1.Mechanism of post cardiac arrest syndrome based on animal models of cardiac arrest.
Halidan ABUDU ; Yiping WANG ; Kang HE ; Ziquan LIU ; Liqiong GUO ; Jinrui DONG ; Ailijiang KADEER ; Guowu XU ; Yanqing LIU ; Xiangyan MENG ; Jinxia CAI ; Yongmao LI ; Haojun FAN
Journal of Central South University(Medical Sciences) 2025;50(5):731-746
Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals
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Disease Models, Animal
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Post-Cardiac Arrest Syndrome/physiopathology*
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Heart Arrest/physiopathology*
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Humans
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Ventricular Fibrillation/complications*
2.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
3.Traditional methods and artificial intelligence: current status, challenges, and future directions of risk assessment models for patients undergoing extracorporeal membrane oxygenation.
Zhaojie LIN ; Lu LU ; Menghao FANG ; Yanqing LIU ; Jifeng XING ; Haojun FAN
Chinese Critical Care Medicine 2025;37(10):893-900
Extracorporeal membrane oxygenation (ECMO) is primarily used in clinical practice to provide continuous extracorporeal respiratory and circulatory support for patients with severe heart and lung failure, thereby sustaining life. It is a key technology for managing severe heart failure and respiratory failure that are difficult to control. With the accumulation of clinical experience in ECMO for circulatory and/or respiratory support, as well as advancements in biomedical engineering technology, more portable and stable ECMO devices have been introduced into clinical use, benefiting an increasing number of critically ill patients. Although ECMO technology has become relatively mature, the timing of ECMO initiation, management of sudden complications, and monitoring and early warning of physiological indicators are critical factors that greatly affect the therapeutic outcomes of ECMO. This article reviews traditional methods and artificial intelligence techniques used in risk assessment related to ECMO, including the latest achievements and research hotspots. Additionally, it discusses future trends in ECMO risk management, focusing on six key areas: multi-center and prospective studies, external validation and standardization of model performance, long-term prognosis considerations, integration of innovative technologies, enhancing model interpretability, and economic cost-effectiveness analysis. This provides a reference for future researchers to build models and explore new research directions.
Extracorporeal Membrane Oxygenation
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Humans
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Artificial Intelligence
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Risk Assessment
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Respiratory Insufficiency/therapy*
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Heart Failure/therapy*
4.Construction of Hsp90-based fluorescent molecular probe and evaluation of pancreatic tumor recognition effects
Haojun LUO ; Dexin KONG ; Wei HUANG ; Nan YANG ; Yanyong LIU
Basic & Clinical Medicine 2025;45(7):905-911
Objective To construct fluorescent molecular probes targeting at tumor heat shock protein 90(Hsp90)in order to enhance tumor-specific recognition.Methods The human pancreatic adenocarcinoma cell line PANC-1 and the human small cell lung cancer cell line NCI-H446 were used as the research targets to study the uptake and clearance of Cy5-P7 by tumor cells with flow cytometry as well as immune-fluorescence technology;The mechanism to mediate entrance of Cy5-P7 into the cells by Hsp90 was investigated by blocking of the PANC-1 cell surface pro-teins with monoclonal antibody to Hsp90;Human pancreatic cancer cell line PANC-1 was subcutaneously injected into posterior dorsum of BALB/c nude mice to construct a xenogeneic subcutaneous tumor model to validate the in vivo tumor recognition ability by Cy7-P7 as well as its in vivo distribution in mice.Results The uptake of Cy5-P7 by cells was significantly reduced in low temperature(P<0.05);An average fluorescence intensity in Cy5-P7-trea-ted cells was significantly reduced after blocking with a monoclonal antibody to Hsp90(P<0.05);The fluorescence intensity at the tumor site of Cy7-P7 group was higher than that of control group(P<0.05),and there was a significant presence of Cy7-P7 in the kidney and tumor fluorescence.Conclusions Cy5-P7 can effectively target at Hsp90,and its specific binding significantly enhanced the cellular uptake of Cy5-P7 fluorescent probe,which im-proved the sensitivity and accuracy of fluorescence imaging.Cy7-P7 showed good tumor active recognition in vivo,and was able to be enriched at the tumor site and metabolized out of the body in 48 h,which may effectively sup-port accurate tumor recognition.
5.Incidence of venous thromboembolism in esophageal cancer: a real-world study of 8 458 cases
Kunyi DU ; Xin NIE ; Kexun LI ; Changding LI ; Kun LIU ; Zhiyu LI ; Kunzhi LI ; Simiao LU ; Kunhan NI ; Wenwu HE ; Chenghao WANG ; Jialong LI ; Haojun LI ; Qiang ZHOU ; Kangning WANG ; Guangyuan LIU ; Wenguang XIAO ; Qiang FANG ; Qiuling SHI ; Yongtao HAN ; Lin PENG ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2024;23(1):109-113
Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
6.Identification of breast cancer and its molecular sub-types via Raman spectroscopy combined with machine learning algorithms
Juan LI ; Chao YANG ; Jiayi TANG ; Jingjing XIA ; Haojun LIU ; Ahmat ZULHUMAR· ; Xin’en CAI ; Maimaitijiang AYITILA·
International Journal of Biomedical Engineering 2024;47(3):219-226
Objective:To develop a simple, rapid, and convenient analysis method for the identification of breast cancer and its molecular sub-types.Methods:A laser confocal Raman spectrometer was used to collect Raman spectrograms of normal breast cells and different molecular sub-types of breast cancer cells, and assign the material origin of the Raman spectral peaks. First, Savitzky-Golay smoothing (with a window size of 9) was selected to perform smoothing and denoising on the Raman spectrogram. Subsequently, an iterative adaptive weighted penalty least squares method was employed for baseline correction, and principal component analysis was used to eliminate outliers. The recognition model of normal breast cells and breast cancer cells and the recognition model of different molecular sub-types of breast cancer cells were established by using three algorithms with different principles, including partial least squares discriminant analysis (PLS-DA), K-nearest neighbor (KNN), and support vector machine (SVM).Results:The Raman spectrogram and Raman peak shifts of normal breast cells and breast cancer cells were similar, but there were significant differences in intensity. The results of the machine learning models showed that the recognition accuracy of PLS-DA and SVM algorithms for distinguishing between normal breast cells and breast cancer cells was above 92.03% and 90.67%, respectively. The recognition accuracy of PLS-DA and SVM algorithms for different molecular sub-types of breast cancer cells was (83.66 ± 2.77)% and (90.55 ± 0.06)%, respectively.Conclusions:The combination of Raman spectroscopy and machine learning algorithms can achieve accurate identification of normal breast cells, breast cancer cells, and different molecular sub-types of breast cancer cells.
8.Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers
Qi SUN ; Yao FU ; Xiaobing CHEN ; Lin LI ; Hongyan WU ; Yixuan LIU ; Haojun XU ; Guoren ZHOU ; Xiangshan FAN ; Hongping XIA
Gut and Liver 2022;16(6):875-891
Background/Aims:
Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear.
Methods:
We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis.
Results:
We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively.
Conclusions
This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.
9.Clinical guideline on first aid for blast injury of the chest (2022 edition)
Zhiming SONG ; Jianming CHEN ; Jing ZHONG ; Yunfeng YI ; Lianyang ZHANG ; Jianxin JIANG ; Mao ZHANG ; Yang LI ; Guodong LIU ; Dingyuan DU ; Jiaxin MIN ; Xu WU ; Shuogui XU ; Anqiang ZHANG ; Yaoli WANG ; Hao TANG ; Qingshan GUO ; Yigang YU ; Xiangjun BAI ; Gang HUANG ; Zhiguang YANG ; Yunping ZHAO ; Sheng LIU ; Lijie TAN ; Lei TONG ; Xiaoli YUAN ; Yanmei ZHAO ; Haojun FAN
Chinese Journal of Trauma 2022;38(1):11-22
Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.
10.Thirty-six critical cases of emergency helicopter transferring between hospitals
Yi LI ; Xiaoxia LIAO ; Huimin ZHAO ; Guang ZENG ; Zhian LING ; Guojun WU ; Da LIU ; Xiaowen ZHENG ; Jianfeng ZHANG ; Haojun FAN
Chinese Critical Care Medicine 2021;33(8):1003-1006
Objective:To summarize critical cases of emergency helicopter transferring between hospitals and improve the quality and safety of critical care.Methods:The task records of Guangxi Aviation Medical Rescue Training Base from September 2017 to September 2020 were retrieved. The mission acceptance, implementation results, disease spectrum composition, pre-transfer preparation and medical intervention on board were summarized.Results:① General information: a total of 168 patients of helicopter transfer requests were registered, of which 36 patients were transferred, 35 patients were successful, 1 patient had cardiac arrest during the landing phase, and died several hours after continuous resuscitation. Of the 36 patients 30 were males and 6 were females, with median age of 50.5 (29.8, 66.0) years old, the average transfer time was (54.95±17.89) minutes, and the average transfer distance was (205.74±74.68) km. ② Disease spectrum included 11 cases of stroke (30.55%), 7 cases of trauma (19.45%), 5 cases of severe pneumonia (13.89%), 5 cases of heart and macro-vascular diseases (13.89%), 5 cases of abdominal emergency (13.89%), and 3 other conditions (8.33%).③ Severity: 31 patients (86.11%) were severe (≥15) according to acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score; 19 patients (52.78%) were high-risk emergency transport (≥6) according to Hamilton early warning score (HEWS); 6 patients (85.71% of trauma patients) were severe trauma (≥16) according to injury severity score (ISS). ④ Preparation before transfer: remote consultation was carried out to evaluate the latest state of the patient's condition, especially the respiratory and circulatory conditions. Relevant items were reviewed and emergency treatments were implemented when necessary. Targeted preparation was made for accidents that might occur during transfer, such as electrocardiogram (94.44%), blood gas analysis (94.44%), brain CT (36.11%) and other auxiliary examinations, endotracheal intubation or tracheotomy (72.22%), deep vein catheterization (91.67%), placement of gastric tube (86.11%) and urinary tube (88.89%), adjustment of sedative (38.89%), vasoactive drugs (58.33%) and drugs for dehydration and lowering intracranial pressure (33.33%), and fixation of fracture (11.11%), etc. ⑤ On-board medical intervention: cardiac monitoring, blood pressure, respiration and blood oxygen monitoring were carried out in all patients. The parameters of patients using ventilator were adjusted in time (66.67%). The dosage of patients using micropump was adjusted in time (91.67%). Other aspects included the use of sedative and analgesics (38.89%), sputum suction nursing (75.00%), all kinds of catheter nursing (endotracheal intubation/incision nursing of 72.22%, indwelling catheter nursing of 88.89%), and cardiopulmonary resuscitation for patient with cardiac arrest (2.78%).Conclusion:As the patients transferred by helicopter are mainly those of critically ill at this stage, the requirements for airborne medical equipment and rescue technology are high, and there is an urgent need to establish technical specifications and personnel training standards.

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