1.Application status of the model organism zebrafish in radiation medicine research
Juancong DONG ; Jingjie WANG ; Jinhuan YU ; Jiao CHENG ; Xuhong DANG ; Guodong YANG
Acta Laboratorium Animalis Scientia Sinica 2025;33(1):141-148
As a model organism that bridges the gap between cells and traditional mammals,the zebrafish has broad application prospects in radiation medicine research.Among its unique advantages are its characteristics of a high homology with human genes,high fertility,short embryonic period,and transparent and easy to observe embryos,making it an important tool in radiation medicine research.Recently,remarkable progress has been made in the application of zebrafish to investigate low-dose radiation biological effects,radiation therapy,and radiation damage prevention and treatment,key areas of radiation medicine.In this paper,these applications are reviewed;we explore the value of zebrafish in radiation medicine research and provide a reference for experimental research in related fields.
2.Mechanism of Chonghe paste promoting wound healing of diabetic ulcer through PINK1/parkin pathway-mediated mitophagy
Ying DANG ; Yuqi JIAO ; Ri HAI ; Jianping SHI
Chinese Journal of Pathophysiology 2025;41(2):338-347
AIM:To explore the mechanism of Chonghe paste in regulating PTEN-induced kinase 1(PINK1)/parkin pathway-mediated mitophagy on diabetic ulcer wound healing.METHODS:Thirty-six rats were used to construct a diabetic ulcer model by high-sugar and high-fat feed,intraperitoneal injection of streptozotocin and skin defect method,and were randomly divided into model group,Chonghe paste group and growth factor group,with 12 rats in each group.Another 12 rats were taken to construct normal wound model as normal group.The rats in normal group and model group were treated with normal saline for debridement,while those in Chonghe paste group and growth factor group were treated with Chonghe paste and growth factors for wound coating,respectively.The changes in fasting blood glucose and wound healing were observed and recorded,and samples were collected on the 7th and 14th days after treatment.The expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),P62 and collagen type Ⅲ(COL3)in granulation tissues were detected by immunohistochemistry.The mitochondrial ultrastructure was observed under an electron microscope,and the number of autophagosomes was recorded.The expression of PINK1,parkin and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in wound tissues was detected by immunofluorescence,Western blot and RT-qPCR.RE-SULTS:Compared with normal group,the blood glucose levels of the rats in model group,Chonghe paste group and growth factor group were higher than 16.67 mmol/L on the 7th,14th and 28th days,indicating successful modeling of dia-betes.Compared with normal group,the rats in model group had a lower wound healing rate,the mean absorbance of IL-6,TNF-α and P62 was increased,the mean absorbance of COL3 was decreased,the number of autophagosomes per unit area was increased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was decreased,and the mRNA and protein expres-sion levels of PINK1,parkin and LC3-Ⅱ were decreased.Compared with model group,the wound healing rate of the rats in Chonghe paste group and growth factor group was increased,the mean absorbance of IL-6,TNF-α and P62 was de-creased,the mean absorbance of COL3 was increased,the number of autophagosomes per unit area was decreased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was increased,and the mRNA and protein expression levels of PINK1,parkin and LC3-Ⅱ were elevated.CONCLUSIONS:Chonghe paste can alleviate local inflammatory response in diabetic ulcer wounds,reduce the levels of inflammatory factors IL-6 and TNF-α,promote COL3 expression,activate the PINK1/parkin signaling pathway,and promote mitophagy in wounds,thus accelerating wound healing.
3.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.
4.The Expression of Serum LCN2 and LTBP2 in Ovarian Cancer patients and Their Relationship with Clinicopathological Features and Prognosis
Jiao DANG ; Na WANG ; Linyu HAN
Journal of Kunming Medical University 2025;46(7):118-124
Objective To explore the expression of serum lipocalin-2(LCN2)and latent transforming growth factor-β binding protein 2(LTBP2)in ovarian cancer patients and their relationship with clinicopathological features and prognosis.Methods A total of 108 ovarian cancer patients treated in Baoji Hospital Affiliated to Xi'an Medical College from February 2020 to December 2021 were included in the ovarian cancer group.Another 108 patients with benign ovarian lesions during the same period were included and labeled as the lesion group,and 108 healthy female volunteers undergoing physical examination were assigned to the control group.ELISA method was used to detect serum LCN2 and LTBP2 levels.The relationship between serum LCN2 and LTBP2 levels and prognosis survival rate in ovarian cancer patients was analyzed using the Kaplan-Meier method.Multivariate Cox regression analysis was performed to identify the risk factors affecting the prognosis of ovarian cancer patients.Results Serum LCN2 and LTBP2 levels increased in the control group,lesion group,and ovarian cancer group in sequence(P<0.05).Among patients with high expression of serum LCN2 and LTBP2,the proportions of FIGO stage Ⅲ-Ⅳ,tumor maximum diameter>3 cm,and postoperative lymph node metastasis were higher than those of FIGO stages Ⅰ-Ⅱ,tumor maximum diameter≤3 cm,and non lymph node metastasis(P<0.05).The median survival time of ovarian cancer patients with high serum LCN2 and LTBP2 expression was lower than that of patients with low expression(Log-rank χ2=5.367、6.305,P<0.05).The survival rate of patients with FIGO stage Ⅲ~Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,LCN2 and LTBP2 high expression was lower than that of patients with FIGO stage Ⅰ~Ⅱ,tumor maximum diameter≤3 cm,no postoperative lymph node metastasis,and low LCN2 and LTBP2 expression(P<0.05).FIGO stages Ⅲ-Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,high LCN2,and high LTBP2 were independent risk factors affecting the 3-year survival rate of ovarian cancer patients(P<0.05).Conclusion Serum LCN2 and LTBP2 are upregulated in ovarian cancer patients,and are closely related to FIGO staging,tumor maximum diameter,and postoperative lymph node metastasis.They are important factors affecting prognosis and may serve as biomarkers for evaluating prognosis.
5.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.
6.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.
7.Applicability of a new pilot anti-G capability assessment trainer
Tao JIANG ; Jiao YIN ; Lijun WEN ; Bin LI ; Jiyu DANG ; Xi ZHAO ; Wen DONG ; Haixia WANG ; Yan XU
Chinese Journal of Aerospace Medicine 2025;36(1):38-43
Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.
8.Application status of the model organism zebrafish in radiation medicine research
Juancong DONG ; Jingjie WANG ; Jinhuan YU ; Jiao CHENG ; Xuhong DANG ; Guodong YANG
Acta Laboratorium Animalis Scientia Sinica 2025;33(1):141-148
As a model organism that bridges the gap between cells and traditional mammals,the zebrafish has broad application prospects in radiation medicine research.Among its unique advantages are its characteristics of a high homology with human genes,high fertility,short embryonic period,and transparent and easy to observe embryos,making it an important tool in radiation medicine research.Recently,remarkable progress has been made in the application of zebrafish to investigate low-dose radiation biological effects,radiation therapy,and radiation damage prevention and treatment,key areas of radiation medicine.In this paper,these applications are reviewed;we explore the value of zebrafish in radiation medicine research and provide a reference for experimental research in related fields.
9.Mechanism of Chonghe paste promoting wound healing of diabetic ulcer through PINK1/parkin pathway-mediated mitophagy
Ying DANG ; Yuqi JIAO ; Ri HAI ; Jianping SHI
Chinese Journal of Pathophysiology 2025;41(2):338-347
AIM:To explore the mechanism of Chonghe paste in regulating PTEN-induced kinase 1(PINK1)/parkin pathway-mediated mitophagy on diabetic ulcer wound healing.METHODS:Thirty-six rats were used to construct a diabetic ulcer model by high-sugar and high-fat feed,intraperitoneal injection of streptozotocin and skin defect method,and were randomly divided into model group,Chonghe paste group and growth factor group,with 12 rats in each group.Another 12 rats were taken to construct normal wound model as normal group.The rats in normal group and model group were treated with normal saline for debridement,while those in Chonghe paste group and growth factor group were treated with Chonghe paste and growth factors for wound coating,respectively.The changes in fasting blood glucose and wound healing were observed and recorded,and samples were collected on the 7th and 14th days after treatment.The expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),P62 and collagen type Ⅲ(COL3)in granulation tissues were detected by immunohistochemistry.The mitochondrial ultrastructure was observed under an electron microscope,and the number of autophagosomes was recorded.The expression of PINK1,parkin and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in wound tissues was detected by immunofluorescence,Western blot and RT-qPCR.RE-SULTS:Compared with normal group,the blood glucose levels of the rats in model group,Chonghe paste group and growth factor group were higher than 16.67 mmol/L on the 7th,14th and 28th days,indicating successful modeling of dia-betes.Compared with normal group,the rats in model group had a lower wound healing rate,the mean absorbance of IL-6,TNF-α and P62 was increased,the mean absorbance of COL3 was decreased,the number of autophagosomes per unit area was increased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was decreased,and the mRNA and protein expres-sion levels of PINK1,parkin and LC3-Ⅱ were decreased.Compared with model group,the wound healing rate of the rats in Chonghe paste group and growth factor group was increased,the mean absorbance of IL-6,TNF-α and P62 was de-creased,the mean absorbance of COL3 was increased,the number of autophagosomes per unit area was decreased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was increased,and the mRNA and protein expression levels of PINK1,parkin and LC3-Ⅱ were elevated.CONCLUSIONS:Chonghe paste can alleviate local inflammatory response in diabetic ulcer wounds,reduce the levels of inflammatory factors IL-6 and TNF-α,promote COL3 expression,activate the PINK1/parkin signaling pathway,and promote mitophagy in wounds,thus accelerating wound healing.
10.Applicability of a new pilot anti-G capability assessment trainer
Tao JIANG ; Jiao YIN ; Lijun WEN ; Bin LI ; Jiyu DANG ; Xi ZHAO ; Wen DONG ; Haixia WANG ; Yan XU
Chinese Journal of Aerospace Medicine 2025;36(1):38-43
Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.

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