Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

Objective: To evaluate the clinical value of combining low-dose energy spectrum CT with virtual un-enhanced(VUE) scanning and deep-learning image reconstruction(DLIR) in aortic CT angiography(CTA). Methods : In a prospective study, 94 patients scheduled for aortic CTA were randomized into two groups: a low-dose energy spectrum group and a standard 100 kVp enhancement group, with 47 patients in each. All patients initially underwent a true un-enhanced(TUE) scan at 120 kVp using adaptive statistical iterative reconstruction-V(ASIR-V) at 40% for image reconstruction. The low-dose group received enhanced scans using gemstone spectral imaging(GSI) mode with DLIR-H, producing 60 keV virtual monoenergetic images(VMIs) and VUE images. The standard group was scanned at 100 kVp, with images reconstructed using ASIR-V at 50%. Parameters were measured including CT values, noise(SD), signal-to-noise ratio(SNR), and contrast-to-noise ratio(CNR) for key vascular and muscular areas, alongside the effective radiation dose(ED). Two radiologists evaluated the image quality using a 5-point scale. Results : The low-dose group exhibited significantly higher SNR and CNR values in the ascending aorta, descending aorta, abdominal aorta, and common iliac artery compared to the standard group(P<0.05), with comparable subjective quality scores. The VUE images also demonstrated superior SNR values in the abdominal aorta, common iliac artery, and psoas major muscle, and CNR value in the ascending aorta compared to TUE images, with similar subjective quality. Importantly, the ED in the low-dose group was about 40% lower than that of the standard group. Conclusion Low-dose energy spectrum CT with DLIR in aortic CTA can significantly enhance SNR and CNR, while approximating the image quality of traditional TUE scans, thereby substantially reducing radiation exposure.

Objective To explore the clinical application of needle-embedding therapy for preventing and treating postoperative constipation in the patients with thoracolumbar vertebral fractures based on the theory of"preventing illness".Methods Eighty patients meeting the criteria for postoperative constipation af-ter thoracolumbar vertebral surgery in a tertiary hospital of Hangzhou City from January 2023 to February 2024 were selected as the study subjects.The patients were divided into the control group and experimental group by using the random number table method,40 cases in each group.The control group adopted the treat-ment of orally taking lactulose oral solution and the nursing such as routine postoperative food and drink and bed defecation training.The experimental group was given the needle-embedding therapy on the basis of rou-tine care.The gastrointestinal syndrome rating scale(GSRS)score,intra-abdominal pressure(IAP),abdomi-nal circumference,defecation and exhausting situation before and after intervention were performed the statis-tics and compared between the two groups.Results At 36,72 h after oeperation,the GSRS score,IAP and ab-dominal circumference in the both groups were significantly declined or decreased compared with those imme-diately after the operation,the above indicators in the experimental group were superior to those in the control group,and the differences were statistically significant(P＜0.01).The first exhausting and defecation time of the experimental group was earlier than that of the control group,and the difference was statistically signifi-cant(P＜0.01).Conclusion Under the basis of"preventing illness",the needing-embedding therapy has signif-icant therapeutic effects in preventing and treating postoperative constipation in thoracolumbar fractures,could effec-tively reduce IAP,alleviate the symptoms of constipation in the patients and improve their quality of life.

Objective:This study aimed to analyze the specific measures and practical effects of standardizing the management of patent conversion work in a certain district tertiary hospital, aiming to provide valuable references and guidance for improving patent conversion management for other hospitals of the same level.Methods:This study selected a series of standardized management measures taken by the hospital from July 2022 to December 2023 as the research object, including but not limited to the approval process before patent application, the combing and optimization of the approval process of patent conversion application, and the formulation and implementation of the tax reduction system and other policies.Results:The smooth implementation of various standardized management patent transformation measures in the hospital effectively improved the efficiency of patent quality control and patent conversion. Specifically, it was reflected in the shortening of the ″application conversion contract signing″ period, as well as a significant increase in the total number of patent implementation conversions and the total amount of conversion contracts signed.Conclusions:By standardizing the management of hospital patent conversion, not only can the efficiency and success rate of patent conversion be effectively improved, but also can effectively promote the development of hospital innovation and conversion work.

Objective To understand the use situation of Rush among the men who have sex with men(MSM)in Chongqing City and its influencing factors,so as to provide a basis for the formulation of relevant prevention and control measures.Methods The cross-sectional survey was adopted.The MSM population in Chongqing City were recruited through the network recruitment and referral of social organizations to conduct an anonymous electronic questionnaire survey to obtain the information such as demographic characteristics,sexual partners and sexual behavior characteristics in the past 6 months,Rush use,HIV and syphilis antibody testing.The X2 test and non-conditioned multi-factor Logistic regression analysis were used to analyze the in-fluencing factors of Rush use.Results A total of 494 MSM were surveyed,the Rush usage rate was 22.1％.The results of the multi-factor logistic regression analysis showed that the age of first time homosexuality be-havior＜18 years old(OR=2.715,95％CI:1.353-5.451),unprotected homosexual anal intercourse in near-ly 6 months(OR=2.237,95％CI:1.355-3.693),having multiple same-sex partners in nearly 6 months(OR=3.610,95％CI:1.449-8.993),same-sex casual partners in the nearly 6 months(OR=3.734,95％CI:2.221-6.280)were the risk factors for MSM using Rush.Conclusion The RUSH use rate among the MSM population in Chongqing City is high.The targeted intervention measures should be carried out,especially to strengthen the propaganda and education of the population who first have homosexual behavior under 18 years old,have unprotected homosexual anal intercourse in the nearly 6 months,have multiple homosexual perma-nent partners in the last 6 months,and have homosexual temporary partners,in order to reduce the use rate of Rush and thereby reduce the risk of HIV infection and transmission in this population.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Objective To validate the mechanism of Mori Cortex-Lycii Cortex(MCLC)in intervening acute lung injury(ALI)based on network pharmacology,molecular docking combined with animal experiments.Methods The TCMSP database was used to obtain the active components of MCLC;the SwissTargetPrediction database was used to predict the targets of active components;the GeneCards database and DisGeNET database were used to collect the disease targets of ALI;the key targets were screened by constructing a PPI network,and the key targets were subjected to GO and KEGG pathway enrichment;a drug-component-target-pathway network was constructed using Cytoscape software;AutoDock and PyMOL software were used to validate the molecular docking of some of the compounds and targets;LPS was used to establish a mouse model of ALI for experimental validation,and experimental validation was performed to main targets and pathways.Results Totally 44 active components of MCLC and 138 action targets were obtained;26 potential targets of MCLC intervention in ALI were obtained,mainly TNF,EGFR,NFKB1,MPO,TNFRSF1A,NOX4,etc.,and the key pathways were MAPK signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,etc.;molecular docking results showed that the core active components of MCLC and the main targets had strong binding activities;animal experiments showed that MCLC at medium and high dosages could effectively improve the lung histopathological damage in ALI mice,decrease the contents of IL-6 and TNF-α in serum(P<0.01),and increase IL-10 content(P<0.01);MCLC inhibited protein expressions of EGFR,PI3K,AKT,NF-κB p65 in lung tissue(P<0.01).Conclusion MCLC may intervene ALI by components such as quercetin and buddleoside,acting on targets including EGFR and TNF,through ulti-pathways of EGFR/PI3K/NF-κB signaling pathway,etc.

The cancer staging system of the American Joint Committee on Cancer (AJCC) is the most widely used clinical basis for tumor staging. In October 2023, AJCC released the staging system (ninth version) for the neuroendocrine tumors of stomach (NET), which has been implemented in January 2024. The ninth version of NET staging system mainly updated the histopathologic classification, diagnosis and staging methods, clinical and pathological staging, prognosis grade, tumor and non-tumor prognostic features. The update and implementation of the staging system provide a more detailed reference for the accurate diagnosis, staging and precise treatment of gastric neuroendocrine tumors. Moreover, it is convenient for clinicians to carry out clinical practice. The purpose of our article is to provide a high-level overview of the major changes in AJCC staging system (version 9) for gastric NET based on the latest evidence-based medical research.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.