OBJECTIVES: To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats. METHODS: Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg^－¹·d^－¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. RESULTS: Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified. CONCLUSIONS This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.
Animals ; Male ; Proteomics/methods* ; Rats, Wistar ; Flavonoids/therapeutic use* ; Rats ; Brain Edema/etiology* ; Altitude Sickness/metabolism* ; Protein Interaction Maps

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

Objectives:To summarize the relevant evidence of non-invasive cardiac output monitoring management in critically ill patients and provide evidence-based basis for strengthening the standardization and accuracy of non-invasive cardiac output monitoring by clinical medical staff.Methods:We searched UpToDate,British Medical Journal Best Practice Database,The UK National Institute of Clinical Medicine guideline library,PubMed,Embase,American Society of Critical Care Medicine,American Association of Critical Care Nurses,Wanfang database,China Knowledge Network,SinoMed and other databases to collect relevant clinical decisions,guidelines,best practices,evidence summaries,systematic reviews,expert consensuses and randomized controlled trials related to non-invasive cardiac output monitoring management.The search period is from the inception to August 2023.After screening and quality evaluation by the evidence-based team,relevant evidence that meets the standards was extracted.Results:A total of 11 articles were obtained,including 7 systematic reviews,4 expert consensus.Finally,20 best evidences were obtained about the non-invasive cardiac output monitoring management in critically ill patients,including the patients suitable for non-invasive cardiac output monitoring,correlation with the invasive cardiac output monitoring,and the source of error in the monitoring process,involving 5 aspects such as monitoring population,clinical application,interference factors,precautions and personnel training.Conclusions:Clinical medical staffshould strengthen the training of non-invasive cardiac output monitoring technology in critically ill patients,and appropriate practical evidence should be selected in combination with the specific clinical situation to improve the application standardization and measurement accuracy of non-invasive cardiac output monitoring in critically ill patients.

Objective The study aimed to investigate the predictive efficacy of contrast-enhanced ultrasound combined with telomerase reverse transcriptase(TERT)promoter mutation in constructing nomogram model for the prediction of concomitant cervical lymph node metastasis(CLNM)in papillary thyroid microcarcinoma(pTMC).Methods A total of 202 patients with pTMC who underwent partial or total thyroidectomy+lymph node dissection at our hospital from January 2021 to March 2024 were selected.Then,they were divided into the CLNM group(97 patients)and the non-CLNM group(105 patients)according to whether they had concomitant CLNM on postoperative pathological examination.General data and ultrasound(conventional ultrasound and contrast-enhanced ultrasound)characteristics were collected from all patients with pTMC,and Sanger sequencing was used to detect TERT promoter mutations.The influencing factors of pTMC complicated by CLNM were analyzed by single-factor and multifactorial unconditional logistic regression;the nomogram model of pTMC complicating CLNM with contrast-enhanced ultra-sound combined with TERT promoter mutation was constructed by RStudio 4.4.1 software,and the consistency and net benefit of the nomogram model were evaluated by using calibration curves,decision curves,and C-indexes,and the Hosmer-Lemeshow test for goodness of fit of the nomogram model;The predictive efficiency of the nomogram model constructed by combining contrast-enhanced ultrasound and TERT promoter mutation for pTMC complicated by CLNM was evaluated by plotting receiver operating characteristic(ROC)curves using MedCalc22.023 software.Results After postoperative pathological examination,the incidence of CLNM in 202 patients with pTMC was 48.02%(97/202).Univariate analysis showed that thyroglobulin antibodies,number of lesions,aspect ratio,micro-calcifications,enhancement time,enhancement mode,enhancement intensity,capsular continuity,and TERT promoter mutations were associated with pTMC complicating CLNM(P<0.05).Multifactorial unconditional logistic regression showed that multifocal tumours(OR=3.487,95%CI:1.641～7.406,P=0.001),microcalcifications(OR=4.484,95%CI:2.113～9.516,P<0.001),equal or high enhancement(OR=3.187,95%CI:1.460～6.957,P=0.004),disruption of peritoneal continuity(OR=2.201,95%CI:1.051～4.608,P=0.036),and TERT promoter mutation positivity(OR=4.460,95%CI:2.132～10.103,P<0.001)were the independent risk factors for pTMC complicating CLNM.A contrast-enhanced ultrasound combined TERT promoter mutation nomogram model was constructed based on independent risk factors for pTMC complicating CLNM[Logit(p)=-4.486+1.350×number of foci+1.399×microcalcifications+2.124×intensity of enhancement+1.524×capsular continuity+2.175×TERT promoter mutations].The C-index of this nomogram model was 0.899(95%CI:0.893～0.905),the calibra-tion curve alignment was close to the ideal curve,the decision curve was higher than the two extreme curves,and the Hosmer-Lemeshow test showed a P>0.05.The ROC curve analysis showed that the nomogram model constructed with contrast-enhanced ultrasound combined with TERT promoter mutations predicted CLNM in pTMC with an area under the curve of 0.899.This was significantly higher than the area under the curves for contrast-enhanced ultra-sound alone(0.857)and TERT promoter mutations alone(0.697)(P<0.05).Conclusion The contrast-enhanced ultrasound combined with TERT promoter mutations to construct a nomogram model has high predictive efficiency for pTMC complicating CLNM.

Objective To evaluate the effectiveness of virtual reality technology in breast cancer chemotherapy patients.Methods Databases were searched for randomized controlled trials literature on the effects of virtual reality technology on interventions for breast cancer chemotherapy patients.The time frame of the search was from construction of the database to February 2024.After screening the relevant literature by two researchers based on predetermined inclusion and exclusion criteria,information and methodological quality assessment were extracted.Eight literature articles were included in this study.Data analysis was performed using Revman 5.4 software,and data that could not be merged were analyzed descriptively.Results Meta-analysis showed that virtual reality technology significantly improved anxiety,depression,cancer-caused fatigue,cognitive function and quality of life of breast cancer chemotherapy patients.Conclusion Virtual reality technology as a non-pharmacological intervention can effectively improve anxiety,depression,cancer-caused fatigue,cognitive function,and quality of life of breast cancer chemotherapy patients.

Objective To evaluate the effectiveness of virtual reality technology in breast cancer chemotherapy patients.Methods Databases were searched for randomized controlled trials literature on the effects of virtual reality technology on interventions for breast cancer chemotherapy patients.The time frame of the search was from construction of the database to February 2024.After screening the relevant literature by two researchers based on predetermined inclusion and exclusion criteria,information and methodological quality assessment were extracted.Eight literature articles were included in this study.Data analysis was performed using Revman 5.4 software,and data that could not be merged were analyzed descriptively.Results Meta-analysis showed that virtual reality technology significantly improved anxiety,depression,cancer-caused fatigue,cognitive function and quality of life of breast cancer chemotherapy patients.Conclusion Virtual reality technology as a non-pharmacological intervention can effectively improve anxiety,depression,cancer-caused fatigue,cognitive function,and quality of life of breast cancer chemotherapy patients.

Objective The study aimed to investigate the predictive efficacy of contrast-enhanced ultrasound combined with telomerase reverse transcriptase(TERT)promoter mutation in constructing nomogram model for the prediction of concomitant cervical lymph node metastasis(CLNM)in papillary thyroid microcarcinoma(pTMC).Methods A total of 202 patients with pTMC who underwent partial or total thyroidectomy+lymph node dissection at our hospital from January 2021 to March 2024 were selected.Then,they were divided into the CLNM group(97 patients)and the non-CLNM group(105 patients)according to whether they had concomitant CLNM on postoperative pathological examination.General data and ultrasound(conventional ultrasound and contrast-enhanced ultrasound)characteristics were collected from all patients with pTMC,and Sanger sequencing was used to detect TERT promoter mutations.The influencing factors of pTMC complicated by CLNM were analyzed by single-factor and multifactorial unconditional logistic regression;the nomogram model of pTMC complicating CLNM with contrast-enhanced ultra-sound combined with TERT promoter mutation was constructed by RStudio 4.4.1 software,and the consistency and net benefit of the nomogram model were evaluated by using calibration curves,decision curves,and C-indexes,and the Hosmer-Lemeshow test for goodness of fit of the nomogram model;The predictive efficiency of the nomogram model constructed by combining contrast-enhanced ultrasound and TERT promoter mutation for pTMC complicated by CLNM was evaluated by plotting receiver operating characteristic(ROC)curves using MedCalc22.023 software.Results After postoperative pathological examination,the incidence of CLNM in 202 patients with pTMC was 48.02%(97/202).Univariate analysis showed that thyroglobulin antibodies,number of lesions,aspect ratio,micro-calcifications,enhancement time,enhancement mode,enhancement intensity,capsular continuity,and TERT promoter mutations were associated with pTMC complicating CLNM(P<0.05).Multifactorial unconditional logistic regression showed that multifocal tumours(OR=3.487,95%CI:1.641～7.406,P=0.001),microcalcifications(OR=4.484,95%CI:2.113～9.516,P<0.001),equal or high enhancement(OR=3.187,95%CI:1.460～6.957,P=0.004),disruption of peritoneal continuity(OR=2.201,95%CI:1.051～4.608,P=0.036),and TERT promoter mutation positivity(OR=4.460,95%CI:2.132～10.103,P<0.001)were the independent risk factors for pTMC complicating CLNM.A contrast-enhanced ultrasound combined TERT promoter mutation nomogram model was constructed based on independent risk factors for pTMC complicating CLNM[Logit(p)=-4.486+1.350×number of foci+1.399×microcalcifications+2.124×intensity of enhancement+1.524×capsular continuity+2.175×TERT promoter mutations].The C-index of this nomogram model was 0.899(95%CI:0.893～0.905),the calibra-tion curve alignment was close to the ideal curve,the decision curve was higher than the two extreme curves,and the Hosmer-Lemeshow test showed a P>0.05.The ROC curve analysis showed that the nomogram model constructed with contrast-enhanced ultrasound combined with TERT promoter mutations predicted CLNM in pTMC with an area under the curve of 0.899.This was significantly higher than the area under the curves for contrast-enhanced ultra-sound alone(0.857)and TERT promoter mutations alone(0.697)(P<0.05).Conclusion The contrast-enhanced ultrasound combined with TERT promoter mutations to construct a nomogram model has high predictive efficiency for pTMC complicating CLNM.

Objectives:To summarize the relevant evidence of non-invasive cardiac output monitoring management in critically ill patients and provide evidence-based basis for strengthening the standardization and accuracy of non-invasive cardiac output monitoring by clinical medical staff.Methods:We searched UpToDate,British Medical Journal Best Practice Database,The UK National Institute of Clinical Medicine guideline library,PubMed,Embase,American Society of Critical Care Medicine,American Association of Critical Care Nurses,Wanfang database,China Knowledge Network,SinoMed and other databases to collect relevant clinical decisions,guidelines,best practices,evidence summaries,systematic reviews,expert consensuses and randomized controlled trials related to non-invasive cardiac output monitoring management.The search period is from the inception to August 2023.After screening and quality evaluation by the evidence-based team,relevant evidence that meets the standards was extracted.Results:A total of 11 articles were obtained,including 7 systematic reviews,4 expert consensus.Finally,20 best evidences were obtained about the non-invasive cardiac output monitoring management in critically ill patients,including the patients suitable for non-invasive cardiac output monitoring,correlation with the invasive cardiac output monitoring,and the source of error in the monitoring process,involving 5 aspects such as monitoring population,clinical application,interference factors,precautions and personnel training.Conclusions:Clinical medical staffshould strengthen the training of non-invasive cardiac output monitoring technology in critically ill patients,and appropriate practical evidence should be selected in combination with the specific clinical situation to improve the application standardization and measurement accuracy of non-invasive cardiac output monitoring in critically ill patients.

Objective:To investigate the changes of exam scores of retrained peritoneal dialysis (PD) operators (patients, family members, or nannies) with an internal of one year during COVID-19 epidemic and provide basis for targeted training.Methods:It was a cross-sectional survey study. The maintenance PD patients who participated in two trainings with an interval of one year during COVID-19 epidemic from November 1, 2019 to February 28, 2021 in Department of Nephrology in Peking University People's Hospital were enrolled. During COVID-19 epidemic, retraining was extended from once every six months to once a year. The clinical data were collected, the self-designed training exam score table including theoretical knowledge and operational skills assessment was used to investigate the exam scores of two trainings, and the total exam scores and sub-item scores of PD operators before and after one year were compared. Logistic regression analysis was used to analyze the associated factors of the reduction of exam scores.Results:A total of 59 patients were enrolled, with 35 males (59.32%), age of (58.41±14.52) years, and dialysis duration of 42 (12, 84) months. There were 54 patients (91.53%) operating by themselves, 22 operators (37.29%) having college degree or above, and 35 operators (59.32%) having decreased exam scores. The total exam scores were 83.17±7.90 and 80.61±8.20 before and after one year, respectively ( t=2.732, P=0.008). In the six contents of itemized scoring, compared with one year ago, the exam scores of complication treatment ( t=4.928, P<0.001) and self-monitoring ( t=3.222, P=0.002) were significantly decreased. There was no statistically significant difference in the exam scores of environment and hygiene, dialysate replacement operation, exit nursing and diet before and after one year (all P>0.05). The total exam scores in patients with dialysis duration <12 months and 36-60 months after one year were significantly lower than before one year ( t=2.309, P=0.041; t=3.086, P=0.009). There was no statistically significant difference in the exam scores of PD operators with dialysis duration of 12-<36 months and >60 months before and after one year (both P>0.05). Logistic regression analysis showed that dialysis duration was an independent associated factor of exam scores reduction (dialysis duration 36-60 months/>60 months, OR=6.233, 95% CI 1.035-37.529, P=0.046). Conclusions:During COVID-19 epidemic, the reduced frequency of retraining reduces the training exam scores of PD operators, especially in patients with dialysis duration of 36-60 months. The weak points are focused on complication management and self-monitoring. Training should be strengthened for key patients and key contents if regular retraining is not possible due to special circumstances.

Objective:To explore the mechanism by which Pien Tze Huang improves liver Kupffer cell damage induced by lipopolysaccharide (LPS) by regulating the expression of miR-155.Methods:LPS induced liver Kupffer cells to establish a cell injury model to simulate septic liver injury. RT-qPCR was used to detect the expression of miR-155 in damaged cells, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the inflammatory response and apoptosis of damaged cells. Then we treated LPS-induced Kupffer cells with Pien Tze Huang at different concentrations (0 mg/L, 5 mg/L, 10 mg/L and 15 mg/L), and detected the expression of miR-155 in the cells, the inflammatory response of the cells and Apoptosis rate. MiR-155 was silenced in the cell injury model, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the effect of miR-155 on inflammatory response and apoptosis of model cells. Overexpression of miR-155 in damaged cells treated with Pien Tze Huang was used to detect changes in cellular inflammatory response and apoptosis. Data are expressed in the form of mean ± standard deviation, and each group of data is analyzed using t test or one-way analysis of variance.Results:In the LPS-induced liver Kupffer cell injury model, the expression of miR-155 was significantly increased ( P<0.05), the expression levels of pro-inflammatory factors IL-6 and TNF-α were significantly increased, and the anti-inflammatory factor IL-10 was significantly increased. was inhibited ( P<0.05), and the cell apoptosis rate was significantly increased ( P<0.05). After Pien Tze Huang treatment, the expression of miR-155 in damaged liver cells was inhibited ( P<0.05), the levels of cellular inflammatory factors IL-6 and TNF-α were inhibited, and the expression of anti-inflammatory factor IL-10 was promoted ( P<0.05). Inhibit cell apoptosis ( P<0.05). Silencing miR-155 reduced the inflammatory response and apoptosis rate of cells ( P<0.05). Overexpression of miR-155 can reverse the effect of Pien Tze Huang on liver cell injury ( P<0.05). Conclusions:In the model of LPS-induced liver Kupffer cell injury, Pien Tze Huang can inhibite the inflammatory response and apoptosis of cells by inhibiting the expression of miR-155.