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.Analysis of the timeliness of anti-retroviral therapy among newly reported HIV/AIDS cases
SU Dehua ; CHEN Xiangyang ; LI Jun ; ZHAO Lina ; ZHANG Hemei ; ZHU Tingting ; HU Wenxue ; LAI Jiangyi
Journal of Preventive Medicine 2025;37(8):804-808
Objective:
To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases.
Methods:
Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model.
Results:
A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases.
Conclusion
From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.
3.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.
4.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.
5.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.
6.Comparison of patient trust patterns between tertiary hospitals and primary healthcare institutions:A mixed research based on interviews and survey experiment
Xi-Yang TONG ; Hong-Yu LI ; Jun SU ; Jin-Xin ZHANG ; Shi-Chao ZHAO ; Xiao-Jie SUN
Chinese Journal of Health Policy 2024;17(4):38-44
Objective:This study utilizes a hybrid research design,integrating interviews with experimental surveys,to investigate the variances in patient trust models between tertiary hospitals and primary healthcare institutions.Methods:Thirty-eight residents participated in semi-structured interviews,which were then analyzed using content analysis.The experimental survey segment divided participants into two groups:"Tertiary Hospitals"and"Primary Healthcare Institutions,"resulting in 648 valid questionnaires.These questionnaires were subjected to variance analysis to assess differences.Results:Patients exhibit greater systemic trust in tertiary hospitals than in primary healthcare facilities,while interpersonal trust is stronger in primary healthcare settings.Suggestions:Therefore,strategies should be developed to bolster systemic trust at the primary level and emphasize the advantages of interpersonal trust.Moreover,specific measures are required to reshape patients'interpersonal trust in tertiary hospitals.
7.Causal association between depression and stress urinary incontinence:A two-sample bidirectional Mendelian randomization study
Cheng-Xiao JIANG ; Wei-Qi YIN ; Jing-Jing XU ; Ying-Jiao SHI ; Li WANG ; Zhi-Bo ZHENG ; Rui SU ; Qin-Bo HU ; Jun-Hai QIAN ; Shu-Ben SUN
National Journal of Andrology 2024;30(3):217-223
Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.
8.Simultaneou determination of twenty-eight constituents in Dayuan Drink by UPLC-MS/MS
Yu-Jie HOU ; Xin-Jun ZHANG ; Ming SU ; Xin-Rui LI ; Yue-Cheng LIU ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Kang-Ning XIAO ; Long-Yun DUAN ; Lei CAO ; Zhen-Yu XUAN ; Shan-Xin LIU
Chinese Traditional Patent Medicine 2024;46(11):3545-3552
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.
9.Real-world meta-analysis of the safety of domestically produced rotavirus vaccine
Feng SU ; Yunzhi SHI ; Min XU ; Mu LI ; Jun CHEN ; Yifei HUO ; Yifeng CHEN ; Jie ZHAO ; Jinfeng SU
Chinese Journal of Microbiology and Immunology 2024;44(5):431-440
Objective:To evaluate the real-world safety of the domestic rotavirus attenuated live vaccine in China.Methods:Studies on the incidence of adverse event following immunization (AEFI) published from January 1, 2020 to July 31, 2023 were retrieved from National Knowledge Infrastructure (CNKI), CQVIP, Wanfang Database, PubMed, Medline, and Embase. Surveillance data about AEFI reports related to the domestic rotavirus vaccine rotavirus were collected. A meta-analysis on the safety of the rotavirus vaccine after vaccination was conducted using R software, and subgroup analyses were conducted on the incidence of AEFI in different regions and time periods.Results:A total of 36 articles were included involving 25.332 million doses of vaccine. The incidence of AEFI associated with the domestic rotavirus vaccine was 19/100 000 doses [95%CI: 15/100 000-24/100 000 doses]; the incidence was 26/100 000 doses [95%CI: 17/100 000-39/100 000 doses] in the northern regions and 16/100 000 doses [95%CI: 11/100 000-23/100 000 doses] in the southern regions; it was 24/100 000 doses [95%CI: 12/100 000-45/100 000 doses] before 2017 and 27/100 000 doses [95%CI: 18/100 000-39/100 000 doses] after 2017.Conclusions:The incidence of AEFI related to the domestic rotavirus vaccine is within the expected range, and the safety of the vaccine is good based on the real-world data.
10.Efficacy analysis of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori in Ningxia
Chengcheng FENG ; Linke MA ; Jun LIU ; Xue LI ; Xiaoming SU ; Yuanyuan TANG ; Xiaofei LI ; Yanling LI ; Qiang WEI ; Zhanbin HOU ; Xilong ZHANG ; Shengjuan HU
Chinese Journal of Digestion 2024;44(5):302-307
Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.


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