1.The validation of radiation-responsive lncRNAs in radiation-induced intestinal injury and their dose-effect relationship
Ying GAO ; Xuelei TIAN ; Qingjie LIU ; Hua ZHAO ; Wei ZHANG
Chinese Journal of Radiological Health 2025;34(2):270-278
Objective To explore the feasibility of long non-coding RNAs (lncRNAs) as biomarkers for radiation-induced intestinal injury. Methods Mice were exposed to 15 Gy of 60Co γ-rays to the abdominal area. The pathological changes in intestinal tissues were analyzed at 72 h post-irradiation to confirm the successful establishment of the radiation-induced intestinal injury model. Real-time quantitative PCR was conducted to detect the expression of candidate radiation-responsive lncRNAs in the jejunum, jejunal crypts, colon tissues, and plasma of irradiated mice. Human intestinal epithelial cell line HIEC-6 and human colon epithelial cell line NCM460 were exposed to 0, 5, 10, and 15 Gy of 60Co γ-rays. The expression levels of candidate lncRNAs were measured at 4, 24, 48, and 72 h post-irradiation to observe their changes with the irradiation dose. Results Pathological analysis showed that abdominal irradiation with 15 Gy successfully established an acute radiation-induced intestinal injury mouse model. Real-time quantitative PCR showed that Dino, Lncpint, Meg3, Dnm3os, Trp53cor1, Pvt1, and Neat1 were significantly upregulated following the occurrence of radiation-induced intestinal injury (P < 0.05). Among them, Meg3 and Dnm3os in mouse plasma were significantly upregulated (P < 0.05), while Gas5 was significantly downregulated (P < 0.05). In HIEC-6 and NCM460 cells, the expression levels of DINO, MEG3, DNM3OS, and GAS5 showed dose-dependent patterns at certain time points (P < 0.05). Conclusion The lncRNAs encoded by MEG3, DNM3OS, and GAS5 in intestinal epithelial cells are responsive to ionizing radiation. Consistent differential expression changes were detected in mouse plasma and intestinal tissues, indicating their potential as biomarkers for radiation-induced intestinal injury.
2.Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study
Zhipeng LIU ; Xuelei LI ; Haisu DAI ; Weiyue CHEN ; Yuhan XIA ; Wei WANG ; Xianghao YE ; Zhihua LONG ; Yi ZHU ; Fan HUANG ; Chao YU ; Zhaoping WU ; Jinxue ZHOU ; Dong ZHANG ; Rui DING ; Wei CHEN ; Kecan LIN ; Yao CHENG ; Ping YUE ; Yunfeng LI ; Tian YANG ; Jie BAI ; Yan JIANG ; Wei GUO ; Dalong YIN ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2023;22(7):866-872
Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.
3.Effect of circular RNA hsa_circZDHHC21_004 on the proliferation of the human small intestinal epithelial cells HIEC-6 exposed to 60Co γ-rays
Xuelei TIAN ; Haixiang LIU ; Xue LU ; Mei TIAN ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2023;43(5):321-327
Objective:To study the influence of circular RNA hsa_circZDHHC21_004 on the proliferation of human small intestinal epithelial cells HIEC-6 after 60Co γ-rays exposure. Methods:HIEC-6 cells were exposed to 60Co γ-rays at 0, 5, 10, and 15 Gy with a dose rate of 1 Gy/min. The expression level of hsa_circZDHHC21_004 in the irradiated HIEC-6 cell was detected. Hsa_circZDHHC21_004 was knocked-down to investigate the influences of hsa_circZDHHC21_004 on the proliferation of irradiated HIEC-6 cells by CCK-8 assay and colony formation assay. Results:The expression level of hsa_circZDHHC21_004 in HIEC-6 cells was upregulated by (1.00±0.24), (1.34±0.28), (1.85±0.31), and (2.80±0.64) times of control after 0, 5, 10, and 15 Gy irradiation, respectively and there were significant difference between 10 or 15 Gy group and 0 Gy group ( F=10.86, P=0.008). Knockdown of hsa_circZDHHC21_004 significantly increased the proliferation rate of HIEC-6 cells at 24, 48, and 72 h after 10 Gy irradiation compared with non-irradiated control ( t=-6.25, -5.83, -7.75, P < 0.001). Under 2 and 5 Gy irradiation, the clone formation rates of the hsa_circZDHHC21_004 knockdown cells were significantly higher than those of the control ( t=-7.45, -8.83, P<0.01). Conclusions:Hsa_circZDHHC21_004 is increased after irradiation and influenced the proliferation of irradiated HIEC-6 cells.
4.Analysis of the metabolic characteristics in rat plasma after total body irradiation
Hua ZHAO ; Cong XI ; Xuelei TIAN ; Haixiang LIU ; Mei TIAN ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2021;41(6):401-406
Objective:To investigate the metabolite changes in rat plasma after total body irradiation (TBI) and to explore dose classification based on radiation sensitive metabolites.Methods:The differential metabolites induced by radiation were screened and verified by metabolomics. In the discovery stage, 50 SD rats were irradiated with 0, 1, 2, 3, 5 and 8 Gy of 60Co γ-rays. In the verification stage, 25 rats were irradiated with 0, 0.5, 2.5, 4 and 6 Gy. Peripheral blood samples were collected 4 h after irradiation, and plasma was separated. Radiation-induced differential metabolites were identified and their concentrations were determined. Receiver operating characteristic (ROC) curve of the differential metabolites was used to classify dose range. Results:In the discovery stage, 8 radiation-induced differential metabolites in rat plasma were identified and four of them (cytosine, L-hexylcarnitine, Linoelaidylcarnitine and L-palmitylcarnitine) were upregulated, which was confirmed in the verification stage. The area under the curve (AUC) for the specific dose was >0.75. After combining these four metabolites, the AUC value to classify the radiation dose of 0 Gy versus >0 Gy, <2 Gy versus ≥2 Gy, <5 Gy versus ≥5 Gy were 0.96, 1 and 0.94, respectively.Conclusions:The metabolites in rat plasma changed significantly at 4 h after TBI, where 8 differential metabolites were identified. Cytosine, L-hexylcarnitine, linoelaidylcarnitine and L-palmiylcarnitine were stably over-expressed in the plasma after irradiation. The combination of these four compounds had high classification accuracy and thus may applicable as radiation sensitive biomarkers for dose classification.
5.Cytogenetic analysis of the victim followed-up at 4 year after 192Ir radiation accident in Nanjing
Xue LU ; Hua ZHAO ; Jin WANG ; Shuang LI ; Xuelei TIAN ; Furu WANG ; Mei TIAN ; Ningle YU ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2020;40(3):183-188
Objective:To screen the indicators of retrospective dose estimation, based on 5 cytogenetic methods to assess the victim followed-up at 4 year after 192Ir radiation accident in Nanjing. Methods:The chromosome aberration (dic + r) assay, cytokinesis block micronucleus (MN) and nucleoplasmic bridge (NPB) assay, fluorescence in situ hybridization (FISH)-based and G banding-based translocation analysis were used to retrospective biological dose estimation. Results:The estimated doses of FISH-based and G banding -based analysis were 1.45 and 1.21 Gy respectively, which was similar to the biological dose estimated short time after the accident. However, the estimated doses by chromosome aberration, micronucleus and nucleoplasmic bridge method were 0.56, 0.45 and 0.41 Gy respectively, which were lower than the corresponding biodose. Correction factors were used to adjust the biodose.Conclusions:In the 4th years after exposure, the estimated biological doses by FISH-based and G banding-based translocation were consistent with the biodose.Therefore, the two methods were suitable for retrospective dose estimation, while correction factors should be considered in chromosome aberration method for retrospective dose estimation.
6.Premature senescence and the protein expressions of P53 and P16 in HaCaT cells after UVB exposure
Juan YAN ; Qingjie LIU ; Mei TIAN ; Xue LU ; Tianjing CAI ; Shuang LI ; Hua ZHAO ; Xuelei TIAN ; Deqing CHEN ; Ling GAO
Chinese Journal of Radiological Medicine and Protection 2020;40(4):284-289
Objective:To explore the effects of ultraviolet B (UVB) on the premature senescence of human immortalized keratinocytes HaCaT cells and the possible underlying molecular mechanism.Methods:HaCaT cells were exposed with UVB of different doses (20, 50, 80 and 100 mJ/cm 2). At 72 h after exposure, cellular morphology was observed by Giemsa staining, cell proliferation was detected by clone formation assay, and the proportion of premature senescence cells was detected by β-galactosidase staining. The number change of lysosomes was detected by Lyso-Tracker Red fluorescence probe at 24, 48 and 72 h after exposure. Cell migration was measured by scratch test at 24 h and 48 h after exposure. The protein expressions of p53 and p16 related to premature senescence were detected by Western blot assay at 72 h after exposure. Results:After UVB exposure, HaCaT cells showed a premature senescence phenotype. At 72 h after exposure, the cell volume increased ( F=115.18, P<0.05), the cell proliferation ability decreased ( F=410.32, P<0.05), the activity of β-galactosidase increased ( F=16.31, P<0.05), and the expressions of P53 and P16 increased. In addition, the number of lysosomes increased at 24, 48, and 72 h after exposure ( F=17.65, 38.36, 13.66, P<0.05), and cell migration capacity was inhibited at 24 and 48 h after exposure ( F=8.21, 11.48, P<0.05). Conclusions:UVB exposure can induce premature senescence of HaCaT cells by increasing the expression of p53 and p16 proteins.
7.Screening of radiosensitive lipid metabolites in rat plasma
Hua ZHAO ; Xuelei TIAN ; Cong XI ; Ling GAO ; Mei TIAN ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2020;40(6):420-426
Objective:To screen radiosensitive lipid metabolites in rat plasma and analyze their metabolic pathways in order to provide scientific basis for radiation damage biomarker.Methods:The whole body irradiation of 60Co γ rays was performed to rats with different doses of 0, 1, 3 and 5 Gy. The changes of lipids in plasma were detected by untargeted lipidomics method based on liquid chromatography coupled mass spectrometry. Results:Twenty plasma lipids were identified as the potential radiosensitive biomarkers at 7 days after irradiation, including 13 over-expressed lipids and 7 down-expressed lipids, where 12 lipids well responded to radiation doses.Conclusions:Lipid metabolites in rat plasma are significantly changed after exposure to γ rays, and the metabolic pathways of sphingolipid, glycerophospholipid and glycosylphosphatidylinositol (GPI) are significantly enriched.
8. Influence factors of nucleoplasmic bridge frequencies in the peripheral blood lymphocytes of radiation workers
Xuelei TIAN ; Xue LU ; Jiangbin FENG ; Yumin LYU ; Mei TIAN ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2020;40(2):94-98
Objective:
To study the effects of sex, age, length of service, type of work and annual effective radiation dose on nucleoplasmic bridge (NPB) in the peripheral blood lymphocytes of radiation workers.
Methods:
The peripheral blood samples of 100 radiation workers in Henan province were collected and the NPB in peripheral blood lymphocytes were measured by CBMN assay. The frequencies of NPB formation and NPB-containing cells were calculated, and the effects of various factors on NPB incidence were analyzed statistically.
Results:
The NPB frequency in radiation workers was higher than that in healthy people (
9. Establishment and validation of the dose-response curve of X-rays irradiation and chromosome aberrations in human peripheral blood cells
Xue LU ; Shuang LI ; Tianjing CAI ; Xuelei TIAN ; Mei TIAN ; Qingjie LIU
China Occupational Medicine 2019;46(06):705-708
OBJECTIVE: To explore the dose-effect of X-ray irradiation and chromosome aberrations in human peripheral blood cells,and establish a dose-response curve of dicentric and ring(dic+r)aberration induced by X-ray irradiation.METHODS: Human peripheral blood samples were collected from three healthy individuals and were exposed to X-ray at the doses of 0.00,0.25,0.50,0.75,1.00,2.00,3.00,4.00 and 5.00 Gy in vitro.The dose rate was 1.158 Gy/min.The blood cells were harvested after routine culture,and the chromosome preparation was carried out.The dicentrics and rings in metaphase cells were counted under microscope,and a dose-response curve was fitted by using the software of CABAS.Dose estimation was performed according to the curve from two blind samples.RESULTS: Aberration of dic+r increased with irradiation doses in the range of 0.00-5.00 Gy(P<0.01).The dose-response relationship followed a linear-quadratic equation:■,where■ is the yield of dic+r,and D is the irradiated dose.The estimated doses of the two blind samples were in accordance with the actual doses.CONCLUSION: The dose-response curve and mathematical model of chromosome aberration following exposure to 0.00-5.00 Gy X-ray irradiation is established in this study provide a reliable method for the accurate dose estimation.
10.Serial Frozen Fecal Microbiota Transplantation in the Treatment of Chronic Intestinal Pseudo-obstruction: A Preliminary Study.
Lili GU ; Chao DING ; Hongliang TIAN ; Bo YANG ; Xuelei ZHANG ; Yue HUA ; Yifan ZHU ; Jianfeng GONG ; Weiming ZHU ; Jieshou LI ; Ning LI
Journal of Neurogastroenterology and Motility 2017;23(2):289-297
BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) is a serious, life-threatening motility disorder that is often related to bacterial overgrowth. Fecal microbiota transplantation (FMT) results in restoration of the normal intestinal microbial community structure. We investigated the efficacy of FMT in the treatment of CIPO patients. METHODS: Nine patients (age 18–53 years) with CIPO were enrolled in this prospective, open-label study. Patients received FMT for 6 consecutive days through nasojejunal (NJ) tubes and were followed up for 8 weeks after treatment. We evaluated the rate of clinical improvement and remission, feeding tolerance of enteral nutrition, and CT imaging scores of intestinal obstructions. Lactulose hydrogen breath tests were performed before FMT and 8 weeks after FMT to evaluate for the presence small intestinal bacterial overgrowth (SIBO). RESULTS: FMT significantly alleviated bloating symptoms, and symptoms of pain were relieved 2 weeks after FMT. Enteral nutrition administered through a NJ tube after FMT was well-tolerated by 66.7% (6/9) of patients. CT scores of intestinal obstructions were significantly reduced after FMT (P = 0.014). SIBO was eliminated in 71.0% (5/7) of patients. CONCLUSIONS: This pilot study demonstrated the safety of using FMT. FMT may relieve symptoms in selected patients with CIPO. FMT may also improve patient tolerance of enteral nutrition delivered via a NJ tube.
Breath Tests
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Enteral Nutrition
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Fecal Microbiota Transplantation*
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Humans
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Hydrogen
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Intestinal Obstruction
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Intestinal Pseudo-Obstruction*
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Lactulose
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Pilot Projects
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Prospective Studies

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