Based on network pharmacology,molecular docking technology and experimental valida-tion to explore the therapeutic efficacy and mechanism of action of baicalin(BC)on kidney injury caused by Klebsiella pneumoniae(KP)infection.The inhibitory activity of BC against KP was de-termined by in vitro experiments;a mouse kidney injury model was established,and the therapeu-tic effect was preliminarily verified by ophthalmoscopy and pathological histology;three pro-in-flammatory factors,namely,TNF-α,IL-10,and IL-1β,were detected by ELISA;and the cyber-pharmacology technology was utilized by PubChem,TCMSP,STRING,Cytoscape,AutoDocks and other databases and software to construct the PPI network as well as to perform GO function and KEGG enrichment analyses;and molecular docking technology was used to assess the binding ac-tivity of the drugs to the core targets and to speculate on the signaling pathways of the drug action.The results showed that BC had a better inhibitory effect on KP in the in vitro experiments;path-ological histology showed a significant therapeutic effect of BC;compared with the infected group,the content of pro-inflammatory factors TNF-α,IL-10,and IL-1β in the baicalin treatment group were significantly decreased(P≤0.05).Twenty-four core targets and 11 pathways of action were screened by network pharmacology,and BC docked stably with the acquired core targets TP53,PTGS2,MAPK1,MAPK8,TNF,BCL2,and IGF1 molecules,and it was speculated that BC might exert its antibacterial and anti-inflammatory effects through the signaling pathways of PI3K-Akt,MAPK,HIF-1,and NF-kappa B,etc.This study lays the foundation for further research on the mechanism of action of baicalin on renal injury.

Based on network pharmacology,molecular docking technology and experimental valida-tion to explore the therapeutic efficacy and mechanism of action of baicalin(BC)on kidney injury caused by Klebsiella pneumoniae(KP)infection.The inhibitory activity of BC against KP was de-termined by in vitro experiments;a mouse kidney injury model was established,and the therapeu-tic effect was preliminarily verified by ophthalmoscopy and pathological histology;three pro-in-flammatory factors,namely,TNF-α,IL-10,and IL-1β,were detected by ELISA;and the cyber-pharmacology technology was utilized by PubChem,TCMSP,STRING,Cytoscape,AutoDocks and other databases and software to construct the PPI network as well as to perform GO function and KEGG enrichment analyses;and molecular docking technology was used to assess the binding ac-tivity of the drugs to the core targets and to speculate on the signaling pathways of the drug action.The results showed that BC had a better inhibitory effect on KP in the in vitro experiments;path-ological histology showed a significant therapeutic effect of BC;compared with the infected group,the content of pro-inflammatory factors TNF-α,IL-10,and IL-1β in the baicalin treatment group were significantly decreased(P≤0.05).Twenty-four core targets and 11 pathways of action were screened by network pharmacology,and BC docked stably with the acquired core targets TP53,PTGS2,MAPK1,MAPK8,TNF,BCL2,and IGF1 molecules,and it was speculated that BC might exert its antibacterial and anti-inflammatory effects through the signaling pathways of PI3K-Akt,MAPK,HIF-1,and NF-kappa B,etc.This study lays the foundation for further research on the mechanism of action of baicalin on renal injury.

BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

Objective To analyze the occurrence characteristics of adverse events following immunization (AEFI) of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in Hebei Province and to evaluate the safety of the vaccine. Methods AEFI cases related to vaccination of PPSV-23 in Hebei Province from January 1, 2020 to December 31, 2022 were collected through the AEFI surveillance module of Chinese Center for Disease Control and Prevention Information System. The incidence of reported AEFI cases were then analyzed and compared. Results The reported incidence rate of AEFI of PPSV-23 was 56.12 /100,000 doses, and the incidence rate of adverse reactions was 55.50 /100 000 doses. The incidence rate of common adverse reactions was 53.94/100 000 doses, and the incidence rate of rare adverse reactions was 1.56/100 000 doses. Most of the reported AEFI cases caused by PPSV-23 were common adverse reactions, which occurred mainly within one day after vaccination, and the overall regression was positive. Conclusion The 23-valent pneumococcal polysaccharide vaccine used in Hebei Province is safe，but its safety monitoring still needs to be strengthened.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

Most solid tumors suffer from inadequate blood perfusion and oxygenation, leading to a hypoxic microenvironment that accelerates tumor progression and adversely impacts prognosis. Thus, improving oxygenation in tumor tissues is crucial for enhancing the sensitivity and efficacy of tumor therapy. Hemoglobin-based oxygen carriers (HBOCs), as a type of oxygen-carrying nanoparticles, can not only carry and release oxygen but also reach the small blood vessels of obstructive microcirculation to deliver oxygen for anoxic tissues and organs, which are difficult for normal red blood cells to pass through. Studies have demonstrated that the application of HBOCs as a potential nanoscale efficient oxygen carrier in tumor therapy can enhance tissue oxygenation and hold great promise for applications in tumor therapy.This review summarizes the impact of hypoxia in tumors and highlights the progress and potential mechanisms of using HBOCs in tumor radiotherapy, chemotherapy, new kinetic therapy and immunotherapy.

【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) in chemoimmunotherapy for breast cancer in mice. 【Methods】 A 4T1 breast cancer in situ tumor model was established, and 15 mice were randomly divided into 3 groups: blank group: no intervention; Control group: doxorubicin + PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg^-1 once a week and PD-1 inhibitor 12.5 mg·kg^-1 once a week; Experimental group: DOX+ a-PD-1+ PolyCHb, the usage of DOX and a-PD-1 was the same as above, PolyCHb: PolyCHb 600 mg·kg^-1 was injected into the tail vein, three times a week; The administration period was 4 weeks. During the administration, the tumor volume was recorded 3 times per week, the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated. The mice were killed on the 29th day, and the tumor was removed and weighed to calculate the tumor inhibition rate. Immunofluorescence, HE staining, TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α, observe the pathological changes of tumor tissue, detect the apoptosis of tumor cells, and detect the expression of tumor proliferation index Ki67. 【Results】 Compared with the blank group and the control group, the tumor volume in the experimental group decreased significantly (P<0.05) and the tumor inhibition rate (%) increased significantly (P<0.05). The content of HIF-1α in tumor tissue in experimental group decreased (P<0.05). In the experimental group, the growth area of tumor tissue decreased, accompanied by the increase of necrosis area; The positive rates (%) of apoptosis in tumor tissues of blank group, control group and experimental group were 18.79±0.62, 20.68±1.19 and 41.65±2.99 respectively (F=135.2, P<0.001). In addition, the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group (P<0.05). 【Conclusion】 PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model, and the mechanism may be related to the decrease of HIF-1α expression, the promotion of apoptosis and the inhibition of cell proliferation.

【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL^-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL^-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

【Objective】 To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. 【Methods】 CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. 【Results】 When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P<0.01). The results of H&E staining showed that the PL MNs group had fewer inflammatory cell infiltrates and bleeding spots. The number of fibroblasts and new microvascular in the control group was worse than that in the PL MNs group and the PL smear group. The results of immunohistochemistry indicated that the expression of pro-inflammatory factor IL-6 decreased, while anti-inflammatory factor TGF-β and angiogenesis index CD31 increased in the PL MNs group, which were significantly different from those in the other three groups (P<0.01). 【Conclusion】 The PL MNs prepared in this experiment have good mechanical properties, which has a positive effect on the wound healing of diabetic mice, and provides a new idea for diabetic wound healing.