BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

Myeloid-derived cells (MDCs) are crucial in immune response and tissue homeostasis. They have high functional plasticity and can be polarized according to microenvironment signals. These cells, including macrophages, neutrophils, and dendritic cells (DCs), exhibit different functional polarization states in different pathological environments and are involved in the occurrence and development of diseases such as inflammation and tumors. Studies have shown that metabolic reprogramming plays a key role in the functional polarization of MDCs, affecting the cellular energy supply and regulating immune function. This paper reviews classification, function and polarization mechanism of MDCs and discusses metabolic reprogramming. In addition, the therapeutic strategies targeting MDC are summarized, which is expected to provide new targets for tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/metabolism* ; Neoplasms/pathology* ; Animals ; Immunotherapy/methods* ; Dendritic Cells/immunology* ; Macrophages/immunology*

Objective: To establish anin vitromodel of ferroptosis induced by Erastin and RAS-selective lethal 3(RSL3) in hepatoma cells, and to provide theoretical basis for the development of novel therapeutic strategies for HCC. Methods: Hepatoma cells(HCCLM3, HepG2, Hep3B, Huh7 and PLC/PRF/5) in logarithmic growth phase were treated with Erastin(0-40 μmol/L) and RSL3(0-10 μmol/L) at double concentrations respectively. After 24 h, CCK-8 method was used to detect cell viability, draw growth curve, calculate IC50, and HCC cells sensitive to inducers were selected for follow-up experiments. The effect of inducer on the state of hepatoma cells was observed under light microscope, and immunoblotting and flow cytometry were used to verify whether the ferroptotic modelin vitrowas successfully constructed. Results: Huh7, Hep3B and HepG2 cells were sensitive to Erastin and RSL3, but HCCLM3 and PLC/PRF/5 were insensitive to Erastin and RSL3. When the concentration of Erastin and RSL3 reached the maximum, the survival rate was still above 65%. Huh7, Hep3B and HepG2 cells were selected for subsequent experiments. Compared with the control group, the expression of Glutathione peroxidase 4(GPX4), a ferroptotic marker, was down-regulated in a concentration-dependent manner. In Huh7, Hep3B and HepG2 cells, lipid reactive oxygen species(ROS) levels significantly increased after 24 h treatment with 10 μmol/L and 20 μmol/L Erastin, respectively; in Huh7 cells, lipid ROS levels significantly increased after 24 h treatment with 0.5 μmol/L and 1 μmol/L RSL3, respectively; in Hep3B and HepG2 cells, lipid ROS levels significantly increased after 24 h treatment with 1 μmol/L and 2 μmol/L RSL3, respectively, compared with control group. Conclusion Huh7, Hep3B and HepG2 cells are highly sensitive to Erastin and RSL3. Huh7, Hep3B and HepG2 cells treated with 10 μmol/L Erastin for 24 h are good models for simulating ferroptosis induced by Erastinin vitro, Huh7 cells treated with 0.5 μmol/L RSL3 for 24 h and Hep3B and HepG2 cells treated with 1 μmol/L RSL3 for 24 h are good models for simulating ferroptosis induced by RSL3in vitro.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

Talent evaluation is an important part of the institutional mechanism for talent development. Based on the stakeholder theory, this study identified and defined the stakeholders in the evaluation of talents in public hospitals, and analyzed the needs of each party and their relationship with each other, and then built the evaluation path of talents in public hospitals. The stakeholders in the evaluation of talents in public hospitals included the government, society, hospitals and talents themselves. The strategic needs of talents of the government and the public welfare needs of talents of the society were transmitted to hospitals through policy orientation and functional positioning. Hospitals formed the evaluation implementation mechanism based on its own development needs through the establishment of talent evaluation index database and the setting of representative indexes of " field-oriented". Finally, the effectiveness of talent evaluation can be strengthened through the independent selection of the main evaluation categories and representative indicators by individual talents, as well as the personalized setting of relevant indicator weights by hospitals, in order to provide feedback on the evaluation needs of talents for the value of expertise. Constructing a talent evaluation system for public hospitals based on demand factors using a stakeholder theory analysis framework can provide reference for the reform of talent evaluation in public hospitals.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

【Objective】 To investigate the compatibility of human albumin and its internal packaging materials of Sinopharm Lanzhou Biopharmaceutical Co., Ltd. 【Methods】 One batch of inner packaging materials (medium borosilicate glass-molded injection bottle and halogenated butyl rubber plug for injection) was extracted with 4 extraction solvents to conduct the toxicological evaluation of potential inner packaging extracts. Through the simulated acceleration test, the trend analysis of the elements in the sample and the inner surface of the glass bottle were observed, and the routine drug inspection items during the long-term stability test process were determined. 【Results】 The detection results of the leaching elements of the internal packaging materials did not exceed the limit of 50%, and the organic matter safety threshold (margin of safety, MOS) was greater than 1.0, indicating that both the leaching elements and the organic matter had no safety risk to the user under the current exposure. The results of the simulated acceleration test show that the drug will not have the risk of peeling tablets after the long-term stability condition was placed for a period of time, and the routine inspection items of the long-term stability test drugs all meet the requirements of the pharmacopoeia. 【Conclusion】 The inner packaging material has no significant impact on the quality of drugs and has good overall compatibility, making it suitable for packaging human albumin.

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Frailty denotes a nonspecific clinical condition characterized by a decrease of physiological reservation in multiple systems, which makes individuals extremely vulnerable to stressors. Frailty increases the incidence of adverse outcomes and death of patients. However, frailty is reversible and preventable. Therefore, this article reviews theoretical models, assessment tools and influencing factors of frailty in elderly patients with hematologic maligilancy, so as to provide references for medical staff to carry out frailty management and related research in elderly patients with hematologic maligilancy.