Objective: To explore whether the long-term and frequent use of citrate anticoagulants negatively affects the bone metabolism balance of female frequent plateletpheresis donors, so as to better protect their health. Methods: A total of 65 female plateletpheresis donors and 55 female whole-blood donors from Guangzhou Blood Center (May to December 2024) were enrolled as experimental and control groups respectively, stratified into age subgroups (18-39 years and 40-60 years). Serum levels of 25-hydroxyvitamin D [25(OH)D], procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and type I collagen carboxy-terminal telopeptide (CTX) were measured. Differences in bone metabolism markers between experimental and control groups across age subgroups were compared. ANOVA was used to analyze dose-response relationships between donation age, annual apheresis donation frequency, and biochemical indicators. Results: In the 40-60 age subgroup, 25(OH)D levels were significantly lower in the experimental group (P<0.05), exhibiting a linear increase with age and a linear decrease with annual donation frequency. No significant differences in CTX or PINP levels were observed between experimental and control groups in either age subgroup. Conclusion: High-frequency plateletpheresis donation does not disrupt bone metabolic balance in female donors. However, it is associated with reduced vitamin D levels in female donors aged >40 years, potentially increasing the risk of osteoporosis. Vitamin D supplementation is recommended for high-frequency female plateletpheresis donors in this age group.

Immunotherapy represents the third revolution in the pharmacological treatment of tumors and has demonstrated considerable efficacy in the management of malignant solid tumors, including melanoma and lung cancer. By contrast, breast cancer is frequently categorized as a “cold tumor” because of its limited immunogenicity and immunoreactivity, which hinder research progress and clinical outcomes in immunotherapy. Only a small proportion of patients derive benefits from immunotherapeutic interventions, and the development of drug resistance remains a concern. In this regard, novel strategies should be explored for converting immunologically inert “cold tumors” into immunologically active “hot tumors”, thereby expanding the population that will benefit from breast cancer immunotherapy. This study reviews new strategies to transform breast cancer from “cold tumor” to “hot tumor”. Strategies include enhancing the expression of tumor antigens, promoting immune infiltration, and reversing the immunosuppressive microenvironment. Results also emphasize the importance of comprehensive treatment to enhance systemic immunity.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

Objective To investigate the temporal and spatial relationship between autophagosome formation during spermatid deformation and lipid droplet distribution in seminiferous tubules,thereby providing insights into the en-ergy sources underlying spermiogenesis.Methods Healthy adult wild-type male mice were used in this study.The expression profile of the autophagy marker microtubule-associated protein light chain 3(LC3)in the testis was ex-amined using immunohistochemical staining and Western blot.The ultrastructural features of autophagosomes were observed via transmission electron microscopy.Lipid droplets in the seminiferous tubules were visualized by Oil Red O staining,and the relationship between lipid metabolism and energy dynamics was assessed by measuring ATP content and ATPase activity.Results Autophagosomes were detected in deforming spermatids and Sertoli cells.LC3 was predominantly expressed in the cytoplasm of elongating spermatids,with increasing levels found from stages Ⅱ to Ⅳ.Concurrently,lipid droplets within these cells also increased,peaking in spermatids and residual bodies during stagesⅦ-Ⅷ,followed by a decline.In contrast,lipid droplets in Sertoli cells remained markedly in-creased during stages Ⅸ-Ⅰ and low during stages Ⅱ-Ⅷ.The change of ATP levels in the seminiferous tubules showed a similar pattern as Sertoli cell lipid content,whereas ATPase activity showed an inverse trend.All these changes displayed a clear stage-dependent manner.Conclusions During spermatid elongation in mice LC3 expres-sion,autophagosome formation,lipid droplet accumulation in both spermatozoa and Sertoli cells,as well as ATP and ATPase levels in seminiferous tubules exhibit a tightly coordinated spatiotemporal relationship.These findings suggest that autophagy and lipid metabolism synergistically contribute to the energy supply required for the extensive cellular remodeling that occurs during spermiogenesis.

Objective To explore the effects of behavior change intervention based on the multi-ple-theory model on patients with dyslipidemic ischemic stroke.Methods A total of 93 patients with dyslipidemic ischemic stroke who were hospitalized in the vascular neurology ward of Beijing Tiantan Hospital,Capital Medical University from January to August 2024 were selected as the study subjects using the convenience sampling method.They were randomly divided into control group(n=49)and intervention group(n=44)using the envelope-drawing method.Patients in the control group re-ceived routine stroke health education,while those in the intervention group underwent a 3-month be-havior change program guided by the multiple-theory model.The levels of healthy behaviors,body mass index(BMI),total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL-C),and low-density lipoprotein(LDL-C)were compared between the two groups.Results There were no statistically significant differences in general information and disease-related data between the two groups(P＞0.05).At 1-,3-,and 6-month after the intervention,the level of healthy behaviors in the intervention group was higher than that in the control group,with statistically significant differ-ences(P＜0.05).There was a statistically significant difference in BMI between the two groups at 6 months after the intervention(P＜0.05).The TC levels in the intervention group at 3 and 6 months after the intervention were lower than those in the control group,with statistically significant differences(P＜0.05).The HDL-C level in the intervention group at 6 months after the intervention was high-er than that in the control group,with a statistically significant difference(P＜0.05).The LDL-C levels in the intervention group at 1-,3-,and 6-month after the intervention were lower than those in the control group,with statistically significant differences(P＜0.05).There were no statistically significant differences in TG levels between the intervention group and the control group at different time points after the intervention(P＞0.05).Conclusion The behavior change intervention pro-gram based on the multiple-theory model can effectively improve and maintain healthy behaviors and improve blood lipid levels in patients with dyslipidemic ischemic stroke.

Objective To utilize single-cell and peripheral blood transcriptomic data from 3D brain organoids,combined with machine learning,to analyze the role of mitochondrial autophagy genes in schizophrenia(SCZ).Methods By integrating two machine learning algorithms,we identified differentially expressed mitochondrial autophagy-related genes between schizophrenia patients and healthy controls using peripheral blood RNA sequencing data.The relationship between mitophagy gene,immune cells and inflammatory factors was further explored.Comprehensive single-cell analysis was used to explore the signaling pathways and specific transcription factors based on mitophagy genes.Results Using machine learning,seven key mitophagy genes expressed in schizophrenia patients were identified.Based on Mitoscore analysis,at the single-cell level,neurons with high mitochondrial autophagy activity(Mitohigh_Neuron)formed new interactions with endothelial cells via the SPP1 signaling pathway.Conclusion This study identified two subtypes of mitophagy and seven key mitophagy genes in schizophrenia,providing new insights into the pathogenesis of the disease.

Objective To analyze the epidemiological distribution of new occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Guangxi Zhuang Autonomous Region from 2013 to 2022. Methods Data of newly diagnosed pneumoconiosis cases reported in Guangxi Zhuang Autonomous Region from 2013 to 2022 were collected, and epidemiological characteristics were analyzed using descriptive analysis method. Results A total of 972 newly diagnosed pneumoconiosis cases were reported in Guangxi Zhuang Autonomous Region from 2013 to 2022. Except for mica pneumoconiosis, 12 other types of pneumoconiosis were reported. Most of the cases were males, accounting for 97.0%. The diagnosis age of the cases of 40-<60 years old accounted for 77.4%, and the dust exposure age<30 years of the cases accounted for 96.4%. Silicosis was the most common type of pneumoconiosis, followed by coal workers' pneumoconiosis, accounting for 64.6% and 27.9%, respectively. The cases of stage Ⅰ, Ⅱ and Ⅲ pneumoconiosis accounted for 77.7%, 14.9% and 7.4%, respectively. The regional distribution was mostly in Hechi City, accounting for 51.9%. Industry distribution was more common in non-ferrous metal mining, coal mining and washing industry, accounting for 64.9% in total. Most cases were reported in private enterprises and small to medium-sized enterprises, accounting for 53.7% and 76.6% respectively. The most common occupations were coal miners and drillers, accounting for 47.7% in total. Conclusion Newly diagnosed pneumoconiosis cases in Guangxi Zhuang Autonomous Region show certain clustering characteristics in terms of disease type, region, enterprise characteristics, and occupation distribution. The prevention and treatment of pneumoconiosis in small and medium-sized private enterprises in key areas and key industries should be strengthened, especially for workers over 40 years old and with less than 30 years of dust exposure.