1.Mechanisms and Molecular Networks of Hypoxia-regulated Tumor Cell Dormancy
Mao ZHAO ; Jin-Qiu FENG ; Ze-Qi GAO ; Ping WANG ; Jia FU
Progress in Biochemistry and Biophysics 2025;52(9):2267-2279
Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.
2.Variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip
Xu-Dong LUO ; Xin-Rong LI ; Cheng-Yi LI ; Peng QI ; Ting-Ting LIANG ; Shu-Bin LIU ; Zheng-Ze QIANG ; Jun-Gang HE ; Xu LI ; Xiao-Cheng WEI ; Xiao-Li FENG ; Ming-Wei WANG
Chinese Traditional Patent Medicine 2024;46(3):747-754
AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.
3.Determination of rifapentine concentration in human serum by two-dimensional liquid chromatography
Tao KE ; Tian HE ; Pei-Ze ZHANG ; Wei LI ; Yang ZHOU ; Feng WANG ; Miao-Na LIU
The Chinese Journal of Clinical Pharmacology 2024;40(11):1638-1641
Objective To develop a two-dimensional liquid chromatographic method for rifapentine blood concentration determination.Methods The blood concentration of rifapentine was determined by a novel two-dimensional liquid chromatography(2D-LC)with a one-dimensional column:Aston SC2T(3.5 mm ×50.0 mm,5 μm);a two-dimensional column:Aston SCB(4.6 mm ×250.0 mm,5 μm);the temperature of the column was 40 ℃;the flow rate was 1.0 mL·min-1;the detection wavelength was 335 nm;the injection volume was 300 μL.The specificity,standard curve and lower limit of quantification,precision and recovery,and stability of the method were investigated.The method was used to determine the blood concentration of rifapentine in tuberculosis patients.Results Rifapentine showed good linearity within 0.33-18.62 μg·mL-1 with the standard curve equation of y=2.68 x 105x-5 850.36(r=0.997),the recoveries were 99.81%-105.08%,and the intra-and inter-day precision were ≤4.84%.The results of rifapentine blood concentration measurements in tuberculosis patients were in the range of 0.10-54.70μg·mL-1,and 64.74%were within the therapeutic window concentration range(8-30 μg·mL-1).Conclusion The method is easy to operate,has high sensitivity,low detection limit and high specificity,and is suitable for clinical blood concentration determination.Individual differences in the administration of rifapentine in tuberculosis patients are large,and blood concentration monitoring is required for individualized treatment.
4.Analysis of FU Wen-Bin's Experience in the Treatment of Radiation Encephalopathy
Jin-Feng GAO ; Shan-Ze WANG ; Ying DENG ; Xi-Chang HUANG ; Si-Bo WEI ; Wen-Bin FU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1493-1498
Based on the principle of'treating disease and seeking the root cause',Professor FU Wen-Bin proposed'treating radiation encephalopathy(REP)from yang',pointing out that the main pathogenesis of REP is yang qi deficiency,brain spirit dystrophy,phlegm and blood stasis blocking orifices.Using'supplementing yang and unblocking yang simultaneously','treating spirit from heart and gallbladder',combined with the method of regulating spirit and unblocking orifices at acupoints of governor vessol and conception vessel,and using the integrated acupuncture mode of'firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation'to play the role of supporting yang and treating spirit can effectively relieve symptoms and delay the development of the disease.
5.Analysis of prognostic factors in patients with resectable gastric cancer with vascular cancer thrombus
Ze-Feng YANG ; Xiang-Yu CHENG ; Hong-Mei YU ; Yu-Sheng WANG
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(2):151-157
Objective To explore the factors influencing the prognosis of patients with Resectable gastric adenocarcinoma with vascular cancer thrombus(RGAVCT)and to develop a relevant columnar graphic prognostic model.Methods Clinicopathologic data of 530 patients with gastric adenocarcinoma combined with vascular cancer embolization who underwent radical gastrectomy for gastric cancer at the Affiliated Cancer Hospital of Shanxi Medical University were retrospectively collected from January 2017 to January 2022,and were randomly assigned to the training cohort and the validation cohort in a 7∶3 ratio.Kaplan-Meier curves and Log-rank test and multifactorial Cox regression were used to analyze the risk factors for death in the training cohort patients,and to construct Nomogram Model for the probability of survival at 1,2,and 4 years in RGAVCT patients.ROC curves were used to analyze the efficacy of the Nomogram model in the training cohort and validation cohort patients.Results Age,postoperative chemotherapy,tumor size,Ki67 expression status,T-stage,N-stage,and clinical stage of patients in the training cohort were the influencing factors on survival(OS)of patients with RGAVCT(P<0.05);postoperative chemotherapy(P<0.001,HR=0.302,95%CI:0.219-0.418),T-stage[T3(P=0.015,HR=11.782,95%CI:1.628-85.283),T4a+4b(P=0.005,HR=17.219,95%CI:2.343-126.559)],N staging[N2(P=0.309,HR=1.310,95%CI:0.779-2.201)N3a(P=0.001,HR=2.268,95%CI:1.407-3.657),N3b(P<0.001,HR=2.836,95%CI:1.708-4.709)]were independent influences on OS in patients with RGAVCT.Cox regression results were used to develop nomogram models for predicting the probability of patients'survival at 1,2,and 4 years after surgery.The AUROC area and C index were>0.7 for the training cohort and>0.67 for the validation cohort.Conclusion In this study,we developed a nomogram model of 1-,2-,and 4-year postoperative survival probabilities of RGAVCT patients,which can better predict the postoperative survival of RGAVCT patients.
6.Advances in actuation technology of wearable exoskeletons
Yi-Fei PENG ; Hua-Jun WANG ; Ze-Feng WANG ; PEYRODIE LAURENT ; Zhao ZHANG ; Xia HAN
Chinese Medical Equipment Journal 2024;45(4):104-110
The research status of the actuation technology of wearable exoskeletons was introduced.Kinds of actuation technologies and actuators were analyzed in terms of advantage,disadvantage and applicable scenario.It's pointed out the actuation technology of wearable exoskeletons should be oriented to high-performance micro-motors,new actuators,actuation modularity and intellectualization.[Chinese Medical Equipment Journal,2024,45(4):104-110]
7.Maintenance and improvement program for WYD2000 field surgical lamp
Ming-Ming ZHU ; Ji-Su CAO ; Ze-Rui ZHANG ; Jiang-Hui HAO ; Rui-Zhe WANG ; Feng ZHOU ; Lu-Chuan XUN
Chinese Medical Equipment Journal 2024;45(4):116-118
The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]
8.Research status of hand rehabilitation robots
Ge-Ge ZHANG ; Lian-Xin HU ; Ze-Feng WANG ; Shi-Jia HU ; Dan WANG ; Xin-Xin NI ; Hua-Jun WANG ; Shan-Qi GU
Chinese Medical Equipment Journal 2024;45(11):88-96
The current research status of different structures,driving modes and training modes of hand rehabilitation robots at home and abroad was introduced.The disadvantages of the existing hand rehabilitation robots were analyzed.It's pointed out hand rehabilitation robots in the future would involve in the combination of rigid and flexible wearing,new intelligent driving mode and multi-mode rehabilitation training.[Chinese Medical Equipment Journal,2024,45(11):88-96]
9.Clinical Results of Implantation of Subcutaneous Implantable Cardioverter Defibrillator After Transvenous Lead Extraction
Cuizhen YUAN ; Feng ZE ; Ding LI ; Jiangbo DUAN ; Cuncao WU ; Jinshan HE ; Xu ZHOU ; Long WANG ; Xuebin LI
Chinese Circulation Journal 2024;39(8):781-784
Objectives:To evaluate the safety and efficacy of implantation of subcutaneous implantable cardioverter defibrillator(S-ICD)after transvenous lead extraction(TLE)in ICD patients without pacing indications. Methods:All patients who underwent TLE at Peking University People's Hospital from June 2018 to October 2023 were consecutively included.TLE indication,S-ICD implantation indication,defibrillation threshold(DFT)test,complications and postoperative follow-up were collected and analyzed. Results:A total of 11 patients with TV-ICD underwent S-ICD implantation after TLE,eight patients were males and median age were 56(44,65)years.The indications for TLE were infection and lead dysfunction.Nine patients were implanted with S-ICD for secondary prevention,and the most common cause of implantation was ion channelopathies(5 cases).The operative time for S-ICD was 51(48,58)minutes and no perioperative complications were noted.Eight patients underwent DFT testing,and 100%were successful.During a median follow up of 30(9,39)months,a total of six appropriate treatments occurred in two patients,and no complications occurred,including inappropriate treatment,ineffective treatment,infection,lead malfunction and death. Conclusions:Our study provides evidence for S-ICD implantation as a replacement after TV-ICD removal.The S-ICD implantation after TLE is safe and effective.
10.Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction.
Lin YAO ; Yan-Ze LIU ; Meng-Yuan LI ; Zi-Yang ZHANG ; Shuo YU ; Shu-Nan SUN ; Ming XU ; Hai-Zhu ZHENG ; Shi-Qi MA ; Zhen ZHONG ; Hong-Feng WANG
Chinese Acupuncture & Moxibustion 2023;43(12):1343-1350
OBJECTIVES:
To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy.
METHODS:
Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined;with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm.
RESULTS:
Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039).
CONCLUSIONS
Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Humans
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Electroacupuncture
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Acupuncture Therapy
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Acupuncture Points
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Diabetes Mellitus, Type 2/therapy*
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Glycated Hemoglobin
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Cognitive Dysfunction/therapy*
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Cholesterol
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gamma-Aminobutyric Acid

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