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.Effect of obesity on displacement of left-sided double-lumen tube during positional changes
Aimin FENG ; Yingshuai QIAO ; Zhen ZHANG ; Xihua LU
Chinese Journal of Anesthesiology 2024;44(7):802-805
Objective:To evaluate the effect of obesity on the displacement of a left-sided double-lumen tube (DLT) during positional changes.Methods:This was a prospective cohort study. Six hundred and two patients who underwent elective chest surgery and required insertion of a left-sided DLT from February 2020 to November 2023 in our hospital were selected and divided into 2 groups based on the body mass index (BMI): obesity group (BMI≥28 kg/m 2,n=208) and non-obesity group (18.5 kg/m 2≤BMI<28 kg/m 2,n=394). General characteristics of patients, history of chest surgery, DLT model, depth of DLT placement in supine position, height/depth of placement (H/D) ratio, and distance of DLT displacement were recorded. DLT displacement was defined as a displacement distance of ≥15 mm. The logistic regression was used for analysis of the relationship between BMI and left DLT shift during positional changes. The receiver operating characteristic curve was used to evaluate the accuracy of BMI in predicting the left-sided DLT displacement during positional changes. Results:Compared with non-obese group, the depth of DLT placement was significantly reduced, the H/D ratio was increased, the distance of DLT displacement was increased, and the incidence of DLT displacement was increased in obese group ( P<0.05). The results of binary logistic regression analysis showed that a BMI≥28 kg/m 2 was an independent risk factor for DLT displacement ( OR value [95% confidence interval]=4.18 (2.36-7.38), P<0.001). The sensitivity of BMI in predicting the left-sided DLT displacement during positional changes was 77.4%, and the specificity was 69.6%, with an optimal cutoff value of 27.48 kg/m 2 and an area under the receiver operating characteristic curve of 0.757. Conclusions:Obesity can increase the probability of the left-sided DLT displacement during positional changes.
3.Comparison of effects of left paratracheal pressure and cricoid pressure during mask ventilation in obese patients
Aimin FENG ; Yingshuai QIAO ; Zhen ZHANG ; Xihua LU
Chinese Journal of Anesthesiology 2024;44(10):1182-1185
Objective:To compare the effects of left paratracheal pressure (LPP) and cricoid pressure (CP) during mask ventilation in obese patients.Methods:Sixty patients of either sex, aged 18-60 yr, with 28 kg/m 2≤body mass index<35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: LPP group and CP group. In LPP group, pressure was applied beside the trachea, above the clavicle towards the vertebral direction, while in CP group, pressure was applied downwards to the cricoid cartilage, with a force of pressure between 25-35 N. The spatial relationship between the esophagus, trachea, and cricoid cartilage, the presence of air shadows in the gastric antrum during mask ventilation, and the cross-sectional area (CSA) of the gastric antrum before and after mask ventilation as well as the airway pressure during mask ventilation were observed. Results:In both groups, the esophagus was located in the left of the trachea in the supraclavicular region. There were no statistically significant differences in the airway pressure during mask ventilation and the CSA of the gastric antrum prior to mask ventilation between the two groups ( P>0.05). Compared to LPP group, the proportion of patients with air shadows in the gastric antrum during mask ventilation was significantly increased, and the CSA of the gastric antrum was increased after mask ventilation in CP group ( P<0.05). Conclusions:Compared to CP, LPP can decrease the development of air entering the stomach during mask ventilation and reduce the CSA of the gastric antrum after mask ventilation in obese patients.
4.Genetic and clinical characteristics of 26 cases with glycogen storage disease type Ⅲ
Xueyuan ZHANG ; Ping ZHANG ; Jiayan FENG ; Xihua LI ; Yi LU ; Xinbao XIE ; Jianshe WANG
Chinese Journal of Hepatology 2024;32(11):1005-1012
Objective:To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results:Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G>T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P=0.031) and ALT ( P=0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P>0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P<0.05) and with advancing age, increased ALT diminished while CK level elevated ( P<0.05). Conclusions:The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.
5.Platelet transfusion practice and related outcomes in patients with veno-arterial extracorporeal membrane oxygenation: a three-year retrospective study
Yi ZHU ; Xufeng CHEN ; Jinsong ZHANG ; Yong MEI ; Jinru LV ; Gang ZHANG ; Deliang HU ; Wei LI ; Huazhong ZHANG ; Feng SUN ; Juan WU ; Yongxia GAO ; Xihua HUANG ; Hui ZHANG
Chinese Journal of Emergency Medicine 2021;30(10):1177-1181
Objective:To study the application of blood products in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and evaluate its effect on the prognosis.Methods:A total of 83 adult patients treated with VA-ECMO in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to January 2020 were grouped by survival to explore the risk factors of 28-day mortality using binary logistic regression, and the threshold was calculated by ROC curve.Results:Platelet transfusion ( OR=2.506, 95% CI: 1.142-5.499) and non-myocarditis disease ( OR=6.881, 95% CI: 1.615-29.316) were the risk factors of 28-day mortality in adult VA-ECMO patients. The threshold of platelet transfusion was 0.427 mL/(kg·d) (sensitivity 78.4%, specificity 69.6% , AUC 0.735). Conclusions:The increased platelet transfusion is related to the poor prognosis of adult patients with VA-ECMO. Refractory myocarditis patients are better treated with VA-ECMO.
6.Analysis of early volume balance and prognosis of severe cardiogenic shock patients treated with veno-arterial extracorporeal membrane oxygenation
Feng SUN ; Xufeng CHEN ; Jinsong ZHANG ; Yong MEI ; Jinru LV ; Wei LI ; Deliang HU ; Gang ZHANG ; Huazhong ZHANG ; Yuan GUO ; Juan WU ; Yongxia GAO ; Xihua HUANG ; Hui ZHANG
Chinese Journal of Emergency Medicine 2021;30(10):1182-1186
Objective:To analyze the early volume characteristics of patients with severe cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and the relationship between their early volume and the prognosis.Methods:This study reviewed patients of Emergency Medical University , treated with VA-ECMO and screened the patients with severe cardiogenic shock and VA-ECMO running more than 72 h for further study. The basic condition of the patients was recorded, and the fluid balance in the first 72 h was analyzed. The patients were grouped according to their fluid balance in the first 72 h. The gender, age, survival rate, continuous renal replacement therapy (CRRT) rate, intra-aortic balloon pump (IABP) rate, and invasive mechanical ventilation rate were compared between the two groups, and the relative risk to the prognosis was calculated. The prognosis was compared between the two groups. Results:Totally 77 patients with severe cardiogenic shock were enrolled. Forty-one cases survived, with an overall survival rate of 53.2%. The volume balance at 48-72 h and the total volume balance at the first 72 h were different between the survival and dead groups. Compared with the positive balance group, patients in the negative balance group were less likely to receive CRRT or invasive mechanical ventilation during the first 72 h. Patients in the negative balance group during the first 72 h had a better survival rate, and their relative risk of survival was 1.81 (95% confidence interval: 1.101, 2.985). However, there was no significant difference in survival rate according to every 24 h fluid balance.Conclusions:Patients with severe cardiogenic shock treated with VA-ECMO who had negative total volume balance during the first 72 h are more likely to survive and less likely to require CRRT or invasive mechanical ventilation.
7.Retrospective analysis of clinical characteristics of 78 patients receiving extracorporeal cardiopulmonary resuscitation
Wei LI ; Jinsong ZHANG ; Xufeng CHEN ; Yong MEI ; Jinru LV ; Deliang HU ; Feng SUN ; Gang ZHANG ; Huazhong ZHANG ; Xihua HUANG ; Hui ZHANG ; Weiwei WANG
Chinese Journal of Emergency Medicine 2021;30(10):1187-1191
Objective:To summarize the clinical characteristics and influencing factors on clinical outcome of patients receiving extracorporeal cardiopulmonary resuscitation (ECPR).Methods:A total of 78 patients receiving ECPR admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People’s Hospital) from March 2015 to December 2020 were retrospectively enrolled. Patients were divided into the survival group and death group according to clinical outcome. Their baseline data, CPR associated parameters, and pre-ECPR laboratory tests were compared between the two groups.Results:Of the 78 included patients, 51 patients were male and 27 female. Twenty-three patients finally survived, including 10 males and 13 females. There were no significant differences in age, body mass index and underlying diseases (hypertension, diabetes and coronary heart disease) between the two groups (all P > 0.05). The proportion of male patients in the survival group was lower than that in the death group ( P=0.017). Meanwhile Survival After Veno-Arterial ECMO (SAVE) score was significantly higher in the survival group than that in the death group[ (-1.57±4.15) vs. (-9.36±5.36), P<0.001]. The proportion of by-stander CPR in the survival group was higher than that in the death group ( P=0.014). The pre-ECPR serum AST, ALT, and Cr levels in the survival group were significantly lower than those in the death group (all P<0.05). Logistic regression analysis showed that by-stander CPR ( OR=0.114, 95% CI: 0.015~0.867, P=0.036) and SAVE score ( OR=0.625, 95% CI: 0.479~0.815, P=0.001) were independent risk factors predicting ICU death in patients receiving ECPR. Conclusions:ECPR is an efficient tool to improve clinical outcomes of patients with cardiac arrest. By-stander CPR and SAVE score are independent risk factors predicting ICU death in patients receiving ECPR.
8.The clinical experience of emergency medical team-initiated inter-hospital transport on extracorporeal membrane oxygenation
Yong MEI ; Jinsong ZHANG ; Xufeng CHEN ; Jinru LV ; Deliang HU ; Gang ZHANG ; Wei LI ; Huazhong ZHANG ; Feng SUN ; Xihua HUANG ; Hui ZHANG ; Yongxia GAO
Chinese Journal of Emergency Medicine 2020;29(2):227-230
Objective:To summarize the inter-hospital transport experience on extracorporeal membrane oxygenation (ECMO) led by a team from emergency department.Methods:The clinical data of 21 patients transferred under the support of ECMO between December 2016 and February 2019 were retrospectively analyzed. All patients were transferred to the First Affiliated Hospital of Nanjing Medical University from other hospitals. Interhospital distance, transport methods, patient demorgraphic characteristics, disease diagnosis, intubation location, intubation method, adverse events during transport and transport outcome were retrieved.Results:Eighteen of the 21 patients were transferred under our mobile ECMO team from outer hospitals to our ECMO intensive care unit. Three patients were cannulated by physicians of outer hospital and transported to our ECMO intensive care unit. All patients were transported by ground ambulance, and the distances varied from 2.5 to 252 km, with an average distance of 112.3±103.2 km. No death occurred during transportation. Adverse events in transport occurred in 6 patients. Of these, the most common were patient-related adverse events..Conclusions:Inter-hospital transport by ECMO in China is currently dominated by ground ambulance.. Experienced mobile ECMO team can safely operate inter-hospital transport supported by ECMO
9.Predictive factors of renal replacement therapy in patients with extracorporeal membrane oxygenation
Huazhong ZHANG ; Xufeng CHEN ; Jinsong ZHANG ; Yong MEI ; Jinru LV ; Deliang HU ; Gang ZHANG ; Wei LI ; Feng SUN ; Yuan GUO ; Jinxia CAI ; Xihua HUANG ; Hui ZHANG ; Weiwei WANG
Chinese Journal of Emergency Medicine 2020;29(2):222-226
Objective:To explore the predictive factors of renal replacement therapy (RRT) in extracorporeal membrane oxygenation (ECMO) patients.Methods:The clinical data of 68 ECMO patients treated at Emergence Department of Jiangsu Provincial Hospital from January 2015 to December 2018 were retrospectively analyzed. Vasoactive-inotropic score (VIS) was used to assess the usage of vasoactive-inotropic drugs on day 1, 2 and 3 of ECMO (24 h VIS, 48 h VIS, and 72 h VIS). According to received RRT or not, patients were divided into the RRT group and non-RRT group. Age, gender, weight, VIS, presence of cardiac arrest before ECMO, ECMO mode, and ECMO treatment time were compared. Logistic regression analysis was used to identify predictive factors for RRT in ECMO patients.Results:Of the enrolled patients, 73.5% of ECMO patients received RRT. The mean age, 24 h VIS, ECMO failure and mortality of the RRT group were significantly higher than those of the non-RRT group ( P <0.05). The use of RRT was 87.8% in elderly ECMO patients (> cutoff age of 38.5 years). According to the cutoff value of 24 h VIS (33.75), ECMO patients were divided into the high VIS group and low VIS group. The rates of RRT and mortality were both exceeded 90% in the high VIS group, which was significantly higher than that of the low VIS group ( P <0.05). Logistic regression analysis showed that age ( OR=1.223) and 24 h VIS ( OR=1.033) were predictive factors of RRT in ECMO patients ( P <0.05). Conclusions:Age and 24 h VIS show the predictive value for RRT in ECMO patients.
10.Clinical study of extracorporeal membrane oxygenation and left ventricular function in patients with acute fulminant myocarditis
Zhongman ZHANG ; Xufeng CHEN ; Jinsong ZHANG ; Yong MEI ; Jinru LV ; Deliang HU ; Gang ZHANG ; Wei LI ; Huazhong ZHANG ; Feng SUN ; Juan WU ; Yongxia GAO ; Xihua HUANG ; Hui ZHANG
Chinese Journal of Emergency Medicine 2020;29(2):213-216
Objective:To evaluate left ventricular systolic function (LVEF) after extracorporeal membrane oxygenation (ECMO) in patients with acute fulminant myocarditis (AFM).Methods:Seven patients were admitted in the First Affiliated Hospital of Nanjing Medical University from August 2018 to November 2018. All the patients accepted veno-arterial extracorporeal membrane oxygenation (V-AECMO). Complications associated with ECMO and clinical outcome were documented. Transthoracic echocardiography (TTE), single photo emission computed tomography (SPECT), and cardiac magnetic resonance (CMR)were performed to evaluate LVEF.Results:Seven patients were successfully weaned from V-AECMO, 2 of whom had oxygenator leakage, 4 had femoral artery bleeding after decannulation, and 2 had femoral artery pesudoaneurysm. There was no statistical difference in LVEF evaluation between TTE and CMR [(62.4±6.8)% vs (58.9±8.2)%, P >0.05]. CMR and SPECT further revealed myocardial pathological change and coronary arterial blood perfusion. Conclusions:ECMO is recommended in patients with AFM. TTE is simple and easy to perform and is not inferior to CMR in LVEF evaluation. CMR can reflect pathological changes of cardiomyocytes at the cellular level, and SPECT can reflect coronary perfusion.

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