Precision therapy has become an important approach in modern medicine,with the goal of providing individualized treatment according to the characteristics of individual patients.The successful development of precision medicine depends on the application of preclinical cancer models.Patient-derived organoid(PDO)xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models.This type of model can not only maintain the heterogeneity of the original tumor,but also has additional advantages,such as large-scale cultivation,high-throughput drug screening in vitro and drug sensitivity testing in vivo.It is an innovative,precise preclinical disease model.In this review,we summarize the basic characteristics of the PDO xenograft model,analyze its construction method and influencing factors,further discuss its application in precision therapy,with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.

Objective To systematically construct patient-derived tumor organoid(PDO)and patient-derived xenograft(PDX)models of prostate cancer(PCa),and to explore the inhibitory effect and mechanism of gambogic acid(GA)on PCa.Methods The PubChem,SwissTargetPrediction,SuperPred,SEA,GeneCards,OMIM,and STRING databases,and the Venny 2.1.0 online website,Cytoscape 3.8.2,and DAVID software were used to construct a protein-protein interaction network.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were carried out,and visualization processing was performed to identify the targets and pathways of GA acting on PCa.GA was applied to PDOs and PCa cells(22Rv1,PC3,and DU145)for 48 hours and its effects on cell viability were assessed by CellTiter-Glo and CCK-8 assays.Changes in gene and protein levels of the targets were analyzed by quantitative real-time polymerase chain reaction and Western Blot,respectively.The PDX model was treated with GA and the tumor volume and weight were measured.Changes in expression levels of the targets in tumor tissues were detected by immunohistochemistry.Results Network pharmacology identified signal transducer and activator of transcription 3(STAT3)as the core target of GA inhibiting PCa,related to the hypoxia-inducible factor(HIF)-1α signaling pathway.GA reduced the viability of cells and PDOs and significantly down-regulated HIF-1α,STAT3,and P-STAT3 protein levels.In vivo experiments,tumor volume and weight were significantly reduced in the GA group,and immunohistochemistry showed that STAT3 and HIF-1α expression levels were decreased.Conclusions The clinically representative PDO and PDX models,combined with cell lines,verified the prediction result of network pharmacology,confirming a significant killing effect of GA on PCa,possibly via a mechanism related to the STAT3/HIF-1α signaling pathway.

Objective To systematically construct patient-derived tumor organoid(PDO)and patient-derived xenograft(PDX)models of prostate cancer(PCa),and to explore the inhibitory effect and mechanism of gambogic acid(GA)on PCa.Methods The PubChem,SwissTargetPrediction,SuperPred,SEA,GeneCards,OMIM,and STRING databases,and the Venny 2.1.0 online website,Cytoscape 3.8.2,and DAVID software were used to construct a protein-protein interaction network.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were carried out,and visualization processing was performed to identify the targets and pathways of GA acting on PCa.GA was applied to PDOs and PCa cells(22Rv1,PC3,and DU145)for 48 hours and its effects on cell viability were assessed by CellTiter-Glo and CCK-8 assays.Changes in gene and protein levels of the targets were analyzed by quantitative real-time polymerase chain reaction and Western Blot,respectively.The PDX model was treated with GA and the tumor volume and weight were measured.Changes in expression levels of the targets in tumor tissues were detected by immunohistochemistry.Results Network pharmacology identified signal transducer and activator of transcription 3(STAT3)as the core target of GA inhibiting PCa,related to the hypoxia-inducible factor(HIF)-1α signaling pathway.GA reduced the viability of cells and PDOs and significantly down-regulated HIF-1α,STAT3,and P-STAT3 protein levels.In vivo experiments,tumor volume and weight were significantly reduced in the GA group,and immunohistochemistry showed that STAT3 and HIF-1α expression levels were decreased.Conclusions The clinically representative PDO and PDX models,combined with cell lines,verified the prediction result of network pharmacology,confirming a significant killing effect of GA on PCa,possibly via a mechanism related to the STAT3/HIF-1α signaling pathway.

Precision therapy has become an important approach in modern medicine,with the goal of providing individualized treatment according to the characteristics of individual patients.The successful development of precision medicine depends on the application of preclinical cancer models.Patient-derived organoid(PDO)xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models.This type of model can not only maintain the heterogeneity of the original tumor,but also has additional advantages,such as large-scale cultivation,high-throughput drug screening in vitro and drug sensitivity testing in vivo.It is an innovative,precise preclinical disease model.In this review,we summarize the basic characteristics of the PDO xenograft model,analyze its construction method and influencing factors,further discuss its application in precision therapy,with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.

Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.

A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer׳s disease (AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Levels of iNOS and the cytokines TNF, IL-1and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1 (HO-1) in the cortex and hippocampus. PHPB reduced the levels of iNOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.

OBJECTIVE: To explore the relationship between noise-induced hearing loss, hypertension and abnormal electrocardiogram(ECG) in noise-exposed workers. METHODS: A judgment sampling method was adopted to select 555 male workers with hearing loss as study group and 555 male workers with normal hearing as control group in the similar environment in an automobile manufacturing enterprise in Guangzhou. Pure tone audiometry,blood pressure measurement and ECG examination were performed in both groups to analyze the relationship between hearing loss and hypertension and abnormal ECG. RESULTS: The prevalence rate of hypertension and abnormal ECG was higher in the hearing loss group than the control group(P < 0. 05). The multiple logistic regression analysis showed that after adjusting confounding factors such as age,seniority,body mass index,drinking et al,the risk of hypertension in hearing loss group was higher than the control group(P < 0. 05) and the odds ratio(OR) was 2. 255 [95% confidence interval(CI) : 1. 093-4. 655 ],while adjusting the confounding factor of drinking,the risk of ECG abnormalities in hearing loss group was higher than the control group(P < 0. 05) and the OR was 1. 408(95% CI: 1. 027-1. 930). CONCLUSION: Workers exposed to noise with hearing loss increase the risk of hypertension and abnormal ECG.

Objective To observe the preventive effect of different doses of diacerein on acute gout model rats and to explore its possible mechanism.Methods A total of 30 Wistar rats and were randomly assigned to the normal control group, the negative control (normal saline control group, and positive (colchicine) control group, diacerein low dose group, medium iddle dose group and high dose group.Except the normal control group that were given normal saline, other groups received colchicine (0.3 mg·kg-1 ·d-1), diacerein (10 mg·kg-1·d-1, 50 mg·kg-1·d-1 and 100 mg·kg-1·d-1) for 8 days respectively, and prepared acute gouty arthritis model on the 6th day, then observed rats joint swelling and gait at 2 h, 6 h, 8 h, 24 h and 48 h after the acute gouty arthritis model were established.After 48 h, the rats were killed, the serum and joint leachate of the rats were collected to test interleukin (IL)-1β and tumor necrosis factor (TNF)-α.One-way analysis of variance (ANOVA), LSD t test and Kruskal-Wallis rank sum test were used for statistical analysis.Results Compared with the normal group, joint swelling of the rats in the negative control group became significantly swollen at 2 h after the model was established,at and it reached the peak at 8 h reached the peak, then decreased gradually and remitted obviously at 48 h obviously remission.Joint swelling of the ccolchicine group and diacerein high dose group joint swelling [(0.106±0.081) cm, (0.112±0.030) cm] and ankle joint inflammation index score [(2.8±1.7), (3.16±0.75)] were significantly decreased compared with the negative control group [(0.208±0.078) cm, (4.7±1.6);P＜0.05].In addition, compared with the negative control group, the gait of diacerein high dose group was significantly improved (F=7.552, F=1.859, P＜0.05), colchieine group and diacerein high dose group, the serum and joint leaching liquid TNF-α and IL-1 levels also decreased significantly (P＜0.05).Conclusion Diacerein in any In each dosage group of has a certain preventive and therapeutic effect on rats gouty arthritis rats, especially in high dose group, the anti-inflammatory mechanism may be down-regulating the expression of proinflammatory mediators such as IL-1 beta and TNF-α.

This study is designed to compare the distribution, function and cell cycle of rat osteoblast cultured on sandblasting and acid-alkali base titanium surface versus that cultured on carbonated hydroxyapatite titanium surface; the aim is to probe the influences of different surfaces on the function of osteoblasts. SD rat's osteoblasts were primary-cultured, passaged to the 4th generation and then cultured on the two kinds of surfaces. The cellular modality was observed using an inverted microscopy analyzing system. Proliferation was examined by MTT chromatometry and depicted by growth curve. Expression of alkaline phosphatase (ALP) was detected by Enzyme-Linked Immunosorbent Assay. The cell apoptosis and proliferation were examined by flow cytometry. The proliferation curve and index of the osteoblasts on the two kinds of surfaces were almost the same. However, on the carbonated hydroxyapatite group, the level of alkaline phosphatase expression of osteoblasts was higher and kept longer than the other one. In conclusion, the elements on the titanium surface influence the cell function, and the surface with rich PO4(3-) and Ga2+ can enhance the mineralization function of rat osteoblast.
Alkaline Phosphatase ; chemistry ; pharmacology ; Animals ; Carbonates ; chemistry ; pharmacology ; Cell Adhesion ; drug effects ; Cell Cycle ; drug effects ; Cells, Cultured ; Hydroxyapatites ; chemistry ; pharmacology ; Osteoblasts ; cytology ; Rats ; Rats, Sprague-Dawley ; Surface Properties ; Titanium ; chemistry

The aim of this study is to elucidate the protective and anti-apoptotic effects of insulin-like growth factor 1 ( IGF-1 ) against β-amyloid (Aβ) and investigate the effect of IGF-1 on Aβ-induced tau phosphorylation. Cell viability was measured using the MTT (3-(4,5-dimethylthiazolyl-2 )-2,5-diphenyltetrazolium bromide) assay, early apoptosis and late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide (PI) double staining, and morphology was examined by Hoechst 33342 staining. Tau phosphorylation was detected using AT8 immunostaining. Preincubation of cultured rat hippocampal neurons with IGF-1 for 24 h prevented cytotoxicity induced by Aβ25-35 for 48 h. The MTT value significantly increased from 54.51% to 61.8% of the control group, and the percentage of Hoechst 33342-positive cells decreased from 30.77% to 22.81%. Incubation with Aβ25-35 for 48 h caused a marked increase in the percentages of Annexin V-FITC single-labeled cells (Annexin V +/PI-) and Annexin V/PI double-stained cells (Annexin V +/PI + ) (3.41% and 19.47% , respectively), which were significantly decreased by pretreatment with 100 ng/ml of IGF-1 for 24 h (to 2.98% and 15.16% , respectively). Aβ25-35 treatment increased tau phosphorylation and AT8 positive cells were 41.84%. This effect could be inhibited by different concentrations of IGF-1. Our findings showed that IGF-1 protected against Aβ-induced cytotoxicity, decreased the percentage of early and late apoptosis/necrosis cells, and inhibited tau phosphorylation, which may be the cellular mechanisms for its neuroprotective action.