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*

Objective:To prepare novel dental composite resins using zinc(Zn)-and nitrogen(N)-modified titanium dioxide(TiO?)nanoparticles(NPs)and mesoporous alumina(Al?O?,r type,20 mm)NPs as reinforcing fillers,systematically evaluating their antibacterial activity,mechanical strength,basic performance,and biosafety to obtain the dental composite resins with excellent antibacterial activity and mechanical strength.Methods:Zn-N-TiO? NPs and mesoporous Al?O? NPs were added into a resin matrix at varying mass ratios to prepare five composite resins:control group(no filler),group 0(Zn-N-TiO?∶Al?O?=1∶0),group 1(Zn-N-TiO?∶Al?O?=1∶1),group 2(Zn-N-TiO?∶Al?O?=1∶2),and group 3(Zn-N-TiO?∶Al?O?=1∶3).Plate colony counting method was used to detect the number of adhered bacteria on composite resin surfaces in various groups and calculate the antibacterial rate;scanning electron microscope(SEM)was used to observe the morphology of adhered bacteria in various groups;universal testing machine was used to measure flexural strength(FS)and elastic modulus(EM)of composite resins in various groups;SEM was used to observe fracture surface morphology of composite resins in various groups;microhardness tester was used to determine Vickers microhardness of the composite resins in various groups;Fourier transform infrared spectroscope was used to detect double bond conversion rate(DC)after 20 s photocuring and calculate curing depth;water contact angle meter was used to measure water contact angle(WCA),water sorption property(WSP),and water solubility level(WSL)of composite resins in various groups;cell counting kit-8(CCK-8)method was used to evaluate relative growth rate(RGR)of the mouse fibroblast L-929 cells cultured in composite resin extracts on days 1,3,and 5 and determine in vitro cytotoxicity grade.Results:The plate colony counting results showed that compared with control group,the colony counts on agar plates in the other groups were significantly reduced,with group 1 showing the lowest count.The SEM images results showed densely distributed and morphologically intact Streptococcus mutans in control group;small clusters of bacteria with depressed cell membranes in group 0 and group 3;sparsely distributed bacteria with obvious membrane shrinkage and cytoplasmic leakage in group 1 and group 2.No statistically significant difference in colony counts was found between group 1 and group 2(P>0.05),but both were lower than the other groups(P<0.05).All the composite resins in experimental groups exhibited>85%antibacterial rates,with group 1 and group 2 exceeding 99%.The composite resins in group 0 showed the lowest FS.With addition of mesoporous Al?O?,the FS of the composite resin in group 1 and group 2 were significantly increased,with the composite resin in group 2 showing the highest FS among all groups.Although the FS of the composite resin in group 3 was lower than that in group 2,but it remained higher than other groups(P<0.05).The SEM images results showed that in control group,the smooth-surfaced sillicon dioxide(SiO?)particles exhibited clear fracture interfaces with resin matrix,with>50%particle exposure;the composite resin in group 0 showed similar morphology and large Zn-N-TiO? agglomerates with tight filler-matrix bonding;the composite resin in group 1,2,and 3 showed resin adhesion to SiO? surfaces(<50%particle exposure)and uneven fracture surfaces.Fractured SiO? spheres were observed in group 2.Filler distribution was uniform in group 1 and group 2,while the minor NP agglomeration occurred in group 3.The composite resin in control group showed the lowest EM.The EM was significantly improved in experimental groups,with group 3 having the highest value.Group 0 exhibited the lowest Vickers microhardness,showing statistically significant differences among other groups(P<0.05).The Vickers microhardness of the composite resion was gradually increased with the rising of Al?O? content.The resins in group 2 and group 3 achieved>45 HV hardness,representing increases of 29.73%and 33.82%compared with control group,and 51.34%and 56.28%compared with group 0.No significant differences in DC of the composite resin were found among groups(P>0.05).The depth of cure for all composite resin groups exceeded 4 mm,with no significance differences observed between various groups(P>0.05).The composite resin in group 0 showed the smallest WCA.The hydrophobicity of the composite resion was increased with the rising of Al?O? content,but all the WCA values remained<80°.The composite resin in group 3 had the largest WCA without statistical significance compared with group 2(P>0.05).Filler incorporation reduced the water sorption/solubility.The composite resin in the CCK-8 assay results showed the composite resins in all groups had RGR>75%,meeting in vitro safety standards.Conclusion:Reinforcing fillers impart superior antibacterial activity and mechanical properties to composite resins.Under experimental conditions,group 2 composite resin achieves optimal comprehensive performance in antibacterial efficacy and mechanical strength,demonstrating promising clinical application potential.

Objective To explore the clinical safety of plasma exchange(PE)combined with early continuous renal replacement therapy(CRRT)and its effects on coagulation and immune functions in patients with polytrauma and hypermyoglobinemia.Methods A non-randomized controlled study was conducted on 60 patients with severe polytrauma and myoglobinemia hospitalized in our department from January 2021 to December 2024.Based on different blood purification,the patients were divided a control group(CRRT)combined with conventional basic treatment,n=30)and an observation group(PE+CRRT and conventional basic treatment,n=30).Biochemical indicators(myoglobin,Mb),inflammation-related indicators,peripheral blood lymphocyte subsets,coagulation indicators,clinical-related indicators,and scores were observed and compared between the 2 groups before and after treatment.Results After 1,2 and 3 d of treatment,the levels of Mb,creatine kinase(CK),creatine kinase-MB isoenzyme(CK-MB),lactate dehydrogenase(LDH),serum creatinine(SCr),blood urea nitrogen(BUN),K+,C-reactive protein(CRP),procalcitonin(PCT),IL-6 and D-dimer(D-D),and white blood cell(WBC)count were significantly decreased in both groups(P<0.05).Among them,the observation group obtained obviously lower levels of all above indicators than the control group at the 3 time points(P<0.05).Additionally,notably shorter average length of total hospital stay,shorter average length of trauma intensive care unit stay,and lower score of acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)was observed in the observation group than the control group(P<0.05).There were no statistical differences in coagulation function indicators or T lymphocyte subsets between the 2 groups.No complications occurred.Conclusion For patients with polytrauma and hypermyoglobinemia,early application of PE+CRRT can effectively reduce serum myoglobin level,improve serum biochemical inicators,renal function and inflammatory status,and maintain homeostasis,but shows no effect on immune or coagulation functions.This approach is worthy of promoting in clinical practice.

Objective To establish models for real-time dynamic monitoring of intracellular cytoplasmic adenosine triphosphate(ATP)and mitochondrial ATP levels in cells in order to study the changes in metabolic processes.Methods The lentiviral plasmids of the cytoplasmic chemogenetic green fluorescent protein(GFP)ATP probe(Chemo-G)and those of the mitochondrial-localized chemogenetic GFP ATP probe(mito-Chemo-G)were constructed before being transfected into HEK293T together with the helper plasmids,respectively.Chemo-G and mito-Chemo-G lentiviruses were obtained.HeLa cells were infected with the lentivirus.Puromycin resistance selection and flow cytometry cell sorting were employed to identify and isolate the infected HeLa cells.The growth and GFP expressions of HeLa cells were observed.A live-cell imaging system was used for continuous imaging of the cells,with stimuli added at specific time points to alter intracellular ATP levels to observe changes in the fluorescence intensity of the ATP probe.Results Lentiviral plasmids containing Chemo-G and mito-Chemo-G sequences were constructed.Two cell lines which could stably express Chemo-G and mito-Chemo-G were established that exhibited strong growth and accurate intracellular fluorescence localization.Live-cell imaging revealed that after the addition of 2-deoxy-D-glucose(2-DG)into HeLa-Chemo-G,the fluorescence resonance energy transfer(FRET)/GFP ratio showed a decrease that was partially reversed by the addition of glucose.The FRET/GFP ratio increased after histamine stimulation,but rapidly decreased after the addition of oligomycin.Conclusion The Chemo-G and mito-Chemo-G lentiviral vectors and stably transfected cell lines HeLa-Chemo-G and HeLa-mito-Chemo-G are constructed,which provides reliable experimental models for studying cellular metabolism and changes in intracellular ATP levels.

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.

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.

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.

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.