ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

OBJECTIVE To construct an intelligent pharmaceutical Q&A platform for precision medication with low “artificial intelligence （AI） hallucination”， aiming to enhance the accuracy， consistency， and traceability of medication consultations. METHODS Medication package inserts were batch-processed and converted into structured data through Python programming to build a local pharmaceutical knowledge base. The retrieval and question-answering processes were designed based on large language models， and system integration and localized deployment were completed on Dify platform. By designing typical clinical medication questions and comparing the output of the intelligent pharmaceutical Q&A platform with the online version of DeepSeek across dimensions such as peak time retrieval， half-life， and dosage adjustment reasoning for patients with renal impairment， the accuracy and reliability of its retrieval and reasoning results were evaluated. RESULTS The intelligent pharmaceutical Q&A platform， constructed based on local drug package inserts， achieved 100% accuracy in retrieval and reasoning for peak time， half-life， and dosage adjustment schemes. In comparison， the online version of DeepSeek demonstrated accuracies of 30%（6/20）， 50%（10/20）， and 38%（23/60） across these three dimensions， respectively. CONCLUSIONS The constructed intelligent pharmaceutical Q&A platform is capable of accurately retrieving and extracting information from the local knowledge base based on clinical inquiries， thereby avoiding the occurrence of AI hallucinations and providing reliable medication decision support for healthcare professionals.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

ObjectiveTo investigate the expression of prefrontal cortical neurons， methyltransferase-like 3 （METTL3）， fat mass and obesity-associated gene （FTO）， and AlkB homolog 5 （ALKBH5） proteins in a mouse model of post-traumatic stress disorder （PTSD）. MethodsA PTSD mouse model was established using a single prolonged stress and foot shock stimulation （SPSS） method. The despair， anxiety， and learning and memory functions of PTSD mice were assessed through the open field test， Y-maze test， and forced swimming test. Neuronal damage was detected via HE and Nissl staining. The expression levels of METTL3， FTO， ALKBH5， and neuronal nuclear protein （NEUN） were assessed by Western blot and immunofluorescence staining. ResultsCompared to control group， PTSD mice subjected to SPSS exhibited signs of despair， anxiety， and impaired learning and memory. HE and Nissl staining results showed neuronal damage in the prefrontal cortex of PTSD mice. Western blot and immunofluorescence staining results showed that the expression of the m6A-related proteins METTL3 and FTO decreased， while the expression of ALKBH5 increased in the prefrontal cortex. Additionally， NEUN protein levels showed a declining trend. ConclusionThe pathogenesis of PTSD may be associated with neuronal damage in the prefrontal cortex and alterations in m6A methylation proteins.

Objective To evaluate the feasibility of intravesical instillation of urokinase and heparin sodium in the treatment of bladder clot irrigation.Methods This report discusses the diagnosis and treatment of three patients with bladder blood clot tamponade confirmed by abdominal and pelvic computed tomography(CT)scans enrolled from our hospital during Jun. to Sep. 2024, and discuss the relevant literature.Results A solution containing urokinase(20 000 IU)and heparin sodium(125 000 U)was instilled through a three-way catheter and retained for 30 minutes before drainage. Complete clot dissolution was achieved in all cases, with immediate relief of hypogastric distension and pain. Post-procedural CT showed restored bladder lumen patency. Hemoglobin levels decreased by 2-5 g/L without complications.Conclusion This preliminary trial demonstrated that intravesical instillation of urokinase-heparin provides a safe and effective minimally invasive alternative for bladder clot in irrigation cases.

BACKGROUND:In endodontics,revascularization and effective control of bacterial infection are prerequisite for regenerative repair of tissues and further development of the root apex.Ornidazole,carried in pulp-capping materials or vascularized scaffolding materials may control pulpal infections,but its effect on vascularization need to be investigated.OBJECTIVE:To investigate the residual concentration pattern of ornidazole in root canals and to evaluate the effects of ornidazole on endothelial cell proliferation,migration,and differentiation,as well as on vascular irritation.METHODS:(1)Ornidazole was encapsulated in the isolated pulp cavity and then immersed in Hank's balanced salt solution for 7 days.Ornidazole was then removed from the pulp cavity,reencapsulated in sterile water,and again immersed in Hank's balanced salt solution.The mass concentration of ornidazole in the pulp cavity fluid was measured periodically by colorimetric method.(2)Human umbilical vein endothelial cells were inoculated into well plates.Adherent cells were stimulated by the addition of lipopolysaccharide for 24 hours,and then co-cultured by the addition of 0,1,2,5,8,10 μg/mL ornidazole,to detect the cellular activity and migratory ability.Human umbilical vein endothelial cells were inoculated in well plates and co-cultured with different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole or stimulated by lipopolysaccharide for 24 hours followed by the addition of different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole.The gene expression of vascular endothelial growth factor and basic fibroblast growth factor as well as the protein expression of vascular endothelial growth factor was detected.(3)The chorioallantoic membrane assay was employed to assess the vascular irritation of 2 and 10 μg/mL ornidazole.RESULTS AND CONCLUSION:Residual ornidazole in exfoliated teeth was rapidly released within the initial 6 days,with a subsequent decrease in release rate,maintaining a concentration of approximately 2 μg/mL at the root apex after 8 days.Under lipopolysaccharide-induced inflammatory conditions,cell counting kit-8 and cell live-dead fluorescence staining showed that ornidazole(1-10 μg/mL)had no significant effect on the activity of human umbilical vein endothelial cells,and the cell scratch assay showed that ornidazole(1-10 μg/mL)had no obvious effect on the migratory ability of human umbilical vein endothelial cells.RT-qPCR assay showed that,after co-cultivation with ornidazole alone,the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells showed an overall decreasing trend.After co-culturing with ornidazole under lipopolysaccharide-induced inflammation,the mRNA expression of the two factors showed a rising trend in human umbilical vein endothelial cells.Western blot assay showed that vascular endothelial growth factor protein expression had an elevating trend in human umbilical vein endothelial cells after co-culture with ornidazole under lipopolysaccharide-induced inflammatory conditions.The chorioallantoic membrane assay showed that 2 and 10 μg/mL ornidazole were non-vascular irritating.To conclude,1-10 μg/mL ornidazole is non-cytotoxic and non-vascular irritating,promotes the expression of angiogenesis-related genes and proteins in inflammatory endothelial cells,and serves as a potential therapeutic agent for pulpal infection control.

Objective:To explore the application effect of family participatory multisensory support programme based on the theory of enriched environment on preterm infants and their mothers in neonatal intensive care unit (NICU).Methods:A historical comparative study was conducted. One hundred and sixteen pairs of preterm infants and their mothers admitted to NICU, Affiliated Hospital of Youjiang Medical University for Nationalities from March to October 2023 were selected by convenience sampling method and divided into control group and experimental group according to the time of admission. The control group was given routine care, while the experimental group implemented a family participatory multisensory support programme based on the enriched environment theory on the basis of the control group. The amplitude-integrated electroencephalography (aEEG) scores and the Chinese version of Parent-Child Interaction Feeding Scale (PCI-FS-C) scores before and after intervention, the Gesell developmental quotients at 40 weeks and 3 months of gestational age, the Chinese version of Maternal Attachment Inventory (CMAI) scores of preterm mothers on the day of discharge and 1 and 3 months after discharge were compared between the two groups.Results:A total of 105 pairs of premature infants and their mothers were included, 52 premature infants of control group, 29 males and 23 females; 53 premature infants of experimental group, including 32 males and 21 females. Before intervention, there were no significant differences in aEEG scores and PCI-FS-C scores between the two groups (all P>0.05). After intervention, the scores of aEEG and PCI-FS-C in the experimental group were (10.91 ± 2.18) and (12.62 ± 1.32) points, respectively, which were higher than (9.67 ± 1.94) and (10.42 ± 1.45) points in the control group, and the differences were statistically significant ( t=3.06, 8.15, both P<0.05). The Gesell developmental quotient were (54.03 ± 9.73), (55.17 ± 11.19), (57.20 ± 11.04), (53.60 ± 9.74), (55.17 ± 10.11) at 40 weeks of gestational age, and (77.15 ± 11.55), (76.62 ± 9.90), (72.76 ± 11.90), (81.47 ± 10.01), (76.51 ± 12.25) at 3 months of gestational age, respectively, which were higher than the control group (49.70 ± 9.07), (49.06 ± 8.61), (52.41 ± 9.01), (49.28 ± 8.78), (50.07 ± 12.52), and (71.10 ± 11.87), (69.02 ± 12.53), (65.77 ± 12.24), (75.08 ± 11.08), (68.63 ± 10.89), the differences were statistically significant ( t values were 2.30-3.49, all P<0.05). The CMAI scores of preterm mothers in the experimental group were (82.81 ± 12.85), (87.70 ± 10.29), (95.91 ± 8.76) points on the day of discharge and 1 and 3 months after discharge, respectively, which were higher than (68.71 ± 14.15), (82.04 ± 11.87), (90.98 ± 11.13) points of the control group, the differences were statistically significant ( t=5.35, 2.61, 2.52, all P<0.05). Conclusions:The family participatory multisensory support programme based on the theory of enriched environment can accelerate the maturation of brain electrical activity in preterm infants and promote brain function and neurobehavioural development; meanwhile, it improves maternal sensitivity and promotes the establishment of mother-infant attachment relationship in preterm infants.

Objective To assess the current status and influencing factors of high-risk populations for osteosarcopenia in elderly community residents,and to construct a health portrait for this group,revealing population characteristics and differences.Methods A convenience sampling method was employed to recruit 800 community-dwelling older adults in Hangzhou,China,between August and December 2024.Data were collected using the following validated instruments,namely the General Information Questionnaire,Age-adjusted Charlson Comorbidity Index,Chinese version of the Nutritional Form for the Elderly,Osteoporosis Self-Efficacy Scale,Social Frailty Screening Tool,Osteoporosis Risk One-Minute Test,and Osteoporosis Self-Assessment Tool for Asians.Additionally,objective physical measurements were obtained,including calf circumference,handgrip strength,and five-times sit-to-stand test time.The influencing factors were analyzed using univariate analysis and binary logistic regression,and two-step cluster analysis was employed for clustering to construct group profiles.Results 770 valid questionnaires were collected.The detection rate of high-risk osteosarcopenia in the elderly community is 27.53％.Older age,low BMI,prolonged sitting,chronic pain,low intake of soy products,low osteoporosis self-efficacy,and high social frailty are associated with a higher risk of osteosarcopenia.Totally 3 population portraits were constructed through clustering,including health-maintenance type,risk-ignoring type,and active management type.Conclusion The detection rate of high-risk elderly individuals with osteosarcopenia in communities is relatively high,with significant differences across groups.Intervention strategies can be proposed based on different group characteristics,providing a reference for precise interventions.

Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.