BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.

Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

Objective To develop and evaluate dietary and exercise intervention program for over-weight/obese patients with polycystic ovary syndrome(PCOS).Methods Seventy patients with over-weight/obese PCOS were prospectively selected as research subjects and divided into intervention group(n=35)and control group(n=35)according to random number table method.According to the completion of the intervention plan,29 cases were finally included in the intervention group and 28 cases in the control group.The control group was given conventional nursing intervention,while the intervention group was applied with the diet and exercise intervention program for overweight/obese patients with PCOS.Both groups were intervened for 3 months.The physical indicators,PCOS sign scores,natural pregnancy rate,degree of self-body image distress(Multidimensional Self-body Im-age Relationship Questionnaire-Appearance Subscale)and self-efficacy level(Self-efficacy Scale)before and after the intervention were compared between the two groups.The occurrence of adverse reactions during the intervention period between the two groups were compared.Results After 1 month and 3 months of intervention,the body mass index(BMI)and PC OS sign score of the pa-tients in the intervention group were significantly lower than those in the control group(P＜0.05).The natural conception rate of the intervention group was 34.48％(10/29),which was significantly higher than 10.71％(3/28)of the control group(P＜0.05).After 1 month and 3 months of inter-vention,the scores of the self-body image relationship-appearance subscale of the patients in the inter-vention group were significantly higher than those in the control group(P＜0.001).After 3 months of intervention,the score of the Self-efficacy Scale of patients in the intervention group was significantly higher than that in the control group(P＜0.001).During the intervention period,no adverse reac-tions caused by diet and exercise intervention occurred in either group.Conclusion Implementing a diet and exercise intervention program for overweight/obese patients with PCOS is beneficial for re-ducing patients' BMI,increasing the natural pregnancy rate,improving self-body image disorders,and enhancing self-efficacy.

Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

As a kind of immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are an important component of the immune microenvironment. MDSCs play a significant role in promoting tumor immune escape. In addition, non-immunological functions such as promoting angiogenesis can also promote tumor development with the deepening of research. MDSCs can promote tumor angiogenesis directly through vascular endothelial growth factor signaling pathway, or promote tumor growth and angiogenesis by secreting cytokines such as matrix metalloprotein-9, basic fibroblast growth factor, angiogenic peptide Bv8, platelet derived growth factor, exosomes, or interacting with other cells. Exploring the expansion, activation, recruitment and angiogenesis mechanism of MDSCs will provide new ideas for regulating the individualized diagnosis and treatment based on targeted MDSCs.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.