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.

ObjectiveTo evaluate the quality of Lygodium japonicum (Thunb.) Sw. (L. japonicum, Hai Jin Sha) by comparing its components without stewed (W) and stewed (S) using ultra-high-performance liquid chromatography (UHPLC) and chemometric analysis. Additionally, network pharmacology was employed to investigate the possible mechanisms of action of L. japonicum in the urinary calculi (UC) treatment.MethodsA fingerprinting method was established to identify components through UHPLC-tandem mass spectrometry. Chemometric techniques were used to compare the L. japonicum extraction methods. Furthermore, various network pharmacological approaches were used to identify and analyze the potential targets of the identified components in relation to UC.ResultsThe W and S extracts were distributed into two distinct clusters. Significant differences in the levels of protocatechuic aldehyde, caffeic acid, and p-coumaric acid were observed between S and W. Network pharmacology analysis revealed that the primary targets of L. japonicum in the UC treatment were serum albumin and epidermal growth factor receptors, with potential active components including protocatechuic acid and caffeic acid.ConclusionThis study comprehensively examined the therapeutic components of L. japonicum before and after boiling, shedding light on its potential mechanisms of action in UC treatment. These findings offer valuable insights into the development and utilization of L. japonicum resources.

According the Good Clinical Practice(GCP)and programmatic requirements,we analyze the management characteristics and the costs of drugs for clinical trials in different specialties from the drug management;The characteristics of the management of drugs for different specialties was summarize and the differential factors that may affect the management cost was explored,so as to provide theoretical support for the research institutions to utilize the resources in a rational and efficient way.This article provides a guarantee for the drug management with the aim of enhancing the quality and efficiency of clinical trials.

Lung cancer represents as one of the most prevalent malignant tumors globally,necessitating the urgent identification of additional biomarkers to facilitate precise stratified treatment and elevate its survival rates.Previous studies have focused on the correlation between the histopathological characteristics,driver gene mutations,and progno-sis of non-small cell lung cancer(NSCLC),with the aim of predicting the potential molecular background,treatment efficacy,and possible clinical outcomes of patients from the morphological perspective.This article aims to briefly sum-marize the advancements in emerging histopathological indicators of NSCLC,and discuss their implications for guiding the prognosis of this disease.

Lung cancer represents as one of the most prevalent malignant tumors globally,necessitating the urgent identification of additional biomarkers to facilitate precise stratified treatment and elevate its survival rates.Previous studies have focused on the correlation between the histopathological characteristics,driver gene mutations,and progno-sis of non-small cell lung cancer(NSCLC),with the aim of predicting the potential molecular background,treatment efficacy,and possible clinical outcomes of patients from the morphological perspective.This article aims to briefly sum-marize the advancements in emerging histopathological indicators of NSCLC,and discuss their implications for guiding the prognosis of this disease.

Objective This study aims to discuss and summarize the management system for drugs used in clinical trials,with the objective of elevating the management standards.Methods Considering the situation of diverse departmental needs and the multi-campus structure,the study analyzed and explored the management of drugs for clinical trials to build a corresponding management system,including pharmacy construction,equipment,personnel qualifications,data management,drug reception,storage,distribution,and recycling protocols.The effecttivness of the system was evaluated through comparative analysis of data from 2022 to 2023 at our hospital.Result Improvements in the management of drugs for clinical trials were observed in 2023 across varous aspects.Conclusion Refining the management system of drugs for clinical trials can enhance Good Clinical Practice(GCP)supervision and service,providing an important reference for the management system.

According the Good Clinical Practice(GCP)and programmatic requirements,we analyze the management characteristics and the costs of drugs for clinical trials in different specialties from the drug management;The characteristics of the management of drugs for different specialties was summarize and the differential factors that may affect the management cost was explored,so as to provide theoretical support for the research institutions to utilize the resources in a rational and efficient way.This article provides a guarantee for the drug management with the aim of enhancing the quality and efficiency of clinical trials.

Objective This study aims to discuss and summarize the management system for drugs used in clinical trials,with the objective of elevating the management standards.Methods Considering the situation of diverse departmental needs and the multi-campus structure,the study analyzed and explored the management of drugs for clinical trials to build a corresponding management system,including pharmacy construction,equipment,personnel qualifications,data management,drug reception,storage,distribution,and recycling protocols.The effecttivness of the system was evaluated through comparative analysis of data from 2022 to 2023 at our hospital.Result Improvements in the management of drugs for clinical trials were observed in 2023 across varous aspects.Conclusion Refining the management system of drugs for clinical trials can enhance Good Clinical Practice(GCP)supervision and service,providing an important reference for the management system.

Objective To observe the correlations of quantitative parameters of contrast-enhanced ultrasound(CEUS),micro-flow imaging(MFI)and shear wave elastography(SWE)with tumor microenvironment(TME)acidification in nude mice MCF7 breast cancer.Methods MCF7 human breast cancer cells were injected subcutaneously into 20 BALB/c-nu nude mice,and modeling was regarded as successful when tumor grew to 150-200 mm3.Then,CEUS,MFI and SWE were performed to obtain relevant parameters,including time-intensity curve(TIC)parameters(peak intensity[PI],area under the curve[AUC]),vessel index(VI)and maximum,median and mean Youngs modulus(Emax,Emed,Emean).Tumor pH value was measured using fluorescence quenching method,and its correlation with CEUS,MFI and SWE parameters were analyzed.Results pH value of MCF7 breast cancer tissue in nude mice was 6.05-6.43,with an average of 6.27±0.05,which in high perfusion area was significantly higher than in low perfusion area(P＜0.001).PI and AUC of TIC and VI were all positively correlated with pH value(r=0.661,0.611,0.768,all P＜0.001),while Emax,Emed and Emean were negatively correlated with pH value(r=-0.490,-0.562,-0.571,all P＜0.001).Conclusion TIC parameters and VI of MCF7 breast cancer in nude mice were positively correlated with TME acidification,while Emax,Emed and Emean were negatively correlated with TME acidification.

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated-(p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4.IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.