whereas avoidance of talking about death was a negative influencing factor. The total score of hospice care competence was （42.75±4.68）. Having cared for critically ill patients and receiving hospice care-related education represented positive influencing factors for their hospice care competence. ConclusionThe hospice care attitudes and competence of nursing interns are all at moderate levels. It is necessary to strengthen education and training on hospice care for nursing interns， improve the ability of nurses， and provide assistance for the development of hospice care.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

BACKGROUND:Stress-induced damage to hippocampal neurons may underlie abnormalities in neuronal structure and function,ultimately leading to mood disorders.G protein-coupled receptors in brain tissue play an important role in mood regulation.OBJECTIVE:To analyze the mechanism of depression-like behavior in chronic social defeat stress mice based on high-throughput sequencing and bioinformatics analysis.METHODS:C57BL/6J mice were randomly divided into control group and model group.There was no special treatment in the control group,while a mouse model of chronic social defeat stress was established in the model group.Depression-like behavior was assessed through the sucrose preference test,tail suspension test,and forced swim test.Anxiety behavior was evaluated using the elevated plus-maze,while social behavior was measured through the social interaction test.Cognitive function was assessed with the Y-maze spontaneous alternation test.Immunofluorescence staining was performed to quantify microglia markers in the mouse hippocampus,and Nissl staining was used to examine neuronal damage in mice.High-throughput sequencing was used to identify differentially expressed genes and gene enrichment in the mouse hippocampus,and qPCR was used to measure the expression of G protein-coupled receptors in the mouse hippocampus.RESULTS AND CONCLUSION:(1)Compared with the control group,chronic social defeat stress mice showed significant behavioral impairments,including increased anxiety,depression,and cognitive deficits.(2)Additionally,the Nissl body light density in hippocampal neurons was significantly reduced in chronic social defeat stress mice.(3)Sequencing results revealed synaptic damage in the neurons after chronic social defeat stress.Microglia activation was also markedly increased in the hippocampus of CSDS mice.Furthermore,the expression of G protein-coupled receptors in the hippocampus was significantly higher in chronic social defeat stress mice compared with the control group.These findings suggest that chronic social defeat stress induces anxiety,depression,and cognitive deficits in mice,accompanied by neuropathological changes in the hippocampus,and that altered G protein-coupled receptors expression may play a key role in these behavioral and neuropathological changes.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

OBJECTIVE To investigate the effects and potential mechanism of Panax notoginseng saponins （PNS） on gastric mucosal injury and inflammatory response in rats with chronic atrophic gastritis （CAG） via the stem cell factor（SCF）/cellular tyrosine kinase receptor（c-kit） signaling pathway. METHODS Male SD rats were used to establish a CAG rat model through intragastric administration of N -methyl- N ′-nitro- N -nitrosoguanidine combined with an irregular diet. Successfully modeled rats were randomly divided into a model group， positive control-vitacoenzyme group （Positive group， 250 mg/kg）， PNS low- and high-dose groups （PNS-L and PNS-H groups， 9， 18 mg/kg）， and high-dose PNS+SCF/c-kit inhibitor group （PNS-H+ISCK03 group， 18 mg/kg+47 mg/kg）， with 8 rats in each group. Additionally， 8 healthy rats were selected as a control group. After the final administration， the activities of serum gastrin （GAS）， motilin （MTL） and pancreatic polypeptide （PP）， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and IL-8 in gastric mucosal tissues， were measured in each group. Pathological changes of the gastric mucosal and ultrastructure of the epithelial cells were observed， and gastric mucosal atrophy was scored. Cell apoptosis in gastric mucosal tissues and the expressions of proliferating cell nuclear antigen （PCNA）， nuclear factor-κB p65 （NF-κB p65）， SCF and c-kit were detected. RESULTS Compared with the control group， the model group showed significantly increased inflammatory cell infiltration in the gastric mucosal， extensive epithelial cell detachment， severe ultrastructural damage， and significantly elevated or up-regulated gastric mucosal atrophy score， TNF-α and IL-8 levels in gastric mucosal， cell apoptosis rate， and NF-κB p65 protein expression. Meanwhile， serum levels of GAS and MTL， PP activity， the level of IL-10 in gastric mucosal tissue， and protein expressions of PCNA and SCF， as well as the phosphorylation level of c-kit， were significantly decreased or down-regulated （ P ＜0.05）. Compared with the model group， Positive， PNS-L and PNS-H groups exhibited markedly improved pathological changes in the gastric mucosal and significant amelioration of the quantitative indicators， with the PNS-H group showing significantly better improvement than the PNS-L group （ P ＜0.05）. However， ISCK03 significantly reversed the ameliorative effects of high-dose PNS on the above indicators in rats （ P ＜0.05）. CONCLUSIONS PNS improves gastric mucosal injury in CAG rats by reducing the inflammatory response and promoting gastric mucosal repair； these effects may be related to the activation of the SCF/c-kit signaling pathway.