Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

Objective:To establish the objective of zero inventory management of in vitro diagnostic reagents,to evaluate the quality of supply chain,and to improve the existing problems in the supply of reagents.Methods:The problems existing in the management of in vitro diagnostic reagents were analyzed from the aspects of inventory,supply efficiency and product quality,and the management system of hospital operation,management quality and patient benefit optimization was established,and the zero-inventory management path and quality evaluation model were constructed.85 models of 21 types of in vitro diagnostic reagents purchased by Jiangsu Subei People's Hospital from January 2020 to March 2023 were selected.According to different supply chain quality management methods,on-demand inventory management mode(referred to as mode 1)and zero inventory management mode(referred to as mode 2)were adopted respectively.The demand procurement,inventory management and clinical use effects of the two management modes were compared.Results:The reagent procurement demand compliance rate,supply capacity high-quality quality rate and clinical use matching rate of mode 2 were(93.35±3.62)%,(94.87±2.63)% and(96.08±2.31)%,respectively,which were higher than those of mode 1,the difference was statistically significant(Z=2.489,2.836,2.838,P<0.05).The number of cases of long-term overstocking of products,substandard environment and untimely information in mode 2 were(2.92±2.54)cases,(2.83±1.59)cases and(5.58±3.12)cases,respectively,which were lower than those in mode 1,the difference was statistically significant(Z=2.959,3.037,3.703,P<0.05).The satisfaction of clinical departments,medical technology departments and procurement center with the supply,distribution and information communication of in vitro diagnostic reagents in mode 2 were 97.8% and 93.3%,97.0% and 87.9%,100% and 84.6%,respectively,which were higher than those in mode 1,the difference was statistically significant(x2clinical departments=5.428,6.133,x2medical technology departments=3.958,3.937,x2procurement center=5.159,4.996,P<0.05).Conclusion:The zero inventory management model can improve the standardization of in vitro diagnostic reagent demand procurement,reduce the incidence of backlog failure in inventory management,and improve the quality of clinical supply services.

Purpose To investigate the clinical value of multi-center digital mammography radiomics nomogram model in predicting triple-negative breast cancer(TNBC).Materials and Methods The digital mammograms of 462 patients with pathologically confirmed breast cancer from November 2016 to March 2022 were retrospectively analyzed,including 243 cases from Yijishan Hospital of Wannan Medical College(institution 1),106 cases from Fuyang People's Hospital(institution 2)and 113 cases from Taihe People's Hospital(institution 3).According to the results of immunohistochemistry,a total of 349 breast cancer patients in institution 1 and institution 2 were randomly divided into the training group(244 cases,including 41 TNBC and 203 non-TNBC)and the validation group(105 cases,including 18 TNBC and 87 non-TNBC)according to the ratio of 7∶3,113 breast cancer patients(24 TNBC and 89 non-TNBC)from institution 3 were included in the external validation group.Comparing the mediolateral oblique and cranial cauda digital mammography images,the mammography imaging with larger lesion areas were selected,and the image segmentation and radiomics feature extraction were performed.The radiomics model was constructed by using Logistic regression.The clinicopathological parameters and radiomics scores were used to construct a nomogram.Receiver operating characteristic and decision curve analysis were used to evaluate the model performance.To compare The predictive performance between the models was compared.Results Finally,four radiomics features closely related to TNBC were selected to construct an radiomics model.The area under the curve,sensitivity and specificity of TNBC predicted by the radiomics model in training group,validation group and external test group were 0.868,90.24%and 72.91%,0.827,72.22%and 75.86%,0.837,70.83%and 78.65%,respectively.The area under the curve,sensitivity and specificity of TNBC predicted by the combined model in the training group,validation group and external test group were 0.903,80.49%and 86.70%,0.890,77.78%and 88.51%,0.870,62.50%and 85.39%,respectively.The combined model was better than the single image omics model in predicting TNBC,and the difference was statistically significant between the training group and the verification group(Z=2.061,2.064,both P<0.05),but not between the external test group(Z=1.223,P=0.221).In three group,decision curve analysis showed that the nomogram predicted a higher net benefit than the radiomics model for triple-negative breast cancer.Conclusion The radiomics model has high diagnostic efficiency in predicting TNBC,and the nomogram model combined with the radiomics score and histological grading can further improve the prediction efficiency.

Positive pressure bio-protective equipment is a key protective equipment for high-level biosafety laboratories, which provides comprehensive protection for professionals working in pathogenic microorganisms or other biological contamination environments. This paper summarizes the development status of positive pressure bio-protective equipment at home and abroad, analyzes the existing problems of the current positive pressure bio-protective equipment, and puts forward suggestions, to provide reference for the development and application of positive pressure bio-protective equipment in our country.

Objective:To explore the behavioral intentions of pediatric nurses towards using vascular visualization devices in light of the theory of planned behavior.Methods:This was a qualitative study. From March to November 2023, 20 pediatric nurses from Peking University First Hospital were selected using purposive sampling for semi-structured interviews. The interview data were analyzed and themes were extracted using Colaizzi 7-step analysis method.Results:The behavioral intentions of pediatric nurses towards the use of vascular visualization devices could be summarized into nine themes based on the theory of planned behavior. Attitudes towards behavior included positive evaluations, negative evaluations, and unclear information. Subjective norms involved peers' attitudes as well as expectations and pressures from patients. Perceived behavioral control encompassed workload, level of knowledge, more limited equipment performance, and external resource support.Conclusions:The behavioral intentions of pediatric nurses towards the use of vascular visualization devices are influenced by their attitudes towards the behavior, subjective norms, and perceived behavioral control. Nursing managers should conduct standardized training on vascular visualization devices to enhance nurses' knowledge and skills, while also valuing the sources of various supports to create a supportive environment for the use of vascular visualization devices. This will improve the usage experience of pediatric nurses and promote the use of vascular visualization devices in pediatric nursing practice.

Objective:To investigate effect of vitexin on macrophage polarization and its impact on tumor growth in a mouse model of prostate cancer.Methods:C57BL/6J male mice were used to establish RM-1 prostate cancer xenograft model.Mice were ran-domly divided into model group,vitexin-low,medium and high doses groups(40,80,160 mg/kg),and cisplatin group as positive control.After continuous administration for 16 days,mice were euthanized and tumor mass was measured.HE staining was performed to observe tumor morphology.Immunohistochemistry was used to detect Ki67 positive rate.Flow cytometry was conducted to measure expressions of CD86+CD11b and CD206+CD11b in tumor-associated macrophages.CCK8 assay was performed to assess cytotoxic effect of vitexin on RAW264.7 macrophages to determine suitable concentrations.RT-qPCR was used to measure mRNA expressions of M2 macrophage markers,including arginase-1(ARG-1),Fizz1 and Ym1.Results:Vitexin inhibited tumor volume and weight,induced tumor tissue necrosis,suppressed Ki67 protein expression,increased expression of CD86+CD11b+M1 macrophages,and inhibited CD206+CD11b+M2 macrophage expression in mouse tumor tissues in vivo.Vitexin at concentrations of 10～20 μmol/L showed no cyto-toxicity on RAW264.7 macrophages in vitro,and promoted expression of iNOS in IL-4-induced M2 macrophages while inhibiting CD206 expression,as well as suppressed mRNA expressions of ARG-1,Fizz1 and Ym1.Conclusion:Vitexin effectively inhibits tumor growth in a mouse model of prostate cancer,possibly by regulating M2 macrophages towards an M1 phenotype and exerting immunomodulatory effects.

The difference in the crystal form of the drug leads to different solubility and stability,affecting drug's the clinical efficacy and bioavailability.Therefore,in recent years,drug crystal forms have received more and more attention from researchers.By reviewing and sorting out relevant literature,this paper summarizes the research progress of drug crystallization theory in recent years from the aspects of influencing factors of drug crystal form,identification and control of drug crystal form,drug crystal form evaluation methods,and applications,aiming to provide a reference for drug crystal form control and process screening.

Traditional Chinese medicine monomer has certain curative effects in tumor treatment,but its low targeting and difficulty in gathering at the tumor site limit its application.As a new type of drug delivery method,environmentally responsive nano drug delivery system has the advantages of targeted drug delivery,reducing drug side effects,and environmentally responsive release,and has been widely used in tumor treatment.In this paper,by consulting and sorting out the relevant literature,the general situation of traditional Chinese medicine monomers in the treatment of tumors,the classification of environment-responsive traditional Chinese medicine monomer nano drug delivery system,and its application in tumor treatment are summarized in three aspects,to provide ideas for solving the limitations of traditional Chinese medicine monomer in the treatment of tumor.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells