Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVE To prepare patchouli oil enteric-coated dropping pills, evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC). METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters. Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids. Finally, colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1; and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9 ℃, and dropping pills at the speed of 33 drops·min−1, with dropping distance set at 6 cm; the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid. Compared with free patchouli oil, patchouli oil enteric-coated dropping pills significantly alleviated the pathological symptoms such as weight loss, hematochezia and colon shortening in rats; the expression of pro-inflammatory cytokines IL-6, IL-1β, and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated. The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α was significantly down-regulated. CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

Objective To investigate the proliferation inhibition effect induced by medicarpin in liver cancer cells and its mechanism.Methods HepG2,HCC-M,and Hep3B cell lines were used to investigate the impact of medicarpin on the proliferation and survival of liver cancer cells.Changes(50 μmol/L medicarpin)in cell morphology were observed by inverted microscope and the proliferative capacity of cells(12.5,25,50 μmol/L medicarpin)was assessed using colony formation assays.To explore the potential mechanisms of medicarpin,the Swiss Target Prediction database was used to predict its target proteins.Subsequently,protein-protein interaction networks were constructed using STRING and Cytoscape,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Flow cytometry assay was used to evaluate cell cycle progression,while Western blotting was performed to assess the expression levels of cell cycle-related proteins.Furthermore,the effects of medicarpin on different cell lines with various levels of p53 expression were compared to validate the role of p53 in medicarpin-induced cell cycle arrest in liver cancer cells.Results Morphological changes such as disrupted membrane integrity,nuclear shrinkage,and loss of intercellular connections were observed in liver cancer cells treated with medicarpin.Additionally,a significant decrease in cell numbers was evident at various concentrations(12.5,25,50 μmol/L),and colony formation assays indicated that medicarpin significantly inhibited the quantity of colonies formed by liver cancer cells(P<0.05).The network construction and functional enrichment analysis indicated that medicarpin targets are enriched in cell cycle regulatory signaling pathways.Flow cytometry result showed that medicarpin induced G2/M cell cycle arrest in HepG2 cells,accompanied by the accumulation of p53 protein and downregulation of the cell cycle regulator cdc2(P<0.05).However,the G2/M phase cell cycle arrest induced by medicarpin could be reversed by a p53 inhibitor.More importantly,medicarpin was unable to induce G2/M phase cell cycle arrest in Hep3B(p53-null)and p53 knockout HCT116 cells,consistently indicating the critical role of p53 in medicarpin-induced G2/M phase cell cycle arrest.Conclusion Medicarpin inhibits the proliferation of liver cancer cells,and its anticancer effect is related to p53-dependent G2/M cell cycle arrest.

Objective To investigate the proliferation inhibition effect induced by medicarpin in liver cancer cells and its mechanism.Methods HepG2,HCC-M,and Hep3B cell lines were used to investigate the impact of medicarpin on the proliferation and survival of liver cancer cells.Changes(50 μmol/L medicarpin)in cell morphology were observed by inverted microscope and the proliferative capacity of cells(12.5,25,50 μmol/L medicarpin)was assessed using colony formation assays.To explore the potential mechanisms of medicarpin,the Swiss Target Prediction database was used to predict its target proteins.Subsequently,protein-protein interaction networks were constructed using STRING and Cytoscape,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Flow cytometry assay was used to evaluate cell cycle progression,while Western blotting was performed to assess the expression levels of cell cycle-related proteins.Furthermore,the effects of medicarpin on different cell lines with various levels of p53 expression were compared to validate the role of p53 in medicarpin-induced cell cycle arrest in liver cancer cells.Results Morphological changes such as disrupted membrane integrity,nuclear shrinkage,and loss of intercellular connections were observed in liver cancer cells treated with medicarpin.Additionally,a significant decrease in cell numbers was evident at various concentrations(12.5,25,50 μmol/L),and colony formation assays indicated that medicarpin significantly inhibited the quantity of colonies formed by liver cancer cells(P<0.05).The network construction and functional enrichment analysis indicated that medicarpin targets are enriched in cell cycle regulatory signaling pathways.Flow cytometry result showed that medicarpin induced G2/M cell cycle arrest in HepG2 cells,accompanied by the accumulation of p53 protein and downregulation of the cell cycle regulator cdc2(P<0.05).However,the G2/M phase cell cycle arrest induced by medicarpin could be reversed by a p53 inhibitor.More importantly,medicarpin was unable to induce G2/M phase cell cycle arrest in Hep3B(p53-null)and p53 knockout HCT116 cells,consistently indicating the critical role of p53 in medicarpin-induced G2/M phase cell cycle arrest.Conclusion Medicarpin inhibits the proliferation of liver cancer cells,and its anticancer effect is related to p53-dependent G2/M cell cycle arrest.

Under the background of performance evaluation in nationwide tertiary public hospitals and the DRGs reform, how to improve the efficiency of daytime surgery management is becoming a hotspot for hospital managers. Since July 2020, a tertiary general hospital applied the theory of incentive compatibility to guide the medical workers to consciously strive to achieve such management goals as improving the quantity and quality of daytime surgeries by constructing an organizational management system, increasing performance rewards for daytime surgical teams, rewarding advanced collectives and individuals, convening work coordination and promotion meetings, formulating penalty terms, and strengthening supervision of surgical quality and safety indicators. The implementation rate of daytime surgery in hospitals, the number of departments conducting daytime surgery, the number of covered diseases, and the satisfaction rate of inpatients had increased from 6.94%, 6 departments, 64 diseases, and 90.5% in 2019 to 24.08%, 21 departments, 125 diseases, and 95.0% in 2022, respectively. The incidence of daytime surgical bleeding, and readmissions within 15 days decreased from 0.6% and 0.5% in 2019 to 0.5% and 0.2% in 2022, respectively. The theory of incentive compatibility was in line with the development goals of daytime surgery in China, providing an optimal strategy for improving the management efficiency of daytime surgery according to local conditions.

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

Objective: To construct Bayes discriminant function for clinical classification of common and severe Japanese encephalitis (JE) cases, and to identify cases accurately with quantitative indicators. Methods: Samples of confirmed common and severe JE cases reported by the epidemic surveillance system of Gansu Provincial Center for Disease Control and Prevention from 2005 to 2017 were collected. Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis were used to screen meaningful clinical indicators, so as to construct and evaluate Bayes discriminant function. Results: There were 256 common JE cases and 257 severe JE cases. There were no significant differences in sex, age and occupation distributions between the two groups (P>0.05) and there was significant difference in case fatality rate (P<0.05). Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis, combined with using related literature, to screen 11 clinical indicators for the construction of Bayes discriminant function. Interactive validation showed that the sensitivity of discriminant function was 71.48% (95%CI: 65.53%-76.93%) and the specificity was 73.93% (95%CI: 68.11%-79.19%). The area under ROC curve was 0.761 (95%CI: 0.720-0.803) and the total accuracy rate was 72.71%. Conclusion Bayes discriminant function can be used to identify common and severe JE cases more accurately, which is helpful for the reasonable treatment and good prognosis of JE patients.

Objective:To determine clinical curative effects of ozone therapy for pemphigus vulgaris.Methods:Ozone hydrotherapy was used as an aid treatment for 32 patients with pemphigus vulgaris.The hydropathic compression of potassium permanganate solution for 34 patients with pemphigus vulgaris served as a control.The main treatment for both groups were glucocorticoids and immune inhibitors.The lesions of patients,bacterial infection,usage of antibiotics,patient's satisfaction,and clinical curative effect were evaluated in the 2 groups.Results:There was no significant difference in the curative effect and the average length of staying at hospital between the 2 groups (P＞0.05).But rate for the usage of antibiotics was significantly reduced in the group of ozone hydrotherapy (P=0.039).The patients were more satisfied in using ozone hydrotherapy than the potassium permanganate solution after 7-day therapy (P＞0.05).Conclusion:Ozone hydrotherapy is a safe and effective aid method for pemphigus vulgaris.It can reduce the usage of antibiotics.