Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Objective To integrate patient clinical information with single-cell sequencing analysis to identify key genes involved in organic erectile dysfunction(ED)in diabetic patients,and to further validate these findings using genome-wide association study(GWAS)data to pinpoint the genes associated with diabetic organic ED.Methods Single-cell RNA sequen-cing data were downloaded from the GSE206528 dataset,comprising samples from five patients including three individuals with-out ED or diabetes,and two patients diagnosed with diabetic ED.Data preprocessing,cell clustering,and annotation were per-formed using R,followed by extraction of microvascular endothelial cells for differential expression analysis.Enrichment analysis of the identified differentially expressed genes(DEGs)was conducted using the Hiplot platform.Expression quantitative trait loci(eQTL)single nucleotide polymorphisms(SNPs)corresponding to these DEGs were retrieved from the UK Biobank(UKB)da-tabase as exposures.ED(GWAS ID:ebi-a-GCST006956)was defined as the outcome variable.Mendelian randomization(MR)analysis was then performed to identify potential causal genes.Results Using the Seurat package,single-cell RNA se-quencing data from the five patients underwent quality control and integration.After cell type identification,a subset of microvas-cular endothelial cells was selected for differential expression analysis,resulting in the identification of 214 DEGs.Functional enrichment analysis revealed that these genes were significantly enriched in pathways related to diabetic complications,including the AGE-RAGE signaling pathway,TNF signaling pathway,and oxidative phosphorylation.Subsequently,MR analysis was per-formed on the 214 DEGs,using erectile dysfunction(ebi-a-GCST006956)as the outcome.Six genes were identified as potential causal genes including MYL9,NFIB,ENDOD1,DES,NRARP and HSPA1B.Conclusion These findings suggest that MYL9,NFIB,ENDOD1,DES,NRARP and HSPA1B may play a role in the progression of organic ED in diabetic patients.

Objective:To investigate relationship between IL-17/IL-23 immunoinflammatory axis and chronic heart failure(CHF)and clinical prognosis.Methods:A total of 112 patients with CHF in Chengde Central Hospital from January 2020 to Septem-ber 2021 were selected as observation group,and another 112 patients admitted to same period for healthy physical examination were selected as control group.Serum IL-17 and IL-23 levels of two groups were compared,relationship between serum IL-17 and IL-23 levels and degree of disease were analyzed;clinical data,serum IL-17 and IL-23 levels of patients with different prognosis were compared,relationship between serum IL-17 and IL-23 levels and clinical prognosis of CHF patients were analyzed.Predictive value of serum IL-17 and IL-23 levels on clinical prognosis of CHF patients was evaluated,and predictive value of each prediction scheme was compared.Results:Serum IL-17 and IL-23 levels were higher in observation group than control group(P<0.05);serum IL-17 and IL-23 levels of CHF patients were positively correlated with NYHA classification(P<0.05).Serum IL-17 and IL-23 levels were higher in patients with poor prognosis than in those with good prognosis(P<0.05).Serum IL-17 and IL-23 were independently associated with clinical prognosis of CHF patients,and the higher the serum IL-17 and IL-23 levels,the greater risk of poor clinical prognosis of CHF patients.AUC of serum IL-17 and IL-23 levels for predicting clinical prognosis of CHF patients were 0.787 and 0.726,respectively,and combined predicted AUC was 0.918(P<0.001);combined predicted AUC of serum IL-17 and IL-23 was significantly higher than single index(P<0.05).Conclusion:IL-17 and IL-23 levels in IL-17/IL-23 immunoinflammatory axis of CHF patients are significantly elevated and involve in disease occurence and development,whose clinical detection can help predict clinical prognosis of CHF.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.

AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

Objective To investigate the current status of self-care contributions of family caregivers of elderly stroke patients and analyse the influencing factors.Methods Using convenience sampling method,170 family caregivers of elderly stroke patients hospitalised in the Departments of Neurology of two Tier-ⅢA hospitals in Guiyang between June and October 2023 were selected.Data were collected using general information questionnaires,the mutuality scale(MS),stroke knowledge questionnaire,social support rating scale(SSRS)and the self-care contribution assessment scale for caregivers of elderly stroke patients.Multiple linear regression was used to identify the factors that influenced self-care contributions.Results The score of self-care contribution of family caregivers was 40.97±15.04,including 15.24±6.94 for self-care maintenance,9.44±4.97 for self-care monitoring and 16.30±5.18 for self-care management.Multiple linear regression analysis showed that self-care contributions were significantly influenced(P<0.05)by the duration of care of family caregivers,knowledge of stroke,mutuality and the social support,toally accounting for 43.1％of the variation.Conclusion Family caregivers of elderly stroke patients show low self-care contributions.Medical staff should offer additional support to family caregivers who have a shorter caregiving time.Improvement of mutuality,knowledge of stroke and social support can improve caregivers'self-care contributions.

Objective:To explore the efficacy and safety of the combination therapy of lenalidomide and rituximab (R2) for short-cycle maintenance therapy in patients with B-cell non-Hodgkin lymphoma (B-NHL).Methods:A retrospective case series study was conducted. The clinical data of 19 B-NHL patients who received R2 regimen maintenance therapy after achieving complete remission through chemotherapy or autologous hematopoietic stem cell transplantation at Dongguan Kanghua Hospital from February 2018 to January 2024 were collected, and the overall survival (OS), progression-free survival (PFS), adverse reactions, changes in lymphocyte subsets and cytokine levels before and after treatment were analyzed.Results:Among the 19 patients, there were 7 males and 12 females, with a median age [ M ( Q1, Q3)] of 49 (45, 65) years. The median follow-up time was 56 months, ranging from 5 to 77 months. The 1-year OS and PFS rates were 89.2% and 88.9%, respectively. The 2-year and 5-year PFS rates were both 83.2%, and the 2-year and 5-year OS rates were both 88.9%. Common adverse reactions included hematological adverse reactions and infections, with 4 cases (21.1%) experiencing grade 3-4 hematological adverse reactions and 4 cases (21.1%) experiencing infections. There was no statistically significant difference in the levels of lymphocyte subsets (total T cells, helper T cells, regulatory T cells, NK cells, B cells, and CD4/CD8) and cytokines [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ] before and after treatment (all P > 0.05). Conclusions:The R2 regimen for short-cycle maintenance therapy of B-NHL is effective and well tolerated by patients.

On the occasion of the 110th anniversary of the establishment of Chinese Medical Association, this article summarizes the important contributions of Cancer Research and Clinic which was one of the series of journals of Chinese Medical Association in academic exchanges, promotion of scientific research achievements and talent cultivation. It also analyzes the current situation and existing problems of Z hospital's human resources, and analyzes the different levels of talent needs of the hospital from the perspective of Maslow hierarchy of needs. It is hoped that with the high-quality resources of Cancer Research and Clinic, the hospital's talent cultivation can be effectively promoted, and the construction of national regional medical center can be assisted.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.