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.A quantitative research on China's basic medical insurance policy text for Traditional Chinese Medicine from the perspective of policy instrument
Sheng-Hui SHI ; Mao YOU ; Rui-Feng LI ; Xue-Qing TIAN ; Ping REN ; Lan-Tao WU ; Qiu-Ying ZHENG
Chinese Journal of Health Policy 2024;17(4):16-22
Objective:To summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.
3.Clinical and imaging analysis of COVID-19-related osmotic demyelination syndrome
Yuyue QIU ; Chenhui MAO ; Jialu BAO ; Li SHANG ; Tianyi WANG ; Bo LI ; Yixuan HUANG ; Yuhan JIANG ; Shanshan CHU ; Wei JIN ; Liling DONG ; Feng FENG ; Jing GAO
Chinese Journal of Neurology 2024;57(7):763-769
Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.
4.Case analysis of brain abscesses caused by Nocardia asiatica: A case report
WU Hai-feng ; WU Qiu-ping ; ZHOU Gui-zhong ; HUANG Mao-yi ; LI Wen-ting
China Tropical Medicine 2023;23(6):667-
Abstract: Objective To investigate the clinical characteristics and diagnosis key points of brain abscess caused by Nocardia asiatica, and provide a clinical basis for diagnosing and treating intracranial infection caused by Nocardia. Methods A case of pulmonary Nocardia asiatica complicated with brain abscess diagnosed at the Second Affiliated Hospital of Hainan Medical University was selected to analyze the clinical manifestations, cerebrospinal fluid characteristics, pulmonary and cranial imaging features, and treatment plan, and to summarize the diagnosis and treatment experience. Results The patient was an elderly woman with a history of diabetes, dry cough was the first symptom without fever or headache. At the beginning of the course, it was diagnosed as pulmonary infection and tuberculosis in the local hospital, and received conventional antimicrobial and anti-tuberculosis therapies, but showed no improvement. The patient developed progressive limb weakness, followed by consciousness disorders, and coma. Cerebrospinal fluid (CSF) adenosine deaminase and lactate dehydrogenase were not abnormal, CSF pressure, protein and white blood cells were high, mainly with multiple nuclear cells. CSF glucose and chloride were normal in the early stage of the disease, but decreased significantly in the later stage. Metagenomic analysis of cerebrospinal fluid indicated Nocardia asiatica with a specific sequence number of 537. Lung CT showed exudation, abscess, and cavity in the right lung. Skull MRI scan + enhancement suggested multiple scattered abscesses in both cerebral hemispheres. The abscesses were of different sizes and showed ring enhancement, with extensive surrounding edema, and ventricular compression. After treatment with meropenem, linezolid, and compound sulfamethoxazole tablets, the cerebrospinal fluid recovered, and the lesions in the lungs and intracranial structures improved. Conclusions Brain abscess caused by Nocardia asiatica is similar to the tuberculous brain in clinical symptoms, cerebrospinal fluid examination, craniocerebral imaging, so we should be alert to the possibility of Nocardia infection in patients with diabetes. At the same time, metagenomic testing of the cerebrospinal fluid can help confirm the diagnosis. The mortality and disability rates of brain abscess caused by Nocardia are high. Early diagnosis and treatment can improve the prognosis.
5.Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.
Yi-Lun QU ; Zhe-Yi DONG ; Hai-Mei CHENG ; Qian LIU ; Qian WANG ; Hong-Tao YANG ; Yong-Hui MAO ; Ji-Jun LI ; Hong-Fang LIU ; Yan-Qiu GENG ; Wen HUANG ; Wen-Hu LIU ; Hui-di XIE ; Fei PENG ; Shuang LI ; Shuang-Shuang JIANG ; Wei-Zhen LI ; Shu-Wei DUAN ; Zhe FENG ; Wei-Guang ZHANG ; Yu-Ning LIU ; Jin-Zhou TIAN ; Xiang-Mei CHEN
Chinese journal of integrative medicine 2023;29(4):308-315
OBJECTIVE:
To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.
METHODS:
Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.
RESULTS:
Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.
CONCLUSIONS
Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans
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Male
;
Diabetes Mellitus, Type 2
;
Diabetic Nephropathies
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Hyperuricemia
;
Kidney
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Proteinuria
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Renal Insufficiency, Chronic/complications*
7.Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules.
Cheng-Feng WU ; Jia-Bao LIAO ; Dan LI ; Mao-Lin YANG ; Qiu-Zhen CHEN ; Zhong-Qi YANG
China Journal of Chinese Materia Medica 2023;48(15):4231-4236
Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.
Humans
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Medicine, Chinese Traditional/adverse effects*
;
Drugs, Chinese Herbal/adverse effects*
;
Prospective Studies
;
Drug-Related Side Effects and Adverse Reactions/epidemiology*
;
China
8.Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway.
Fang-Ting ZHOU ; Ying ZONG ; Wu-Qiong HOU ; Sen-Sen LI ; Fei YANG ; Li-Ting XU ; Xia MAO ; Yu-Dong LIU ; Xiao-Hui SU ; Hong-Ye WAN ; Jing-Feng OUYANG ; Qiu-Yan GUO ; Wei-Jie LI ; Zhen WANG ; Chao WANG ; Na LIN
China Journal of Chinese Materia Medica 2023;48(23):6457-6474
The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats
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Mice
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Animals
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Chronic Pain/metabolism*
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Rats, Sprague-Dawley
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Ganglia, Spinal/metabolism*
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Ligands
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Signal Transduction
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Hyperalgesia/metabolism*
;
Drugs, Chinese Herbal
9.Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men.
Xi Jia TANG ; Lei Jing DUAN ; Wen Li LIANG ; Si CHENG ; Ting Li DONG ; Zhen XIE ; Kang Mai LIU ; Fei YU ; Zi Huang CHEN ; Guo Dong MI ; Liang LIANG ; Hong Jing YAN ; Lin CHEN ; Li LIN ; Dian Min KANG ; Xiao Bing FU ; Mao Feng QIU ; Zhen JIANG ; Jie XU ; Zun You WU
Chinese Journal of Epidemiology 2022;43(1):72-77
Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies
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HIV Infections/epidemiology*
;
HIV-1
;
Homosexuality, Male
;
Humans
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Immunoenzyme Techniques
;
Incidence
;
Male
;
Sexual and Gender Minorities
10.Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China.
Ran ZHANG ; Ting Li DONG ; Wen Li LIANG ; Zhao Bing CAO ; Zhen XIE ; Kang Mai LIU ; Fei YU ; Geng Feng FU ; Yu Qi ZHANG ; Guo Yong WANG ; Qiao Qin MA ; Shao Bin WU ; Yan LI ; Wei DONG ; Zhen JIANG ; Jie XU ; Zun You WU ; Jun YAO ; Pin Liang PAN ; Mao Feng QIU
Chinese Journal of Epidemiology 2022;43(4):523-527
Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology*
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Cities
;
Drug Resistance
;
Drug Resistance, Viral/genetics*
;
Female
;
Genotype
;
HIV Infections/epidemiology*
;
HIV Seropositivity/drug therapy*
;
HIV-1/genetics*
;
Homosexuality, Male
;
Humans
;
Male
;
Phylogeny
;
Reverse Transcriptase Inhibitors/therapeutic use*
;
Sexual and Gender Minorities

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