1.Proteomic analysis of differentially expressed proteins in mice plasma following FLASH and conventional dose rate whole-lung irradiation
Hui LUO ; Liuxiang WANG ; Ron LEAVITT ; Jackie ROMERO ; Marie-Catherine VOZENIN ; Aymeric ALMEIDA ; Chengliang YANG ; Na LI ; Xuenan WANG ; Ronghu MAO ; Leijie MA ; Hongchang LEI ; Hong GE
Chinese Journal of Radiological Medicine and Protection 2025;45(10):941-948
Objective:To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method.Methods:A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation ( n = 5) and whole-lung FLASH irradiation ( n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results:Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes.Conclusions:Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect.
2.Proteomic analysis of differentially expressed proteins in mice plasma following FLASH and conventional dose rate whole-lung irradiation
Hui LUO ; Liuxiang WANG ; Ron LEAVITT ; Jackie ROMERO ; Marie-Catherine VOZENIN ; Aymeric ALMEIDA ; Chengliang YANG ; Na LI ; Xuenan WANG ; Ronghu MAO ; Leijie MA ; Hongchang LEI ; Hong GE
Chinese Journal of Radiological Medicine and Protection 2025;45(10):941-948
Objective:To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method.Methods:A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation ( n = 5) and whole-lung FLASH irradiation ( n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results:Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes.Conclusions:Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect.
3.Screening of Hub genes contributing to acute T lymphoblastic leukemia induced by ultra-high dose rate radiotherapy based on GEO database
Hui LUO ; Liuxiang WANG ; Leavitt RON ; Yanan SUN ; Shuai SONG ; Xiaohui WANG ; Ronghu MAO ; Leijie MA ; Hongchang LEI ; Hong GE
Chinese Journal of Radiological Medicine and Protection 2022;42(10):738-744
Objective:To analyze the data of ultra-high dose rate (FLASH) radiotherapy in GEO (Gene Expression Omnibus) database by bioinformatics method, in order to find the hub genes involved in flash radiotherapy induced acute T-lymphoblastic leukemia.Methods:The gene expression profiles of malignant tumors receiving FLASH radiotherapy were downloaded from GEO database. The R software was used to screen the differential expressed genes (DEGs) and analyze their biological functions and signal pathways. The protein-protein interaction (PPI) network of DEGs was analyzed by online tool of STRING, and Hub genes were screened by Cytoscape plug-in. The expressions of screened Hub genes in acute T lymphoblastic leukemia were identified with TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database.Results:Based on the analysis of GSE100718 microarray dataset of GEO database, a total of 12 800 genes were found to be associated with radiosensitivity of acute T lymphoblastic leukemia, of which 61 significantly altered DEGs were selected for further analysis. It was found that these genes were involved in the biological processes of metabolism, stress response, and immune response through the pathways of oxidative phosphorylation, unfolded protein response, fatty acid metabolism, and so on. PPI analysis indicated that HSPA5 and SCD belonged to the Hub genes involved in the regulation of FLASH radiosensitivity, and they were significantly highly expressed in acute T lymphoblastic leukemia combined with TRD/LMO2-fusion gene.Conclusions:Through bioinformatics analysis, the Hub genes involved in regulating the sensitivity of FLASH radiotherapy and conventional radiotherapy can be effectively screened, and thus the gene expression profiles can be used to guide the stratification of cancer patients to achieve a precise radiotherapy.
4.Validity and Reliability of Chinese Physical Activity Questionnaire for Children Aged 10-17 Years.
Xi YANG ; Russell JAGO ; Yi ZHAI ; Zhen Yu YANG ; Yu Ying WANG ; Xiang SI ; Jun WANG ; Jian Fen GAO ; Jing Ron CHEN ; Ying Jie YU ; Wen Hua ZHAO
Biomedical and Environmental Sciences 2019;32(9):647-658
OBJECTIVE:
This study is aimed to report the development, the reliability and validity of the Chinese Children Physical Activity Questionnaire (CCPAQ) which was designed for the assessment of physical activity pattern in young population in China.
METHODS:
The CCPAQ was administered for two times in 119 children (mean age 13.1 ± 2.4 years; boys 47%) to examine reliability by using intraclass correlation coefficients. Validity was determined in 106 participants by agreement with the CCPAQ measures and the objective method, the ActiGraph accelerometer. Data on physical activity pattern including time spent on different intensities and total physical activity, sedentary behavior as well as physical activity energy expenditure were used to assess the validity with Spearman's correlation coefficient and the Bland-Altman plots.
RESULTS:
The reliability coefficient of the CCPAQ ranged from 0.63-0.93 (Intra-class correlation coefficient). Spearman's correlation coefficient for validity of time spent on total physical activity and sedentary behavior were all 0.32 (P < 0.001), and for physical activity energy expenditure was 0.58 (P < 0.001). Time spent on moderate-to-vigorous physical activity and light physical activity showed a relatively low correlation with the accelerometer (rho = 0.20, P = 0.040; rho = 0.19, P = 0.054).
CONCLUSION
The CCPAQ appears to be a promising and feasible method to assess physical activity pattern in Chinese children.
5. Effectiveness of integrated early childhood development intervention on nurturing care for children aged 0-35 months in rural China
Huifeng SHI ; Jingxu ZHANG ; Xiaoli WANG ; Yuanyuan XU ; Shengli DONG ; Chunxia ZHAO ; Xiaona HUANG ; Qi ZHAO ; Xuefeng CHEN ; Ye ZHOU ; Margo O'SULLIVAN ; Ron POUWELS ; Robert W. SCHERPBIER
Chinese Journal of Pediatrics 2018;56(2):110-115
Objective:
To explore whether Integrated Early Childhood Development (IECD) program has effectively improved the nurturing care for children aged 0-35 months in rural China.
Methods:
IECD has been implemented by the government of China with support from the United Nations Children's Fund (UNICEF) in four poverty-stricken rural counties since 2014. The interventions targeting the five key components of nurturing care (i.e. child and caregiver health, child nutrition, early learning support, child protection and social security) were delivered through the IECD program to children aged 0 to 35 months and their caregivers. A population-based intervention trial was designed to evaluate intervention effectiveness with data collected in 2013 (baseline) and 2016 (mid-term). The changes of nurturing care in the intervention and control group were analyzed by using a difference-in-differences (DID) model. This approach provided adjustment for sociodemographic and other confounding factors.
Results:
The baseline and mid-term survey enrolled 1 468 and 1 384 children in the intervention group, and 1 485 and 1 361 in the control group. After two years of implementation, the prevalence of caregiver's depression in the intervention group showed a decrease of 9.1% (mid-term 34.8% (479/1 377)
6.Observation on therapeutic effect of pecking moxibustion of specific acupoints for treatment of irritable bowel syndrome (diarrhea type).
Hao-ron CHU ; Zai-hong WANG ; Jun YANG ; Hong-bing KONG ; Fei LI
Chinese Acupuncture & Moxibustion 2009;29(2):111-113
OBJECTIVETo compare therapeutic effects of pecking moxibustion therapy and common acupuncture on irritable bowel syndrome (diarrhea type).
METHODSFifty cases of irritable bowel syndrome were randomly divided into a pecking moxibustion group (n=30) and an acupuncture group (n=20). The pecking moxibustion group was treated by pecking moxibustion with a ZHOU's pecking moxibustion pen, and the acupuncture group by common acupuncture. In the two groups, Ganshu (BL 18), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), etc. were selected. After treatment of 15 sessions the scores of symptoms and clinical therapeutic effects were compared between the two groups.
RESULTSAfter treatment, the scores of symptoms significantly decreased (both P < 0.01), with a significant difference in the decrease of symptom scores between the two groups (P < 0.05); the total effective rate of 93.3% in the pecking moxibustion group was higher than 75.0% in the acupuncture group (P < 0.05).
CONCLUSIONPecking moxibustion therapy can significantly improve the clinical symptoms of irritable bowel syndrome (diarrhea type), with a better therapeutic effect than common acupuncture.
Acupuncture Points ; Adolescent ; Adult ; Aged ; Diarrhea ; therapy ; Female ; Humans ; Irritable Bowel Syndrome ; therapy ; Male ; Middle Aged ; Moxibustion ; Young Adult
7.A sharp rise in portal vein pressure, not arterial constriction, initiates bile salt-induced pancreatic microcirculatory disturbance.
Youdai CHEN ; Huaiqing CHEN ; Yunman TANG ; Qiufen TU ; Dongxia GE ; Chang YU ; Congxun JIANG ; Shiping LIAO ; Ron WANG
Journal of Biomedical Engineering 2007;24(6):1280-1285
It was reported that pancreatic arteries constricted during the early phase of bile salt-induced acute pancreatitis (AP), leading to pancreatic microcirculatory disturbance. We conducted this experiment to verify whether the above-mentioned finding was true. AP was induced with intraductal injection of taurodeoxyholate. Small pancreatic artery pressure in dogs was recorded. Functional capillaries were counted and calibrated by multiplying wet weight of pancreas. Pancreatic perfusion was measured with Laser Doppler flowmeter. Pancreatic arterioles of rats dilated during the initial 20 min of AP, and pancreatic arterial pressure declined during the early phase of AP in dogs (from 104.5 +/- 4.8 mmHg to 54.6 +/- 5.6 mmHg). The hematocrit of blood from inferior vena cava was significantly lower than that of portal vein at 5 min after pancreatitis induction. The "true" pancreatic functional capillary density increased. The early pancreatic microcirculatory disturbance coincided with a marked increase of portal vein pressure (PVP) as high as 9.18 +/- 0.78 mmHg. Reduction of PVP to baseline level was followed by a marked increase of pancreatic perfusion (by 1.4-fold). Arterial dilatation, but not constriction, occurred during the early phase of bile salt-induced AP. The pancreatic microcirculatory disturbance was due to a marked rise in PVP that greatly reduced the pressure difference in the pancreatic blood vessels and increased plasma extravasation which led. to local hemoconcentration.
Animals
;
Bile Acids and Salts
;
adverse effects
;
Hypertension, Portal
;
complications
;
Male
;
Microcirculation
;
drug effects
;
physiology
;
Pancreas
;
blood supply
;
Pancreatitis
;
etiology
;
physiopathology
;
Portal Pressure
;
Portal Vein
;
physiopathology
;
Rats
;
Rats, Sprague-Dawley

Result Analysis
Print
Save
E-mail