1.Visualization Analysis of Research Hotspots and Trends in Field of Tumor Therapy Based on CiteSpace and VOSviewer
Yuhang FANG ; Chuchu ZHANG ; Bailu SUI ; Yan WANG ; Runxi WANG ; Yu CHEN ; Xinhe YUAN ; Hongjun YANG ; Ying ZHANG
Cancer Research on Prevention and Treatment 2025;52(4):297-304
Objective To explore the research hotspots and development trends in the field of cancer treatment in the past decade. Methods The CNKI and Web of Science Core Collection databases were searched for Chinese and English articles related to cancer treatment published over the last 10 years. Bibliometric research methods were employed, including keyword cluster analysis of published literature. Results A total of 45 455 Chinese articles and 866 958 English articles were retrieved. Combining the visualization analysis results and the current research dilemma of tumor treatment revealed that the current research hotspots of tumor treatment domestically and internationally can primarily focus on four key areas. In the realm of targeted therapy, efforts are directed towards the discovery of new drug targets, overcoming resistance to targeted therapy, and the development of monoclonal antibodies and antibody–drug conjugates. In the field of immunotherapy, the emphasis lies in enhancing the response rate to immune checkpoint inhibitors, determining the mechanisms behind resistance to immunotherapy, and improving the safety of treatment. The research in traditional Chinese medicine (TCM) covers evidence-based evaluation studies on TCM treatment, the identification of populations that can gain the most benefit from TCM, and strategies for improving the quality of life. In the area of novel drug development, cutting-edge technologies, such as organoid-based screening for anticancer drugs, synthetic biology, and artificial intelligence, are under investigation. Conclusion New targeted drugs, immune efficacy improvement, multidisciplinary integration, nano-delivery, and TCM innovation are the key research directions in the field of tumor therapy in the future.
2.Study on the stability of PBMCs recovered from leukocyte-depleted filter residues
Ju LIN ; Zhiqiang XIANG ; Dongfen DU ; Fang YUAN ; Miaoyu WANG ; Yue WU ; Kaiyu HUANG ; Lieyong SANG
Chinese Journal of Blood Transfusion 2025;38(5):723-733
Objective: To identify an optimal back-flush solution for leukocyte-depleted filters that maximizes peripheral blood mononuclear cell (PBMC) recovery with high viability, long-term storage stability, and sterility of the harvested residues, thereby providing a clinically translatable strategy. Methods: Three sterile bag-packaged solutions—Saline, Solvent, and Hanks' balanced salt solution (HBSS)—were used to back-flush randomly assigned leukocyte-depleted filters. Nucleated cell recovery rate and viability of the harvested residues were compared. The optimal solution identified was applied to an expanded sample set. PBMC viability and yield were evaluated after 1h vs 48h storage of the residues. PBMCs isolated from the residues were cryopreserved in liquid nitrogen for 1 month, followed by post-thaw comparisons of viability and T-cell expansion capacity. Results: The Solvent group achieved the highest and most consistent nucleated cell recovery rate. Post-flush recovery rate from filters after 400 mL whole blood processing was (21.3±1.6)% for the Solvent group, significantly higher than Saline group (19.2±6.3)% and HBSS group (11.2±5.0)%, with residues from all groups maintaining viability >90%. No biologically significant difference in residue viability was observed between 48h vs 1h storage groups (93.3±2.3)% vs (95.7±1.8)%). PBMC recovery rates from residues showed no statistical difference between 48h vs 1h storage groups [(48.2%±9.5%)vs (40.41%±8.35%), P>0.05], with (17.7±2.6)×10
cells. After 1-month cryopreservation and 10-day expansion, PBMCs isolated from 48-hour-stored residues retained (91.2±3.2)% viability and achieved a (61.9±15.9)-fold expansion. Conclusion: The bag-packaged Solvent, as a back-flush solution, enables sterile acquisition of leukocyte-depleted filter residues through closed-system tubing connections. These residues maintained PBMC viability and recovery rates after 48h storage at 2℃-8℃, with post-cryopreservation (1-month liquid nitrogen) viability and expansion capacity remaining stable. This protocol complies with blood bank regulatory criteria, addresses the concerns about the infectious window period in cell therapy raw materials, and provides a clinically translatable strategy for PBMC-based applications.
3.Genetic Association Between Attention-Deficit/Hyperactivity Disorder and Sarcopenia: A Bidirectional Two-Sample, Two-Step Mendelian Randomized Study
Xiaoyan ZHAO ; Yueqin JIN ; Leping MA ; Xiaole ZHAO ; Xiaoqing FANG ; Fenfang YUAN
Psychiatry Investigation 2025;22(3):304-310
Objective:
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia.
Methods:
In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method.
Results:
Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences.
Conclusion
The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.
4.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
Purpose:
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.
Methods:
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results:
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
5.Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration
Jiyeon OCK ; Guo Nan YIN ; Fang-Yuan LIU ; Yan HUANG ; Fitri Rahma FRIDAYANA ; Minh Nhat VO ; Ji-Kan RYU
Investigative and Clinical Urology 2025;66(1):74-86
Purpose:
To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED).
Materials and Methods:
Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure.These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays.
Results:
Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression.
Conclusions
Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.
6.Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation
Yuan YIN ; Jing HE ; Yu FANG ; Min WEI ; Wang ZHANG
Biomolecules & Therapeutics 2025;33(3):529-543
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.
7.Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation
Yuan YIN ; Jing HE ; Yu FANG ; Min WEI ; Wang ZHANG
Biomolecules & Therapeutics 2025;33(3):529-543
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.
8.Genetic Association Between Attention-Deficit/Hyperactivity Disorder and Sarcopenia: A Bidirectional Two-Sample, Two-Step Mendelian Randomized Study
Xiaoyan ZHAO ; Yueqin JIN ; Leping MA ; Xiaole ZHAO ; Xiaoqing FANG ; Fenfang YUAN
Psychiatry Investigation 2025;22(3):304-310
Objective:
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia.
Methods:
In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method.
Results:
Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences.
Conclusion
The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.
9.Genetic Association Between Attention-Deficit/Hyperactivity Disorder and Sarcopenia: A Bidirectional Two-Sample, Two-Step Mendelian Randomized Study
Xiaoyan ZHAO ; Yueqin JIN ; Leping MA ; Xiaole ZHAO ; Xiaoqing FANG ; Fenfang YUAN
Psychiatry Investigation 2025;22(3):304-310
Objective:
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia.
Methods:
In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method.
Results:
Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences.
Conclusion
The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.
10.Establishment and stress analysis of a finite element model for adolescent cervical disc herniation
Yuxin ZHAO ; Liang LIANG ; Feng JIN ; Yangyang XU ; Zhijie KANG ; Yuan FANG ; Yujie HE ; Xing WANG ; Haiyan WANG ; Xiaohe LI
Chinese Journal of Tissue Engineering Research 2025;29(3):448-454
BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

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