Background and purpose:Patients with prostate cancer(PCa)have consistently shown suboptimal responses to immunotherapy,which may be closely related to the immunosuppressive state of the PCa tumor microenvironment.MYC,a key transcription factor in cancer cells,is involved in cell proliferation,differentiation,apoptosis and immune surveillance by regulating the expression of intracellular genes.This study aimed to elucidate the mechanisms through which MYC fosters an immunosuppressive state within the PCa tumor microenvironment and to delineate its functional impact on PCa cells.Methods:We performed clustering and annotation of single-cell RNA sequencing(scRNA-seq)data from PCa,and conducted subcluster analyses for tumor cells,T cells,and macrophages respectively.The expression changes of MYC and CD47 across tumor subtype were analyzed,and the expression variations of signal regulatory protein alpha(SIRPα)among macrophage subtype were assessed.Furthermore,we divided the PCa transcriptomic dataset samples into high-and low-MYC expression groups based on MYC expression levels,and performed differential expression analysis and enrichment analysis for each group.The functional role of MYC in PCa cells was validated using chromatin immunoprecipitation-quantitative polymerase chain reaction(ChIP-qPCR)and experimental analyses.Furthermore,animal experiments(reviewed and approved by the ethics committee of the First Affiliated Hospital of Henan University of Science and Technology,approval number:D-2025-B015)were conducted to further validate the relationship between MYC and CD47.Finally,we analyzed and validated the whey acidic protein four-disulfide core domain 2(WFDC2)+tumor subtype using transcriptomic data from PCa.Results:Through the analysis of scRNA-seq data from PCa,a total of 32,977 cells were identified,and 7 distinct cell types were annotated.The tumor cells were further divided into 10 tumor cell subtypes,among which the WFDC2+tumor cell subtype exhibited more intensive cellular communication with CD8+T cells and macrophages within the PCa tumor microenvironment.MYC and CD47 exhibited high expression levels during the middle-to-late stages of differentiation in PCa cells,whereas SIRPα maintained high expression throughout the macrophage differentiation trajectory.Enrichment analysis revealed that the WFDC2+tumor cell subtype was primarily enriched in signaling pathways such as transforming growth factor-β(TGF-β)and Wnt/β-catenin.ChIP-qPCR confirmed the regulatory relationship between MYC and CD47 expression.Additionally,it was found that MYC knockdown significantly inhibited the proliferation and invasion abilities of PCa cells,while overexpression of CD47 could reverse this effect.Animal experiment results confirmed an positive correlation between MYC and CD47 protein expression.Furthermore,Tumor Immune Dysfunction and Exclusion(TIDE)and Estimate analyses indicated that patients in the low-expression group of the WFDC2+tumor cell subtype exhibited a potentially better response to immunotherapy compared to those in the high-expression group.Conclusion:The findings of this study elucidate the role of MYC in the PCa tumor immune microenvironment.Specifically,MYC promotes the proliferation and migration of PCa cells by regulating the expression of CD47.These insights provide novel perspectives for the treatment of PCa patients.

Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.

Objective To explore the risk prediction value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging(Gd-EOB-MRI)liver imaging reporting and data system version 2018(LI-RADS v2018)with contrast-enhanced ultrasound(CEUS)LI-RADS version 2017(LI-RADS v2017)in high-risk patients with hepatocellular carcinoma(HCC).Methods The clinical and imaging data of 122 high-risk patients for HCC(with a total of 134 liver lesions)who underwent both Gd-EOB-MRI and CEUS examination at the same time and obtained pathological results within one month were retrospectively col-lected.The nodules were classified according to the CT/MRI LI-RADS v2018 and CEUS LI-RADS v2017 criteria,and the LI-RADS classification results of the two imaging methods were subjected to Cohen's Kappa test.Using pathological results as the gold stand-ard,the diagnostic efficacy of LI-RADS v2018 and LI-RADS v2017 with LR-5 as the standard for HCC was calculated separately.Results The overall consistency between the Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classification standards was good(Kappa=0.691,P＜0.001).Using LR-5 as the standard for diagnosing HCC,the sensitivity of Gd-EOB-MRI and CEUS was 84.7％and 81.2％,the specificity was 79.6％and 73.5％,the positive predictive value was 87.8％and 84.1％,the negative predictive value was 75.0％and 69.2％,and the accuracy was 82.8％and 78.4％,respectively.There was no statistically significant difference in the diagnostic efficacy of the diagnosis of HCC by LR-5 between the two imaging methods(P＞0.05).Conclusion The Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classifica-tion standards show good overall agreement.The diagnostic efficacy of Gd-EOB-MRI for HCC using LR-5 classification is better than that of CEUS.

Objective·To comprehensively evaluate the efficiency of different kits and methods for DNA and RNA extraction from blood samples.Methods·A total of 145 blood samples were collected,including those from patients with Alzheimer's disease(20 cases),fibrosis(5 cases),colorectal cancer(108 cases),and healthy individuals(12 cases).A column-based kit(Kit A)and a nucleic acid extraction instrument were used to extract genomic DNA(gDNA)from leukocytes in the blood.Cell-free DNA(cfDNA)and cell-free RNA(cfRNA)in plasma were extracted using five different kits(Kit B?F),which employed either column-based(Kit B,E)or magnetic bead-based methods(Kit C,D,F).The extraction process of Kit B was optimized by increasing the plasma sample volume and extending the elution incubation time.Furthermore,this protocol was applied to extracting cfDNA from plasma samples of 100 colorectal cancer patients.Quantitative real-time PCR(qPCR)was used to quantify the extracted DNA and RNA,and the molecular yields were compared to evaluate the extraction efficiency.A comprehensive assessment was conducted,considering factors such as cost and operation time.Results·In gDNA extraction,although the the operation time was shortened by using the nucleic acid extraction instrument,the median number of DNA molecules extracted using Kit A(column-based method)was 25.36-fold higher than that obtained with the instrument(P<0.05).For cfDNA extraction,while the overall efficiency of the three kits(Kit B?D)was similar,Kit B(column-based method)showed superior performance in low-concentration samples,with average DNA yields 4.24-fold and 1.18-fold higher than those of Kit D and Kit C(both magnetic bead-based).Optimization of Kit B's extraction protocol further improved cfDNA yield.When comparing three samples,the cfDNA yields from larger plasma input volumes was 3.98-fold,2.38-fold,and 3.82-fold higher than those from smaller input volumes,respectively.The results of cfDNA extraction from 100 colorectal cancer patients indicated that this extraction protocol reliably extracted sufficient amounts of cfDNA from clinical samples.For cfRNA extraction,Kit E(column-based method)was widely recommended due to its high efficiency,convenience,and cost-effectiveness.The median RNA content extracted using Kit E was 5.01-fold higher than that of Kit F(magnetic bead-based method).Lastly,a comparison of the copy numbers of cfDNA and cfRNA in plasma revealed that the average copy number of cfRNA per milliliter of plasma was 27.65-fold higher than that of cfDNA.Conclusion·Kit A,Kit B,and Kit E show outstanding performance in leukocyte gDNA extraction,plasma cfDNA extraction,and plasma cfRNA extraction,respectively.However,although Kit E has advantages in extraction efficiency and cost,its safety requires further evaluation.

Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective·To comprehensively evaluate the efficiency of different kits and methods for DNA and RNA extraction from blood samples.Methods·A total of 145 blood samples were collected,including those from patients with Alzheimer's disease(20 cases),fibrosis(5 cases),colorectal cancer(108 cases),and healthy individuals(12 cases).A column-based kit(Kit A)and a nucleic acid extraction instrument were used to extract genomic DNA(gDNA)from leukocytes in the blood.Cell-free DNA(cfDNA)and cell-free RNA(cfRNA)in plasma were extracted using five different kits(Kit B?F),which employed either column-based(Kit B,E)or magnetic bead-based methods(Kit C,D,F).The extraction process of Kit B was optimized by increasing the plasma sample volume and extending the elution incubation time.Furthermore,this protocol was applied to extracting cfDNA from plasma samples of 100 colorectal cancer patients.Quantitative real-time PCR(qPCR)was used to quantify the extracted DNA and RNA,and the molecular yields were compared to evaluate the extraction efficiency.A comprehensive assessment was conducted,considering factors such as cost and operation time.Results·In gDNA extraction,although the the operation time was shortened by using the nucleic acid extraction instrument,the median number of DNA molecules extracted using Kit A(column-based method)was 25.36-fold higher than that obtained with the instrument(P<0.05).For cfDNA extraction,while the overall efficiency of the three kits(Kit B?D)was similar,Kit B(column-based method)showed superior performance in low-concentration samples,with average DNA yields 4.24-fold and 1.18-fold higher than those of Kit D and Kit C(both magnetic bead-based).Optimization of Kit B's extraction protocol further improved cfDNA yield.When comparing three samples,the cfDNA yields from larger plasma input volumes was 3.98-fold,2.38-fold,and 3.82-fold higher than those from smaller input volumes,respectively.The results of cfDNA extraction from 100 colorectal cancer patients indicated that this extraction protocol reliably extracted sufficient amounts of cfDNA from clinical samples.For cfRNA extraction,Kit E(column-based method)was widely recommended due to its high efficiency,convenience,and cost-effectiveness.The median RNA content extracted using Kit E was 5.01-fold higher than that of Kit F(magnetic bead-based method).Lastly,a comparison of the copy numbers of cfDNA and cfRNA in plasma revealed that the average copy number of cfRNA per milliliter of plasma was 27.65-fold higher than that of cfDNA.Conclusion·Kit A,Kit B,and Kit E show outstanding performance in leukocyte gDNA extraction,plasma cfDNA extraction,and plasma cfRNA extraction,respectively.However,although Kit E has advantages in extraction efficiency and cost,its safety requires further evaluation.