1.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
2.Phase Change and Quantity-quality Transfer Analysis of Medicinal Materials, Decoction Pieces and Standard Decoction of Haliotidis Concha (Haliotis discus hannai)
Zhihan YANG ; Jingwei ZHOU ; Weichao WANG ; Yu HUANG ; Chuang LUO ; Lian YANG ; Chenyu ZHONG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):206-214
ObjectiveTo explore the quantity-quality transfer process of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(Haliotis discus hannai) by analyzing the physical phase and compositional changes, so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha(H. discus hannai) from different habitats were collected and prepared into corresponding calcined products and standard decoction, and the content of CaCO3 of the three samples were determined and the extract yield and transfer rate of CaCO3 were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry(XRF), X-ray diffraction(XRD) was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry(FTIR) was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram, while combining hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) to find the common and differential characteristics, in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha(H. discus hannai). ResultsThe CaCO3 contents of the 20 batches of medicinal materials, decoction pieces and standard decoction of Haliotidis Concha(H. discus hannai) were 93.87%-98.95%, 96.02%-99.97% and 38.29%-51.96%, respectively, and the extract yield of standard decoction was 1.71%-2.37%, and the CaCO3 transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity, and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction, the difference in the relative contents was obvious, which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO3 of aragonite and calcite, while calcined Haliotidis Concha only contained CaCO3 of calcite, and standard decoction mainly contained CaCO3 of calcite and Na2CO3 of natrite. FTIR results showed that there were internal vibrations of O-H, C-H, C=O, HCO3- and CO32- groups in Haliotidis Concha, while O-H, HCO3- and CO32- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO3 content, the transformation of CaCO3 aragonite crystal form to calcite crystal form and the absence of organic components after calcination, and the changes of calcined products and standard decoction are mainly the decrease of CaCO3 content and the increase of Na2CO3 relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction, which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.
3.Rapid Analysis of Cyanide Based on a Ratiometric Fluorescent Probe Using Gold Nanoclusters-Fluorescein
Tai-Shen HE ; Zhong-Jiang LÜ ; Yi-Ming SUN ; Yu-Yang LI ; Yi YE ; Yao LIN ; Lin-Chuan LIAO
Journal of Forensic Medicine 2025;41(4):340-347
Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.
4.Risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrillation after percuta-neous left atrial appendage closure combined with radiofrequency ablation
Xiu-tian SU ; Hua WANG ; Guang-qiang WANG ; Ting YU ; Meng-meng REN ; Lin ZHONG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):162-167
Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60% vs.37.20%),old myocardial infarction(OMI)(11.50%vs.1.70%)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P<0.05 or<0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95%CI 1.772~43.069,P=0.008)and LAD(OR=1.053,95%CI 1.006~1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95%CI 0.593~0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95%CI 0.477~0.620)and LAD(AUC=0.602,95%CI 0.531~0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.
5.Analysis of transurethral water vapor thermal therapy for the treatment of benign prostatic hyperplasia
Ming-yang PANG ; Yong WEI ; Jian-zhong LIN ; Jun WANG ; Ming-yu LIU ; Fu-yang LIU ; Yi-bo MA ; Tong ZHAO ; Qing-yi ZHU
National Journal of Andrology 2025;31(7):603-607
Objective:To investigate the efficacy and safety of transurethral water vapor thermal therapy(WVTT)using the Rezūm system for benign prostatic hyperplasia(BPH)in the real world.Methods:A total of 181 patients with BPH were recruited from the Second Affiliated Hospital of Nanjing Medical University from August 2022 to December 2023,of whom 173 patients were treated with WVTT using the Rezūm system,while 8 patients were treated with WVTT combined with TURP.They were followed up at 1,3,and 6 months postoperatively to assess changes in the IPSS,QoL,Qmax,IIEF-5,and the occurrence of any complications.Results:All 181 surgeries in this group were successfully completed.The operation time of the Rezūm system was(4.6±1.4)mi-nutes.The postoperative indwelling catheterization time was(8.0±2.1)days.With a follow-up of at least 6 months,there was a significant decrease in PV,IPSS and QoL,and a remarkable increase had been found in Qmax as well(P<0.05).There was no sig-nificant difference in IIEF-5 before and after the operation(P>0.05).In this groups of patients,postoperative complications mainly included 95 cases(52.5%)of gross hematuria,6 cases(3.3%)of retrograde ejaculation,5 cases(2.8%)of urethral stricture,4 cases(2.2%)of prostatitis,and 10 cases(5.5%)of urinary tract infection.Four cases(2.2%)underwent surgical retreatment for BPH after surgery.Conclusion:In the real world,the use of Rezūm thermal steam ablation system for the treatment of BPH has sat-isfactory short-term effect,short surgical time,and significant improvement in IPSS,QoL,Qmax,which does not adversely affect sexu-al function.
6.Mental health literacy and its relationship with symptoms of depression,anxiety,and insomnia in young adults
Yuqing YANG ; Jing HUANG ; Zixin LIN ; Tong YU ; Xiyuan CHEN ; Ning YANG ; Shaoling ZHONG ; Liang ZHOU
Chinese Mental Health Journal 2025;39(4):344-349
Objective:To explore the level of mental health literacy and its relationship with symptoms of de-pression,anxiety,and insomnia in young adults.Methods:A total of 10 273 young adults aged 18-23 in Guang-zhou were selected and assessed with the National Mental Health Literacy Questionnaire,Patient Health Question-naire-9(PHQ-9),General Anxiety Disorder 7-Item Scale(GAD-7)and Insomnia Severity Index(ISI).Results:Totally 1 137(11.1%)participants met the criteria for adequate mental health literacy,2 758(26.8%)participants were with symptoms of depression,1 355(13.2%)with symptoms of anxiety and 4 936(48.0%)experiencing symptoms of insomnia.Logistic regression analyses showed that after adjusting for other factors,substandard mental health literacy was an independent risk factor for symptoms of depression,anxiety and insomnia(OR=2.08,1.93,1.49;95%CI:1.74-2.48,1.52-2.46,1.31-1.70).Conclusion:The level of mental health literacy in young a-dults is insufficient,and the lack of mental health literacy is significantly associated with the symptoms of depres-sion,anxiety and insomnia.
7.Analysis of clinical characteristics and prognosis of congenital chylothorax in neonates
Ying CHENG ; Yanfen PENG ; Junjian LYU ; Wei ZHONG ; Jiakang YU ; Tulian LIN ; Qiuming HE
Chinese Journal of Applied Clinical Pediatrics 2025;40(2):105-108
Objective:To summarize the clinical characteristics of congenital chylothorax (CC) in neonates, and to analyze the effects of conservative treatment and the prognosis.Methods:A case control study was conducted.Clinical data of neonates with CC treated in the Department of Neonatal Surgical Intensive Care Unit, Guangzhou Women and Children′s Medical Center Guangzhou Medical University, from January 2015 to April 2023 were collected.The patients were divided into a survival group and a death group according to the outcome.SPSS 26.0 software was used for statistical analysis, and binary Logistic regression was used for the analysis of risk factors for death.Results:A total of 55 patients were included in this study, including 35 males and 20 females.The gestational age at birth and birth weight were 37.1 (34.7, 38.7) weeks and 3 250 (2 640, 3 540) g, respectively.Among the patients included, 30 cases had bilateral pleural effusion, 25 cases had unilateral pleural effusion, and 22 cases had hydrops fetalis; 50 cases were prenatally diagnosed with pleural effusion, with the mean gestational age at diagnosis being 31.0(26.0, 34.6) weeks.Additionally, 21 cases had polyhydramnios, and 18 cases had mediastinal displacement.Ten cases received intrauterine treatment and 17 cases were treated with octreotide.The maximum daily amount of pleural effusion was 31.7(12.0, 62.5) mL/kg, and pleural effusion resolved within 14 (6, 22) days.The length of hospital stay was 23 (12, 36) days.Forty-four cases survived, while 11 cases died.The differences in polyhydramnios, gestational age, bilateral pleural effusion, hydrops fetalis and Apgar score were significant between the survival and death groups (all P<0.05).Binary Logistic regression analysis revealed that bilateral pleural effusion and a low 5-minute Apgar score were independent risk factors for early death in neonates with CC (all P<0.05).A total of 38 children were followed up at the age of 2.30 (1.24, 3.46) years.There was 1 case of recurrence, and none of the patients experienced recurrent respiratory infections. Conclusions:CC is most common in full-term infants and has a predominantly bilateral effusion, its long-term prognosis with conservative treatment is promising.However, neonates with CC who present with bilateral pleural effusion or low 5-minute Apgar scores have an increased risk of early mortality.
8.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
9.Analysis of Hormone Levels in Patients with Hematological Diseases Before and After Hematopoietic Stem Cell Tansplantation.
Fen LI ; Yu-Jin LI ; Jie ZHAO ; Zhi-Xiang LU ; Xiao-Li GAO ; Hai-Tao HE ; Xue-Zhong GU ; Feng-Yu CHEN ; Hui-Yuan LI ; Qi SA ; Lin ZHANG ; Peng HU
Journal of Experimental Hematology 2025;33(5):1443-1452
OBJECTIVE:
By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage.
METHODS:
The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed.
RESULTS:
After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same.
CONCLUSION
HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans
;
Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Hematologic Diseases/blood*
;
Follicle Stimulating Hormone/blood*
;
Triiodothyronine/blood*
;
Luteinizing Hormone/blood*
;
Thyroid Gland/metabolism*
;
Estradiol/blood*
;
Thyrotropin/blood*
;
Gonads/metabolism*
;
Adult
;
Middle Aged
;
Adrenocorticotropic Hormone/blood*
;
Hormones/metabolism*
;
Adrenal Cortex/metabolism*
;
Prolactin
10.A small molecule cryptotanshinone induces non-enzymatic NQO1-dependent necrosis in cancer cells through the JNK1/2/Iron/PARP/calcium pathway.
Ying HOU ; Bingling ZHONG ; Lin ZHAO ; Heng WANG ; Yanyan ZHU ; Xianzhe WANG ; Haoyi ZHENG ; Jie YU ; Guokai LIU ; Xin WANG ; Jose M MARTIN-GARCIA ; Xiuping CHEN
Acta Pharmaceutica Sinica B 2025;15(2):991-1006
Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1+) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1+ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca2+, and depletion of ATP and NAD+. Furthermore, CTS selectively suppressed tumor growth in the NQO1+ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD+/Ca2+ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

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