1.Mitochondria: The Target of Ionizing Radiation Damage
Lian-Chen TIAN ; Ya-Yi YUAN ; Xu-Hong DANG
Progress in Biochemistry and Biophysics 2025;52(4):836-844
In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection.
2.Low-air-pressure clean room system: A flexible, high-quality model for assisted reproduction laboratories
Minh Tam LE ; Trung Van NGUYEN ; Thai Thanh Thi NGUYEN ; Hong Nhan Thi DANG ; Quoc Huy Vu NGUYEN
Clinical and Experimental Reproductive Medicine 2025;52(1):56-64
Objective:
This study aimed to develop a configurable clean room paradigm with low air pressure for assisted reproductive technology (ART) clinics and demonstrate the concept’s efficacy using in vitro fertilization (IVF) treatment.
Methods:
A high-standard clean room system with positive pressure (13 Pa) was built using accessible materials and equipment for ART laboratories. Methods for controlling and evaluating the clean room’s characteristics were developed and implemented for quality assessment and calibration to maximize efficiency. The feasibility of the flexible clean room concept was assessed by analyzing the key performance indicators of embryo culture and IVF treatment.
Results:
After 3 weeks of testing, the concentration of particles ≥0.5 μm was 6.04 times lower than the International Organization for Standardization (ISO) class 5 standard (3,520 particles/m3) in the IVF laboratory. Air pressure, noise, temperature, and humidity were controlled stably and appropriately. Five days after installation and handover, the volatile organic compound concentration dropped to 0.00 ppm. With blastocysts and a respectable blastocyst rate, embryonic culture with female patients younger than 40 matched the criteria (63.5% and 38.9%, respectively). After vitrified blastocysts were transferred, the pregnancy and implantation rates were 58.5% and 36.2%, respectively, demonstrating a high degree of treatment success.
Conclusion
Our customizable, high-quality, low-air-pressure clean room model can be implemented to achieve positive outcomes for infertility treatment.
3.Low-air-pressure clean room system: A flexible, high-quality model for assisted reproduction laboratories
Minh Tam LE ; Trung Van NGUYEN ; Thai Thanh Thi NGUYEN ; Hong Nhan Thi DANG ; Quoc Huy Vu NGUYEN
Clinical and Experimental Reproductive Medicine 2025;52(1):56-64
Objective:
This study aimed to develop a configurable clean room paradigm with low air pressure for assisted reproductive technology (ART) clinics and demonstrate the concept’s efficacy using in vitro fertilization (IVF) treatment.
Methods:
A high-standard clean room system with positive pressure (13 Pa) was built using accessible materials and equipment for ART laboratories. Methods for controlling and evaluating the clean room’s characteristics were developed and implemented for quality assessment and calibration to maximize efficiency. The feasibility of the flexible clean room concept was assessed by analyzing the key performance indicators of embryo culture and IVF treatment.
Results:
After 3 weeks of testing, the concentration of particles ≥0.5 μm was 6.04 times lower than the International Organization for Standardization (ISO) class 5 standard (3,520 particles/m3) in the IVF laboratory. Air pressure, noise, temperature, and humidity were controlled stably and appropriately. Five days after installation and handover, the volatile organic compound concentration dropped to 0.00 ppm. With blastocysts and a respectable blastocyst rate, embryonic culture with female patients younger than 40 matched the criteria (63.5% and 38.9%, respectively). After vitrified blastocysts were transferred, the pregnancy and implantation rates were 58.5% and 36.2%, respectively, demonstrating a high degree of treatment success.
Conclusion
Our customizable, high-quality, low-air-pressure clean room model can be implemented to achieve positive outcomes for infertility treatment.
4.Low-air-pressure clean room system: A flexible, high-quality model for assisted reproduction laboratories
Minh Tam LE ; Trung Van NGUYEN ; Thai Thanh Thi NGUYEN ; Hong Nhan Thi DANG ; Quoc Huy Vu NGUYEN
Clinical and Experimental Reproductive Medicine 2025;52(1):56-64
Objective:
This study aimed to develop a configurable clean room paradigm with low air pressure for assisted reproductive technology (ART) clinics and demonstrate the concept’s efficacy using in vitro fertilization (IVF) treatment.
Methods:
A high-standard clean room system with positive pressure (13 Pa) was built using accessible materials and equipment for ART laboratories. Methods for controlling and evaluating the clean room’s characteristics were developed and implemented for quality assessment and calibration to maximize efficiency. The feasibility of the flexible clean room concept was assessed by analyzing the key performance indicators of embryo culture and IVF treatment.
Results:
After 3 weeks of testing, the concentration of particles ≥0.5 μm was 6.04 times lower than the International Organization for Standardization (ISO) class 5 standard (3,520 particles/m3) in the IVF laboratory. Air pressure, noise, temperature, and humidity were controlled stably and appropriately. Five days after installation and handover, the volatile organic compound concentration dropped to 0.00 ppm. With blastocysts and a respectable blastocyst rate, embryonic culture with female patients younger than 40 matched the criteria (63.5% and 38.9%, respectively). After vitrified blastocysts were transferred, the pregnancy and implantation rates were 58.5% and 36.2%, respectively, demonstrating a high degree of treatment success.
Conclusion
Our customizable, high-quality, low-air-pressure clean room model can be implemented to achieve positive outcomes for infertility treatment.
5.Therapeutic effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress-induced depression and insomnia-like behavior in mice.
Hong-Bo CHENG ; Xian LIU ; Hui-Ying SHANG ; Rong GAO ; Wan-Yun DANG ; Ye-Hui GAO ; Cheng-Rong XIAO ; Yue GAO ; Zeng-Chun MA
China Journal of Chinese Materia Medica 2025;50(7):1817-1829
This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals
;
Ziziphus/chemistry*
;
Mice
;
Male
;
Depression/psychology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Sleep Initiation and Maintenance Disorders/psychology*
;
Stress, Psychological/complications*
;
Behavior, Animal/drug effects*
;
Humans
;
Disease Models, Animal
6.Mediating effect of sleep duration between depression symptoms and myopia in middle school students.
Wei DU ; Xu-Xiang YANG ; Ru-Shuang ZENG ; Chun-Yao ZHAO ; Zhi-Peng XIANG ; Yuan-Chun LI ; Jie-Song WANG ; Xiao-Hong SU ; Xiao LU ; Yu LI ; Jing WEN ; Dang HAN ; Qun DU ; Jia HE
Chinese Journal of Contemporary Pediatrics 2025;27(3):359-365
OBJECTIVES:
To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students.
METHODS:
This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia.
RESULTS:
The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081).
CONCLUSIONS
Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans
;
Myopia/etiology*
;
Male
;
Female
;
Depression/physiopathology*
;
Cross-Sectional Studies
;
Sleep
;
Adolescent
;
Students
;
Child
;
Time Factors
;
Sleep Duration
7.Multimodal image fusion-assisted endoscopic evacuation of spontaneous intracerebral hemorrhage
Chao ZHANG ; Juan LI ; Ping-Li WANG ; Hua-Yun CHEN ; Yu-Hang ZHAO ; Ning WANG ; Zhi-Tao ZHANG ; Yan-Wei DANG ; Hong-Quan WANG ; Jun WANG ; Chu-Hua FU
Chinese Journal of Traumatology 2024;27(6):340-347
Purpose::Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods.Methods::This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Nonnormally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results::A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time ( p < 0.001), less blood loss ( p < 0.001), better hematoma evacuation ( p =0.003), and a shorter stay in the intensive care unit ( p =0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group ( p =0.014). Conclusions::Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.
8.Respiratory virus infection and its influence on outcome in children with septic shock
Gang LIU ; Chenmei ZHANG ; Ying LI ; Junyi SUN ; Yibing CHENG ; Yuping CHEN ; Zhihua WANG ; Hong REN ; Chunfeng LIU ; Youpeng JIN ; Sen CHEN ; Xiaomin WANG ; Feng XU ; Xiangzhi XU ; Qiujiao ZHU ; Xiangdie WANG ; Xinhui LIU ; Yue LIU ; Yang HU ; Wei WANG ; Qi AI ; Hongxing DANG ; Hengmiao GAO ; Chaonan FAN ; Suyun QIAN
Chinese Journal of Pediatrics 2024;62(3):211-217
Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.
9.A multicenter retrospective study on clinical features and pathogenic composition of septic shock in children
Gang LIU ; Feng XU ; Hong REN ; Chenmei ZHANG ; Ying LI ; Yibing CHENG ; Yuping CHEN ; Hongnian DUAN ; Chunfeng LIU ; Youpeng JIN ; Sen CHEN ; Xiaomin WANG ; Junyi SUN ; Hongxing DANG ; Xiangzhi XU ; Qiujiao ZHU ; Xiangdie WANG ; Xinhui LIU ; Yue LIU ; Yang HU ; Wei WANG ; Qi AI ; Hengmiao GAO ; Chaonan FAN ; Suyun QIAN
Chinese Journal of Pediatrics 2024;62(11):1083-1089
Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.
10.Analysis Strategy of Deep Vein Thrombosis Metabolomic Biomarkers Based on Machine Learning Algorithms
Ming-Feng LIU ; Yan-Juan WU ; Shi-Dong ZHOU ; Li-Hong DANG ; Jian LI ; Yan DU ; Jun-Hong SUN ; Jie CAO
Chinese Journal of Analytical Chemistry 2024;52(7):1039-1049,后插1-后插4,封3
Deep vein thrombosis(DVT)is a common peripheral vascular disease in clinical practice.The lack of precise and efficient early diagnostic techniques renders it susceptible to being overlooked or misdiagnosed,and therefore,identifying trustworthy biomarkers is a major issue that has to be resolved.In this study,the endogenous metabolites in the urine of DVT rats were screened by metabolomics technology based on gas chromatograph-mass spectrometry(GC-MS)and the characteristic metabolites were identified by multiple feature selection algorithms and multivariate statistical analysis,for the development of a machine learning-based diagnostic model for DVT.The urine samples in metabolic cage in the thrombus development phase(between 48 and 72 h)of rats were collected,which was used as the models for inferior vena cava ligation.The metabolic profiles of the control group and DVT were obtained using the GC-MS method.A total of 176 kinds of endogenous metabolites were identified in rat urine through comparison with the FiehnLib database,26 kinds of differential metabolites associated with DVT were screened through a combination of the Mann-Whitney U test and orthogonal partial least squares discriminant analysis(OPLS-DA),and 13 kinds of significant metabolites strongly correlated with DVT were further evaluated in conjunction with various machine learning feature selection techniques.For DVT diagnosis,machine learning models such as Gaussian Naive Bayes(GNB),support vector machine(SVM),logistic regression(LR),and linear discriminant analysis(LDA)were developed.The diagnostic model constructed using 13 kinds of key metabolites demonstrated excellent accuracy and stability,and surpassed the predictive performance of the models utilizing 176 kinds of metabolites and 26 kinds of differential metabolites,as evidenced by examination and comparison of each model's efficacy.The study showed that the integration of multiple feature selection algorithms for analyzing metabolite information in DVT rat urine was capable of effectively identifying reliable potential markers of DVT.Furthermore,the developed machine learning model offered a novel technical approach for the automated diagnosis of DVT.

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