1.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.
2.Genomic correlates of the response to first-line PD-1 blockade plus chemotherapy in patients with advanced non-small-cell lung cancer
Tao JIANG ; Jian CHEN ; Haowei WANG ; Fengying WU ; Xiaoxia CHEN ; Chunxia SU ; Haiping ZHANG ; Fei ZHOU ; Ying YANG ; Jiao ZHANG ; Huaibo SUN ; Henghui ZHANG ; Caicun ZHOU ; Shengxiang REN
Chinese Medical Journal 2024;137(18):2213-2222
Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.
3.Characteristics of complications and impact factors of unilateral biportal endoscopy-unilateral laminectomy for bilateral decompression technique in the treatment of lumbar spinal stenosis
Jiashen SHAO ; Hai MENG ; Nan SU ; Yong YANG ; Qi FEI
International Journal of Surgery 2024;51(10):710-716
Objective:To analyze the perioperative data of patients with lumbar spinal stenosis who were surgically treated by unilateral biportal endoscopy-unilateral laminectomy for bilateral decompression (UBE-ULBD) technique, and to explore the occurrence, clinical features, and influencing factors for perioperative complications.Methods:A retrospective analysis of the clinical data of 77 patients with lumbar spinal stenosis who underwent UBE-ULBD surgery in the Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University from June 2021 to June 2023 was performed, of which 28 were males and 49 were females, with a mean age of (67.61±15.29) years. The baseline data, surgery-related information, and complications and subjective scores during the perioperative and follow-up periods of the patients were collected. Continuous variables were tested for normality using the Kolmogorov-Smirnov test. Normally distributed continuous variables were expressed as mean ± standard deviation ( ± s), and the Student- t test and analysis of variance for repeated measures information were used for comparison between groups; non-normally distributed continuous variables were expressed as median (interquartile distance) [ M( Q1, Q3)], and and non-parametric tests were used for comparison between groups. Categorical variables were expressed as number of cases and percentage, and the Chi-square test was used for comparison between groups. Variables were analyzed using univariate analysis, and indicators with statistically significant differences in the results of univariate analysis were further included in multivariate Logistic regression analysis to further clarify the independent risk factors for the occurrence of complications. Results:According to the occurrence of postoperative complications, the patients were divided into the non-complication group ( n=73) and the complication group ( n=4). The complication group included 2 cases of dural tear, 1 case of postoperative residual symptoms, and 1 case of postoperative epidural hematoma. Compared with the preoperative results, the Oswestry disability index (ODI) score and visual analogue score (VAS) for low back pain and leg pain on the first day after surgery were improved, and the differences were statistically significant ( P<0.01). Compared with the first day after surgery, except for the ODI scores, the VAS scores for low back pain and leg pain were improved at the third month after surgery, and the differences were statistically significant ( P< 0.01). The differences in intraoperative blood loss and operative time between the two groups were statistically significant ( P<0.05). The variables with statistically significant differences in univariate analysis were included in the multivariate Logistic regression analysis, and the results indicated that prolonged operative time was an independent risk factor for perioperative complications in patients ( OR=1.031, 95% CI: 1.000-1.054, P=0.030). Conclusions:As an effective minimally invasive spinal endoscopic technique for the treatment of lumbar spinal stenosis, the UBE-ULBD technique has the advantages of lower complication rates and faster postoperative recovery. Improvement of surgical proficiency by the operator and appropriate shortening of operative time can help to reduce the incidence of complications such as dural tear.
4.Effects of Tao Hong Si Wu decoction on circular RNA expression profiles in rats with middle cerebral artery occlusion
Chang-Yi FEI ; Li-Juan ZHANG ; Ni WANG ; Fu-Rui CHU ; Chao YU ; Su-Jun XUE ; Ling-Yu PAN ; Dai-Yin PENG ; Xian-Chun DUAN
Chinese Pharmacological Bulletin 2024;40(5):954-963
Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.
5.Transcatheter endocardial alginate-hydrogel implantation for the treatment of a patient with non-responsive heart failure on cardiac resynchronization therapy defibrillator:a case report
Cun-Jun ZHU ; Bo WANG ; Chao GAO ; Min SHEN ; Tao SU ; Ru-Tao WANG ; Fang-Jun MOU ; Xiao-Na CHEN ; Fei LI ; Ling TAO
Chinese Journal of Interventional Cardiology 2024;32(8):468-471
Heart failure(HF)is the end stage of almost all cardiovascular diseases,including coronary heart disease and structural heart disease.For end-stage HF,medications and cardiac assist devices have limited therapeutic effects,and heart transplantation is associated with donor shortage and immune rejection.Alginate hydrogel has the ability to mechanically support and induce cardiac tissue regeneration and repair.In March 2021,we conducted the world's first transcatheter endocardial alginate-hydrogel implantation in patients with end-stage heart failure,and explored the safety and feasibility of the treatment.Given that patients with heart failure who had undergone cardiac resynchronization therapy defibrillator(CRT-D)were excluded from previous studies,this paper is the first to report a case of transcatheter endocardial alginate-hydrogel implantation in a patient with heart failure who did not respond to CRT-D,with a significant reduction in the number of visits to the doctor and a significant improvement in the quality of life during the post-procedure follow-up,which may expand the indications for the use of this technology.
6.Extracorporeal membrane oxygenation support during transcatheter aortic valve replacement in patients with reduced left ventricular ejection fraction
Cun-Jun ZHU ; Chao GAO ; Bo WANG ; Tao SU ; Ru-Tao WANG ; Yuan HE ; Fang-Jun MOU ; Xiao-Na CHEN ; Fei LI ; Ling TAO
Chinese Journal of Interventional Cardiology 2024;32(11):642-647
Objective To evaluate the efficacy of extracorporeal membrane oxygenation(ECMO)in patients with reduced left ventricular ejection fraction(LVEF)undergoing transcatheter aortic valve implantation(TAVR).Methods This was a single-center,retrospective study enrolling a total of 30 patients with reduced LVEF undergoing TAVR from January 2020 to January 2024.Of these,12 patients underwent TAVR with ECMO.Baseline clinical characteristics,preprocedural echocardiographic and computed tomographic(CT)measurements,TAVR procedural details,and follow-up data at 60-day and 6-month were collected.Results Among the 30 patients,there were 20 males with an average age of(67.0±10.4)years,an average STS score of(8.2±1.8)points,and an average LVEF of(21.2±5.3)%.This study included 11 AR patients,all of whom were in the group without ECMO implantation,and the difference between the two groups was statistically significant(P=0.027).During the operation,there were 0 cases of circulatory collapse in the ECMO group,and 5 cases(5/18)of circulatory collapse in the non ECMO group.All 5 patients underwent emergency ECMO placement.There were statistically significant differences(P<0.05)in the comparison of two groups with circulatory collapse and salvage ECMO implantation.The technical success rate of 30 patients was 76.7%(23/30),and the instrument success rate was 60.0%(18/30).Among them,the technical success rate and instrument success rate of the ECMO group were higher than those of the non ECMO group,but the differences were not statistically significant(both P>0.05).During a 30 day follow-up,there were 0 all-cause deaths in the ECMO group and 9 all-cause deaths(9/18)in the non ECMO group.Among them,7 cases(7/18)died from cardiovascular causes.The differences in all-cause and cardiovascular cause deaths between the two groups were statistically significant(both P<0.05).During a 6-month follow-up,one patient with ECMO died due to extensive cerebral infarction.The all-cause mortality rate during the 6-month follow-up was 1/12(8.3%),while the all-cause mortality rate without ECMO was 9/18(5.0%).The difference between the two groups was statistically significant(P=0.024).The incidence of stroke with ECMO was 1/12(8.3%),while without ECMO it was 0.There was no statistically significant difference between the two groups(P=0.978).Conclusions In patients with reduced LVEF undergoing TAVR,periprocedural ECMO support does seem to improve patient outcome.
7.Hemagglutinin occlusion of needle passage for preventing complications of pulmonary puncture biopsy
Duwang QIU ; Lei ZHAO ; Lei SU ; Zhenjia LI ; Fei GAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(6):329-333
Objective To observe the value of hemagglutinin occlusion of needle passage for preventing complications of pulmonary puncture biopsy.Methods Data of 155 patients with single pulmonary nodule who underwent CT-guided percutaneous lung puncture biopsy were retrospectively analyzed.The patients were divided into observation group(n=78,injected hemagglutinin when withdrawing the needle)and control group(n=77,directly withdrawn the needle).Chest CT examination was performed immediately after completion of the procedure.Pulmonary hemorrhage grades were evaluated,and the proportions of compressed lung area were measured and compared between groups.Results Puncture and sampling were successfully performed in all 155 patients,and definite pathological diagnose was acquired in 150 cases(150/155,96.77%).High-grade hemorrhage was detected in 20 cases(20/78,25.64%)of observation group and 38 cases(38/77,49.35%)of control group,while pneumothorax was noticed in 18 cases(18/78,23.08%)with lung compression area proportion of(0[0,0])in observation group,and in 31 cases(31/77,40.26%)with lung compression area proportion of 0[0,0.76%]in control group,respectively,in observation group were better than in control group(all P<0.05).Conclusion Occlusion needle passage when withdrawing needle with hemagglutinin after pulmonary puncture biopsy could reduce the risk of hemorrhage and pneumothorax.
8.Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients
Jia-Qian XU ; Juan WANG ; Su-Ying LU ; Yan-Peng WU ; Lan-Ying GUO ; Bo-Yun SHI ; Fei-Fei SUN ; Jun-Ting HUANG ; Jia ZHU ; Zi-Jun ZHEN ; Xiao-Fei SUN ; Yi-Zhuo ZHANG
Journal of Experimental Hematology 2024;32(6):1733-1737
Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.
9.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
10.Expression level of serum UBE2C and TRIM27 in patients with endometrial cancer and their correlation with pathological parameters
Fei CHAI ; Zhenwen CHEN ; Hongyan LIU ; Su LI ; Yuanyuan GONG ; Yingying ZHAO
The Journal of Practical Medicine 2024;40(13):1808-1813
Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C(UBE2C)and tripartite motif-containing protein 27(TRIM27)in patients with endometrial cancer(EC)and their correlation with pathological parameters.Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group;65 patients with endometrial atypical hyperplasia(EAH)as EAH group,and 80 healthy subjects as the control group.Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27.The relationship between serum UBE2C,TRIM27,and pathological data was analyzed;receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC.Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects(P<0.05),and was correlated with tumor diameter,tumor differentiation,lymph node metastasis,FIGO stage,muscle layer invasion depth,cervical involvement,estrogen receptor expression,and progestogen receptor expression(P<0.05).There was positive correlation between serum UBE2C and TRIM27(r=0.475,P<0.001);and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter,lymph node metastasis,FIGO stage,and depth of musclular invasion,but negatively with tumor differentiation,estrogen receptor expression,and progestogen receptor expression(P<0.05).The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection(ZUBE2C-combination=3.406,P<0.001,ZTRIM27-combination=3.285,P=0.001).Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated,which is closely related to pathological parameters.The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.

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