BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the etiology and treatment of dysuria shortly after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH), so as to improve the therapeutic efficacy. Methods A retrospective analysis was conducted on 1361 BPH patients who received HoLEP at our hospital during Mar. 2018 and Mar. 2025. All patients underwent ultrasound, computed tomography (CT), urethral probing or radiography, cystourethroscopy, and urodynamic testing. The causes, treatments and prognosis of dysuria after operation were summarized. Results ninety-eight patients (7.2%) experienced dysuria within 3 months after surgery, and all patients received initial urethral dilation. Among the 62 cases with urethral stricture, 28 were treated with urethral dilation (average of 8 sessions), 16 underwent external urethral incision, 8 underwent anterior urethroplasty, and 10 underwent transurethral plasma incision for urethral stricture. Of the 12 cases with residual prostate tissue, 5 underwent urethral plasma prostatectomy and 7 received medication. All of the 12 cases with bladder neck contracture underwent transurethral plasma incision of the bladder neck and local drug injection. Five cases with intravesical blood clots underwent urethral blood clot irrigation, 2 of which developed active bleeding and then underwent electrocoagulation. Four cases with detrusor dysfunction had catheters re-indwelled for one week followed by medication. Two cases with stone and one case with tissue fragment impacted in the urethra underwent urethral holmium lithotripsy and cystoscopic removal. All patients underwent reoperation successfully and experienced complete resolution or significant improvement of urinary difficulties. Conclusion A certain proportion of patients experience dysuria after HoLEP, with diverse etiologies. The combination of prevention and treatment can reduce the incidence of dysuria.

The field of post-marketing benefit-risk assessment for traditional Chinese medicine（TCM） is still in its nascent stage， lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM， and explored the critical techniques and specific implementation steps involved in the assessment process. Initially， appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently， key technologies were outlined， including the establishment of a benefit-risk indicator system， the assignment of indicator weights， and the definition of criteria attributes. Furthermore， the implementation steps were elaborated， which involved defining decision-making issues， data collection， evaluation methodologies， variability factors， and sensitivity analysis. Finally， a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.

OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams