BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Objective To investigate whether carotid artery stenting （CAS） is a protective factor against the progression of white matter hyperintensity （WMH） volume in patients with carotid artery stenosis. Methods A prospective study was conducted for the clinical， imaging， and follow-up data of patients with carotid artery stenosis who were treated in Zhejiang Provincial People's Hospital from January 2021 to June 2023. A total of 99 participants were included in this study， among whom 48 received CAS treatment （CAS group） and 51 did not receive CAS treatment （non-CAS group）. The two groups were analyzed in terms of baseline data and WMH volume during the 1-year follow-up. Results There were no significant differences in baseline data between the two groups （P>0.05）. There was no significant difference in overall WMH volume after follow-up between the two groups （P>0.05）， but compared with the non-CAS group， the CAS group showed a significantly lower degree of the progression of WMH volume within one year （-0.27 ml vs 2.82 ml， P<0.001）. There was a significant difference in the proportion of patients with new-onset stroke within one year between the CAS group and the non-CAS group （18.75% vs 37.25%， P=0.041）. The binary logistic regression analysis showed that CAS was an independent protective factor against the progression of WMH volume（OR=-0.37， 95%CI -0.78 to -0.03，P=0.046） and new-onset stroke within one year （OR=0.28， 95% CI 0.09 to 0.83， P=0.022）. Conclusion CAS is a protective factor against the progression of WMH volume and can effectively reduce the risk of stroke recurrence in patients with carotid artery stenosis.

Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters，such as R.E.N.A.L.，PADUA，C-Index，which are used to guide the clinical selection of surgical modalities，and predict perioperative complications and prognosis. In this paper，various scoring systems are grouped into three major categories according to their functions：prediction of surgical complexity，prediction of complications，and prediction of prognosis. The contents，characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists，enhance their surgical decision-making ability，and improve the clinical outcomes.

ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P＞0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.

MiR-138-5p is a microRNA that plays an important regulatory role in the pathogenesis of osteoarthritis.MiR-138-5p regulates various biological processes,including inflammation,cell apoptosis and proliferation,and matrix degradation in osteoarthritis,by modulating signaling pathways including nuclear factor-κB,Wnt/β-catenin,and phosphoinositide 3-kinase/AKT.This review summarizes the research progress regarding the mechanism of miR-138-5p in osteoarthritis.

Objective:To explore the characteristics of gene mutation in patients with myelodysplastic syndrome (MDS) and its correlation with clinical features. Methods:From January 2017 to December 2021,172 patients with MDS in The First Affiliated Hospital of Bengbu Medical University were analyzed retrospectively. Fourteen high frequency genes related to MDS were detected,and the relationship between gene mutation and clinical characteristics of patients as well as revised International Prognostic Scoring System (IPSS-R) was analyzed. The impact of gene mutations on prognosis was explored. Results:Among 172 patients,there were 101 males and 71 females,with a median age of 67 (15-89) years old,and gene mutations were detected in 88 cases (51.2％). The genes with mutation incidence>5％ were arranged in descending order as follows:TET2 (16.9％),RUNX1 (12.8％),ASXL1 (12.2％),CEBPA (8.1％),TP53 (7.0％) and DNMT3A (6.4％). According to biological functional classification,the genes with the highest mutation frequency were epigenetic regulatory genes (36.6％). The proportion of primitive bone marrow cells in mutation group was higher than that in non-mutation group (P<0.001). The incidence of gene mutation varied in different MDS subtypes,and the difference was statistically significant (P<0.05). The mutation incidence in IPSS-R higher risk group (IPSS-R score>3.5) was 65.7％,which was significantly higher than 30.0％ in IPSS-R lower risk group (IPSS-R score ≤3.5) (P<0.05),and there was a statistically significant difference in the incidence of TP53 gene mutation between the two groups (P<0.05). Multivariate Cox survival analysis showed that TP53,NPM1 and TET2 gene mutation were independent risk factors affecting prognosis. Conclusion:MDS patients are prone to gene mutation,and the increasing number of mutations and the presence of TP53,NPM1 and TET2 gene mutation may be factors affecting the prognosis.

Objective:To analyze the application value of MCV,MCH and HbA2 in screening for thalassemia in the population of childbearing age in Quanzhou area,and to determine the optimal screening cut-off value of relevant indicators in this area. Methods:2725 couples of childbearing age were included in the study and underwent routine blood test,capillary hemoglobin electrophoresis,and α and β thalassemia gene test. Statistical methods were used to analyze the distribution of thalassemia genotypes,and compare the performance of MCV,MCH,and HbA2 in screening various types of thalassemia. According to the ROC curve,the best cut-off values of MCV,MCH and HbA2 in screening for thalassemia in this area were determined. Results:In this study,a total of 1801 thalassemia carriers were detected,including 1341 cases of α-thalassemia,420 cases of β-thalassemia,and 40 cases of αβ compound thalassemia. The most common genotypes of α-thalassemia and β-thalassemia were--SEA/αα and β654/βN,respectively. ROC curves were drawn to evaluate the performance of MCV,MCH and HbA2 in screening for α-thalassemia,mild β-thalassemia,αβ compound thalassemia,silent α-thalassemia,mild α-thalassemia,and intermediate α-thalassemia. The maximum areas under the curves (AUC) were 0.747,0.865,0.724,0.486,0.812,0.841;0.747,0.846,0.703,0.479,0.796,0.903;0.613,0.980,0.909,0.465,0.674,0.996,respectively;and the best cut-off values corresponding to the three screening indicators were 76.15fl,71.95fl,77.35fl,86.15fl,75.41fl,61.15fl;24.35pg,21.51pg,25.45pg,28.65pg,24.01pg,20.51pg;2.45％,3.05％,3.55％,3.25％,2.45％,1.65％,respectively. Conclusion:The levels of MCV,MCH and HbA2 are correlated with the phenotype of thalassemia,and the detection of these indicators is of great significance for the prevention and control of thalassaemia.