1.A questionnaire survey and analysis on the current situation of forensic ethics practice and educational needs
Wenjie LUO ; Tiantian PAN ; Shiyue LI ; Mengjun ZHAN ; Lirong QIU ; Yuchi ZHOU ; Xin CHEN ; Fei FAN ; Zhenhua DENG
Chinese Medical Ethics 2025;38(3):378-384
ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics, with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method, basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules, but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors, but only 4.9% of them reported such violations. In terms of forensic ethics education, 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile, the respondents showed a high degree of recognition for receiving forensic ethics education, with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies, new employee training, and regular post-employment training. ConclusionCurrently, there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge, enhance ethical awareness, and improve the quality of practice.
2.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
3.Prediction of gastric cancer T staging using oral contrast-enhanced ultrasonography combined with contrast-enhanced CT
Aiqing LU ; Fei QIU ; Xin DONG ; Xiaoyan LI ; Xiuyun SUN ; Xuefeng LI ; Zhaoxin JIN ; Xiankai WANG ; Yong ZHANG
Chinese Journal of Radiological Health 2025;34(3):368-372
Objective To explore the value of oral contrast-enhanced ultrasonography (OCEUS) combined with contrast-enhanced CT in predicting preoperative T staging in patients with gastric cancer. Methods A retrospective analysis was conducted on 80 patients with gastric cancer confirmed via endoscopic biopsy or postoperative pathology at the First People’s Hospital of Jining from January 2021 to November 2024. The cohort included 56 males and 24 females, aged 38-79 years, with a median age of 55.9 years. All patients underwent both OCEUS and contrast-enhanced CT within one week prior to surgery. T staging of gastric cancer was determined using OCEUS, contrast-enhanced CT, or their combination. The results were compared with pathological T staging, and statistical differences in accuracy were analyzed. Results Pathological T staging identified T1 in 9 cases, T2 in 16 cases, T3 in 42 cases, and T4 in 13 cases. OCEUS indicated T1 in 6 cases, T2 in 14 cases, T3 in 50 cases, and T4 in 10 cases, with an accuracy rate of 80.0%. Contrast-enhanced CT indicated T1 in 4 cases, T2 in 12 cases, T3 in 52 cases, and T4 in 12 cases, with an accuracy rate of 75.0%. The combination of OCEUS and contrast-enhanced CT indicated T1 in 6 cases, T2 in 15 cases, T3 in 47 cases, and T4 in 12 cases, with an accuracy rate of 87.5%. The combined approach demonstrated significantly higher accuracy in preoperative T staging compared to either method alone (P < 0.05). Conclusion The combination of OCEUS and contrast-enhanced CT improves the accuracy of preoperative T staging in gastric cancer patients, providing valuable support for their diagnosis and treatment.
4.Chemical composition and efficacy of warming lung and resolving fluid retention of Asarum forbesii grown under different shading conditions.
Lu LIAO ; Li-Xian LU ; Hong-Zhuan SHI ; Qiao-Sheng GUO ; Cheng-Hao FEI ; Kun ZHAO ; Yuan-Yuan XING ; Yong SU ; Chang LIU ; Xin-Yue YUAN
China Journal of Chinese Materia Medica 2025;50(2):384-394
Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals
;
Mice
;
Lung/pathology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Light
;
Cytokines/genetics*
;
Humans
5.Effect of Duhuo Jisheng Decoction on knee osteoarthritis model rabbits through regulation of cell pyroptosis mediated by PI3K/Akt/mTOR signaling pathway.
Lin-Qin HE ; Peng-Fei LI ; Xiao-Dong LI ; Qi-Peng CHEN ; Zong-Han TANG ; Yu-Xin SONG ; Han-Bing SONG
China Journal of Chinese Materia Medica 2025;50(1):187-197
This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals
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Drugs, Chinese Herbal/administration & dosage*
;
Rabbits
;
TOR Serine-Threonine Kinases/genetics*
;
Osteoarthritis, Knee/genetics*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Signal Transduction/drug effects*
;
Male
;
Disease Models, Animal
;
Pyroptosis/drug effects*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Humans
;
Female
6.Preliminary application of human-computer interaction CT imaging AI recognition and positioning technology in the treatment of type C1 distal radius fractures.
Yong-Zhong CHENG ; Xiao-Dong YIN ; Fei LIU ; Xin-Heng DENG ; Chao-Lu WANG ; Shu-Ke CUI ; Yong-Yao LI ; Wei YAN
China Journal of Orthopaedics and Traumatology 2025;38(1):31-40
OBJECTIVE:
To explore the accuracy of human-computer interaction software in identifying and locating type C1 distal radius fractures.
METHODS:
Based on relevant inclusion and exclusion criteria, 14 cases of type C1 distal radius fractures between September 2023 and March 2024 were retrospectively analyzed, comprising 3 males and 11 females(aged from 27 to 82 years). The data were assigned randomized identifiers. A senior orthopedic physician reviewed the films and measured the ulnar deviation angle, radial height, palmar inclination angle, intra-articular step, and intra-articular gap for each case on the hospital's imaging system. Based on the reduction standard for distal radius fractures, cases were divided into reduction group and non-reduction group. Then, the data were sequentially imported into a human-computer interaction intelligent software, where a junior orthopedic physician analyzed the same radiological parameters, categorized cases, and measured fracture details. The categorization results from the software were consistent with manual classifications (6 reduction cases and 8 non-reduction cases). For non-reduction cases, the software performed further analyses, including bone segmentation and fracture recognition, generating 8 diagnostic reports containing fracture recognition information. For the 6 reduction cases, the senior and junior orthopedic physicians independently analyzed the data on the hospital's imaging system and the AI software, respectively. Bone segments requiring reduction were identified, verified by two senior physicians, and measured for displacement and rotation along the X (inward and outward), Z (front and back), and Y (up and down) axes. The AI software generated comprehensive diagnostic reports for these cases, which included all measurements and fracture recognition details.
RESULTS:
Both the manual and AI software methods consistently categorized the 14 cases into 6 reduction and 8 non-reduction groups, with identical data distributions. A paired sample t-test revealed no statistically significant differences (P>0.05) between the manual and software-based measurements for ulnar deviation angle, radial ulnar bone height, palmar inclination angle, intra-articular step, and joint space. In fracture recognition, the AI software correctly identified 10 C-type fractures and 4 B-type fractures. For the 6 reduction cases, a total of 24 bone fragments were analyzed across both methods. After verification, it was found that the bone fragments identified by the two methods were consistent. A paired sample t-tests revealed that the identified bone fragments and measured displacement and rotation angles along the X, Y, and Z axes were consistent between the two methods. No statistically significant differences(P>0.05) were found between manual and software measurements for these parameters.
CONCLUSION
Human-computer interaction software employing AI technology demonstrated comparable accuracy to manual measurement in identifying and locating type C1 distal radius fractures on CT imaging.
Humans
;
Male
;
Female
;
Radius Fractures/surgery*
;
Middle Aged
;
Adult
;
Aged
;
Aged, 80 and over
;
Tomography, X-Ray Computed/methods*
;
Retrospective Studies
;
Software
;
Wrist Fractures
7.Preliminary efficacy observation of 3D printed functional spinal external fixation brace combined with McKenzie therapy in the treatment of lumbar disc herniation.
Ning-Xia WANG ; Ping CHEN ; Hai-Dong WANG ; Jing JI ; Fang-Hong NIAN ; Xin LIU ; Chong-Fei JIN ; Duo-Ming ZHAO ; Hao-Lin LI ; Wei-Gang CHENG ; Gui-Lin LAI ; Guo-Biao WU
China Journal of Orthopaedics and Traumatology 2025;38(10):1047-1054
OBJECTIVE:
To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH).
METHODS:
Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment.
RESULTS:
All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05).
CONCLUSION
The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans
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Male
;
Female
;
Middle Aged
;
Printing, Three-Dimensional
;
Intervertebral Disc Displacement/surgery*
;
External Fixators
;
Lumbar Vertebrae/surgery*
;
Adult
;
Braces
;
Treatment Outcome
8.Research of injury mapping relationship of lumbar spine in reclined occupants between anthropomorphic test devices and human body model.
Yu LIU ; Jing FEI ; Xin-Ming WAN ; Pei-Feng WANG ; Zhen LI ; Xiao-Ting YANG ; Lin-Wei ZHANG ; Zhong-Hao BAI
Chinese Journal of Traumatology 2025;28(2):130-137
PURPOSE:
To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored.
METHODS:
Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1 - L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed.
RESULTS:
Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (Fz) of THOR-AV and THUMS changed in the similar trend. The maximum Fz ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (My) and the time when the maximum My occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of My measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS.
CONCLUSION
The Fz of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on Fz. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map My directly because they are very different in ATD and HBM. The My of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
Humans
;
Lumbar Vertebrae/injuries*
;
Finite Element Analysis
;
Biomechanical Phenomena
;
Manikins
;
Spinal Injuries/physiopathology*
9.Clinical Applications of Circulating Tumor DNA in Response Evaluation and Relapse Monitoring of Primary Mediastinal Large B-Cell Lymphoma.
Lu PAN ; Xin-Miao JIANG ; Yan TENG ; Ning WANG ; Ling HUANG ; Han-Guo GUO ; Si-Chu LIU ; Xiao-Juan WEI ; Fei-Li CHEN ; Zhan-Li LIANG ; Wen-Yu LI
Journal of Experimental Hematology 2025;33(2):407-415
OBJECTIVE:
To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL).
METHODS:
The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS).
RESULTS:
Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy.
CONCLUSION
CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans
;
Circulating Tumor DNA/blood*
;
Female
;
Mediastinal Neoplasms
;
Male
;
Retrospective Studies
;
High-Throughput Nucleotide Sequencing
;
Prognosis
;
Lymphoma, Large B-Cell, Diffuse/genetics*
;
Middle Aged
;
Adult
;
Aged
;
Neoplasm Recurrence, Local
;
Mutation
10.Transcriptomics and Metabolomics Analysis to Explore the Ferroptosis Susceptibility of Venetoclax-Resistant AML Cells.
Yue LI ; Jia-Qi WAN ; Xin-Tong YANG ; Bao-Quan SONG ; Fei LI ; Hong-Wei PENG
Journal of Experimental Hematology 2025;33(3):621-632
OBJECTIVE:
To investigate the susceptibility of venetoclax-resistant acute myeloid leukemia (AML) cell lines to ferroptosis and to uncover the underlying molecular mechanisms using transcriptomic and metabolomic analysis methods.
METHODS:
Venetoclax-resistant AML cell lines were constructed using a low-dose concentration escalation method. The sensitivity of cells to chemotherapeutic drugs was detected by CCK-8 assay. The susceptibility of drug-resistant cell lines to ferroptosis was assessed using transcriptomic and metabolomic analysis methods. The expression of cellular GPX4 and SLC7A11 protein was detected by Western blot, and cell death and lipid peroxidation levels were measured by flow cytometry. Depmap database and TCGA cohort were applied to explore the effect of ferroptosis-related genes expression on prognosis.
RESULTS:
Venetoclax-resistant cell lines exhibited sensitivity to ferroptosis inducers RSL3, APR246, and sorafenib. The ferroptosis inhibitor Fer-1 partially inhibited cell death induced by these inducers. Compared with the parental cells, significant changes in metabolites and gene expression levels related to ferroptosis were observed in the resistant cell lines. In particular, deregulated expression of SLC7A11 and GPX4 may play critical role in ferroptosis susceptibility. Besides, GPX4 was identified as more important for AML cell survival and higher GPX4 expression may predict shortened overall survival, NPM1 mutant and IDH1 R132 mutation positive patients may prone to possess higher GPX4 expression.
CONCLUSION
Venetoclax-resistant AML cell lines remain susceptible to ferroptosis, higher GPX4 expression maybe a critical marker for poor prognosis. Regulating the expression of ferroptosis-related genes and metabolites may enhance the efficacy of venetoclax and provide new treatment options for AML patients.
Humans
;
Ferroptosis
;
Leukemia, Myeloid, Acute/metabolism*
;
Sulfonamides/pharmacology*
;
Bridged Bicyclo Compounds, Heterocyclic/pharmacology*
;
Drug Resistance, Neoplasm
;
Metabolomics
;
Cell Line, Tumor
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Amino Acid Transport System y+/metabolism*
;
Transcriptome

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