1.Dynamic changes of VEGF mRNA and protein due to brain injury in irradiated rats
Chenying MA ; Xiaoting XU ; Yu TU ; Juying ZHOU
Chinese Journal of Radiological Medicine and Protection 2014;34(6):405-410
Objective To investigate the dynamic changes of VEGF mRNA and protein in the injured brain of rats irradiated by 20 Gy of electron beams.Methods A total of 114 Sprague-Dawley rats were randomly divided into two groups,42 rats in sham group with sham-irradiation,and the other 72 rats in irradiation group that the whole brains of rats were administered with a single dose of 20 Gy electron beam (6 MeV) to establish an animal model of radiation-induced brain injury.All rats were terminated at 1,3,7,14,28,42,56 d post-irradiation respectively.The pathological changes were observed with light microscopies.Real-time quantitative reverse transcriptase-PCR was used to measure the level of VEGF mRNA in the brain tissue.The expression of VEGF protein in whole brain tissue was detected with Western blot.The VEGF protein expression in brain endothelium,gliacyte and neuron were measured via immunohistoehemistry with computerized image processing.Results The pathological process of radiationinduced brain injury (RBI) included brain endothelial cell damage,brain edema,thrombosis formation and ablation,revascularization and angiogenesis.In the irradiation group,the expression of VEGF mRNA was declined significantly at 1,3,7,2g,42 d post-irradiation (t =16.275-46.118,P < 0.05).The VEGF protein expression in whole brain tissue was up-regulated at 1 and 7 d after irradiation,but downregulated at 3,14,28,42,56 d post-irradiation.There were VEGF positive cells in the brain endothelium,gliacyte and neuron at 1 d after irradiation.The expression of VEGF protein in gliacyte and neuron significantly was increased at 1,14,42,56 d post-irradiation (t =-8.394--4.697,P < 0.05),and increased significantly in brain endothelial cells at 1,14,and 42 d after irradiation (t =-5.554--4.159,P < 0.05).Conclusions The expression of VEGF mRNA was relatively suppressed in RBI rats.The expression of VEGF protein in whole brain tissue was up-regulated only at the early stage of RBI.The expressions of VEGF protein in brain endothelium,gliacyte and neuron were increased in the observation period,which induced brain edema and the formation of thrombosis at the acute RBI stage,and participated in the progression of angiogenesis and thrombosis ablation at the early-delayed RBI stage.
2.Stratified study of high-risk colorectal neoplasm population in patients undergoing coronary artery angiography examination
Xiaobo YANG ; Luying SUN ; Chenying XU ; Weiwei LI ; Xianxing CHANG ; Lifen YU
Chinese Journal of Digestion 2013;(3):171-175
Objective To investigate the difference between Asia-Pacific Colorectal Screening (APCS) scoring system and colorectal cancer sequential screening criteria issued by the Health Ministry of China (China sequential criteria) in the evaluation of high-risk colorectal neoplasm in patients undergoing coronary artery angiography (CAG) examination.Methods The data of 870 patients aged from 40 to 74 who underwent CAG examination were retrospectively analyzed.The measurement data were analyzed by t test and the count data were aralyzed by x2 test.Results There were 72 patients aged from 40 to 49 years old.Among them,eight patients were stratified as high-risk population according to the Chinese sequential criteria; however there was no high-risk population by APCS.There were 798 patients aged from 50 to 74 years old.There were 460 patients stratified as high-risk population by APCS.The percentage of CAG negative group (34.7%) was significantly lower than that of the coronary artery disease (CAD) group (68.0%,x2 =77.74,P<0.01).According to the Chinese sequential criteria,and there were 134 patients stratified as high-risk population,and there was no significant difference between the CAG negative group (17.7 %) and the CAD group (16.4%,P>0.05).Among the patients aged from 50 to 74 years old without family history of colorectal cancer in first-degree relatives,72 cases (29.0%) of the CAG negative group and 316 cases (57.5%) of the CAD group were stratified as high-risk according to APCS,however not stratified as high-risk by the Chinese sequential criteria.About 90.5 % (351/388) of them were male smokers.According to APCS,30 cases (12.1%) of the CAG negative group and 32 cases (5.8%) of the CAD group were stratified as middle-risk population,however stratified as high-risk population by the Chinese sequential criteria.About 75.8% (47/62) of them were female non-smokers.Conclusions The percentage of patients stratified as high-risk population by APCS was higher than that by the Chinese sequential criteria.In patients aged from over 50 to 74 years old and without family history of colorectal cancer in first-degree relative,APCS maybe overestimated the risk degree of colorectal neoplasm in male smokers and underestimated the risk degree in female non-smokers.
3.The impact of double-balloon enteroscopy on the evolution of detection and surgical treatment for small bowel stromal tumors
Lifen YU ; Chenying XU ; Jie ZHONG ; Shidan CHENG ; Weiguo HU ; Yonghua TANG
Chinese Journal of Digestive Endoscopy 2013;30(5):257-260
Objective To investigate the role of double-balloon enteroscopy (DBE) in the evolution of detection and surgical treatment of small bowel stromal tumors (SBSTs),based on nine years experience.Methods In this retrospective study,193 patients with localized SBSTs were divided into the CT-enterography (CTE) and/or DBE group (n =100) and conventional modalities group (n =93).These patients were further divided into the open surgery group (n =126) and laparoscopy-assisted resection group (n =67).The development of clinical diagnosis and surgical treatment strategies were compared before and after the introduction of DBE.Results The average age and tumor size were significantly smaller in the CTE and/or DBE group than those in the conventional modalities group,respectively (age:50.9 ± 12.1 vs.56.9 ± 11.6 years; tumor size:3.6 ± 1.3 vs.6.1 ± 2.6 cm,P < 0.01).Before the introduction of DBE (from January 2001 to December 2002),all patients underwent conventional modalities,and only 4 cases/year for open surgery.Afterward,from January 2003 to December 2004,84.6% (11/13) of SBSTs were detected by DBE.From January 2005 to December 2008,50.0% (23/46) of SBSTs were found by CTE combination with DBE.From January 2009 to December 2011,80.5% (33/41) of SBSTs were diagnosed by CTE,and the number of patients underwent operation increased up to 25 cases/year,which was nearly 5.3 folds higher than that before the introduction of DBE.Sixty-seven patients were successfully operated by laparoscopy-assisted resection,82.1% (55/67) of them were detected by CTE ands/or DBE,89.1% (49/55) of whom had low-or intermediate-risk SBSTs.Conclusion DBE plays an important role in optimizing the algorithm of detection and treatment of SBSTs.
4.The role of previous gastroscopy in evaluation of concomitant use of PPIs in patients with non-acute coronary syndrome after percutaneous coronary intervention
Xiaobo YANG ; Lifen YU ; Chenying XU ; Weiwei LI ; Luying SUN ; Xianxing CHANG
Chinese Journal of Digestive Endoscopy 2013;(3):133-137
Objective To evaluate previous gastroscopy before percutaneous coronary intervention (PCI) for the risks and benefits of concomitant use of proton pump inhibitors (PPIs) after PCI in patients with non-acute coronary syndrome (non-ACS).Methods The data of 673 non-ACS patients who underwent PCI with stenting were retrospectively analyzed.They were divided into concomitant use of PPIs group and non-PPIs group,then subdivided into high-,moderate-and low-risk groups according to risk factors associated with adverse upper gastrointestinal (GI) events.The incidences of adverse cardiovascular events and adverse upper GI events were compared among groups.Findings of previous gastroscopy were also included.Results Only 82 patients (12.2%) underwent gastroscopy within 5 years before PCI,of whom,27 (32.9%) were diagnosed as having peptic ulcer,and 55.6% (15/27) of whom were in concomitant use of PPIs.Compared with the non-PPIs group,the rate of adverse cardiovascular events in the concomitant use of PPIs group was significantly higher (22.6% vs.8.9%,P <0.01),and the highest rate (41.7%) was in the high-risk group.However,the corresponding rate of adverse upper GI events was the lowest (4.2%).In the moderate-risk group,90.5 % (344/380) of patients were older than 65 years with concomitant use of NSAIDs.The rate of gastroscopy within 5 years before PCI in these patients was remarkably lower than that in patients who had the history of upper GI disease with concomitant use of NSAIDs (concomitant use of PPIs group 14.1% vs.54.5% ; non-PPIs group 7.5% vs.28.0% ; P < 0.01).In the concomitant use of PPIs group,the rate of adverse cardiovascular events in the former was notably higher than that in the latter (20.5% vs.9.1%,P <0.01),but the rate of adverse upper GI events within 1 year after PCI were similar (9.0% vs.9.1%).Conclusion Previous gastroscopy before PCI could provide the baseline information of upper GI disease,which may be helpful for the evaluation of concomitant use of PPIs after PCI so as to decrease the incidence of adverse cardiovascular events.Special attention should be paid to those patients older than 65 years in the moderate-risk group and concomitant use of NSAIDs.
5.Research progress of gut microbiota in the treatment of malignant tumors
Xiaolan HE ; Chenying MA ; Xiaoting XU
Chinese Journal of Radiological Medicine and Protection 2019;39(6):476-480
In recent years,the relationship between gut microbiota and malignant tumors has been a hot topic.Beneficial gut microbiota microenviroment can promote the efficacy of anti-PD-1-based immunotherapy against epithelial or melanoma,and this efficacy can be achieved by fecal microbiota transplantation.For patients who have received pelvic radiotherapy,gut microbiota composition is significantly changed,and taking probiotics can reduce the radiation-induced toxicities such as diarrhea caused by radiotherapy.The studies have shown that the gut microbiotaof patients who have been given chemotherapy had changed significantly.So improving the related bacteria number can increase the efficacy and tolerance.Balancing the gut microbiome is expected to be a new supportive therapy for the treatment of malignant tumors.
6. Correlation between the expression of metabolites and acute radiation enteritis in patients with cervical cancer
Xiaolan HE ; Chenying MA ; Xiaoting XU
Chinese Journal of Radiological Medicine and Protection 2020;40(1):1-10
Objective:
To investigate the relationship between the metabolites in the fecal samples from cervical cancer patients and radiation-induced acute intestinal symptoms during radiotherapy.
Methods:
A total of 51 cervical cancer patients who received radiotherapy in our hospital from September 2017 to June 2018 were enrolled. One patient was excluded due to efficiant sample failure, so a total of 50 patients were included in the study. Totally 200 fecal samples were collected at four time points, i. e. before radiotherapy, 2 weeks post radiotherapy starting, 4 weeks post radiotherapy starting and end of radiotherapy. These fecal samples were analyzed by non-targeted metabolomics using liquid chromatography-mass spectrometry (LC-MS). Data were analyzed with statistical method including partial least squares-discriminant analysis (PLS-DA), agglomerate hierarchical clustering to investigate the trend of metabolites expression in feces.
Results:
A total of 5 770 metabolic peaks were detected and 121 biomarkers were identified, of which 77 biomarkers were up-regulated and 44 biomarkers were down-regulated. Nineteen biomarkers were significantly changed at four time points after radiotherapy, including 1-methylxanthine, linoleic acid, 5-aminopentanoic acid, phenethylamine, styrene, N-acetylglutamate, nandrolone, 4-acetylaminobutyric acid, N-acetyl-L-phenylalanine, daidzein, cholic acid, arachidonic acid, methyl leucine, N-formyl-L-methionine, quercetin, phenylalanine, gluconic acid, melibiose and α-CMBHC. Four metabolic pathways of phenylalanine tyrosine, niacin and nicotinamide, linoleic acid and lysine degradation (Pathway imPact >0.1) were found to be related to acute radiation enteritis.
Conclusions
The metabolites in the feces of cervical cancer patients change significantly during radiotherapy, and some biomarkers in the fecal supernatant are up- or down-regulated to varying degrees as doses increase, which provides new ideas and method for the prediction of acute radiation enteritis.
7.Prognostic value of TCBI in middle-aged and elderly patients with thoracic esophageal squamous cell carcinoma receiving radiotherapy
Tingting JIANG ; Xiaoting XU ; Songbing QIN ; Chenying MA ; Juying ZHOU
Journal of International Oncology 2020;47(4):205-210
Objective:To investigate the prognostic value of TCBI in middle-aged and elderly patients with thoracic esophageal squamous cell carcinoma (ESCC) who received radiotherapy.Methods:The clinical data of 191 patients with thoracic ESCC who underwent radiotherapy in the department of Radiation Oncology of the First Affiliated Hospital of Soochow University from January 2010 to December 2015 were retrospectively analyzed. According to the TCBI value on admission [TCBI=serum triglyceride (mg/dl) × total cholesterol (mg/dl) × body weight (kg)/1 000], patients were divided into TCBI low-value group ( n=79) and TCBI high-value group ( n=112). The relationships between TCBI and clinicopathological characteristics of patients were analyzed. The Kaplan-Meier method was used to calculate the overall survival (OS). The log-rank test was adopted to compare the differences in survival between different groups. The Cox proportional hazard model was used to analyze the factors affecting the prognosis of middle-aged and elderly patients with thoracic ESCC. The receiver operating characteristics (ROC) curve was applied to verify the accuracy of TCBI for survival prediction. Results:The mean pre-radiotherapy TCBI was 1 082±945 in all patients. The cutoff value of the TCBI was 749. The patients with TCBI<749 served as the TCBI low-value group , and patients with TCBI≥749 served as the TCBI high-value group. TCBI was associated with treatment ( χ2=4.235, P=0.040) and geriatric nutritional risk index (GNRI, χ2=8.795, P=0.003). Univariate analysis suggested that male ( HR=2.220, 95% CI: 1.223-4.030, P=0.009), stage N 1-3 ( HR=1.453, 95% CI: 1.023-2.065, P=0.037), GNRI<98 ( HR=1.949, 95% CI: 1.168-3.255, P=0.011) and TCBI<749 ( HR=1.846, 95% CI: 1.298-2.627, P=0.001) were risk factors affecting OS in middle-aged and elderly patients with thoracic ESCC. Besides, postoperative adjuvant radiotherapy ( HR=0.641, 95% CI: 0.449-0.915, P=0.014) was a protective factor. Furthermore, multivariate analysis showed that male ( HR=2.147, 95% CI: 1.173-3.929, P=0.013) and TCBI<749 ( HR=1.664, 95% CI: 1.166-2.376, P=0.005) were independent risk factors for OS. Besides, postoperative adjuvant radiotherapy ( HR=0.630, 95% CI: 0.439-0.903, P=0.012) was an independent protective factor. The area under the curve calculated by the ROC curve was 0.619, the sensitivity was 0.742, and the specificity was 0.496 ( P=0.007), confirming the role of TCBI in the prognostic evaluation. Survival analysis showed that the median OS of patients in the TCBI high-value group was 42 months, and the 1-year and 3-year survival rates were 86.6% and 52.7%, significantly higher than those in the TCBI low-value group (20 months, 68.4% and 29.1% respectively; χ2=12.286, P<0.001). Subgroup analysis showed that among patients with radical radiotherapy, 3-year survival rate in patients with lower TCBI ( n=37) was lower than that in patients with higher values ( n=36) (21.6% vs. 44.4%, χ2=8.505, P=0.004). Conclusion:TCBI is a predictor of OS for middle-aged and elderly patients with thoracic ESCC who received radiotherapy. The lower the TCBI, the poorer the survival prognosis.
8.Analysis of the effectiveness and safety of early radiotherapy intervention in oligometastatic non-small cell lung cancer
Chenying MA ; Xiaoting XU ; Songbing QIN ; Yandong LIU ; Jiao XUE ; Juying ZHOU
Chinese Journal of Radiological Medicine and Protection 2021;41(10):726-734
Objective:To investigate the prognostic factors of oligometastatic (OM) non-small cell lung cancer (NSCLC) patients and the safety and effectiveness of early radiotherapy intervention.Methods:A retrospective analysis was conducted, including 159 OM NSCLC cases (metastatic sites≤5, metastasis organs≤3) admitted to Department of Radiation Oncology in First Affiliated Hospital of Soochow University from January 2015 to December 2018. Among 159 cases, there were 107 males and 52 females, with the median age of 63 years. 137 cases were administrated via early radiotherapy intervention, and 22 cases via delayed radiotherapy intervention. The receiver operating characteristic curve (ROC) was used to determine the progression-free survival time (PFS)/overall survival time (OS) to ascertain the best cut-off value for local control and prognosis. Survival analysis was calculated by Kaplan-Meier curves, and Log rank test was used for comparison of these curves. Cox proportional hazards regression model was used for multivariate survival analysis.Results:The median follow-up time of 159 cases was 28.2 months. During the follow-up period, there were 16 cases with complete remission (10.1%), 53 cases with partial remission (33.3%), 27 cases with stable disease (17.0%), and 63 cases with progressed disease(39.6%). The local control rates at 3, 6 and 12 months were 83.9%, 59.7% and 41.0%, respectively. The median progression-free survival (PFS) of 159 patients was 8.0 months, the median survival time (OS) was 35.0 months, and 1, 2, and 3-year survival rates were 77.3%, 63.0% and 45.1%, respectively. Adverse reactions related to radiotherapy were relatively mild, mostly grade 1 and 2. PFS/OS= 0.3 is the best cut-off value for determining the patient′s local control and prognosis. The result of univariate analysis showed that gender, number of OM organs, T staging, radiotherapy intervention mode, tumor target volume absorbed dose (DT-GTVnx), PFS/OS were significantly related to median PFS ( χ2=4.175, 16.508, 4.408, 10.300, 6.842, 38.175, P<0.05); gender, pathological type, number of OM organs, initial diagnosis stage, T stage, N stage, lobectomy, radiotherapy intervention mode, tumor target volume (V-GTVnx), tumor load, local control status were significantly related to median OS ( χ2=6.672, 8.330, 21.299, 5.398, 6.874, 6.893, 5.611, 115.206, 4.017, 5.110, 21.299, P< 0.05). The result of multivariate analysis showed that delayed radiotherapy intervention ( HR=3.728, 95% CI 2.099-6.622, P<0.001) was an independent risk factor for PFS in patients with OM NSCLC, and PFS/OS>0.3 ( HR=0.123, 95% CI 0.062-0.246, P<0.001) was an independent protective factor for PFS in patients with OM NSCLC; male ( HR=1.665, 95% CI 1.024-3.043, P=0.033), high tumor burden ( HR=2.113, 95% CI 1.088-4.107, P=0.027), delayed radiotherapy interventions ( HR=15.076, 95% CI 7.925-28.680, P<0.001) were independent risk factors for OS in patients with OM NSCLC. Conclusions:OS of patients with OM NSCLC is significantly prolonged in female, low tumor burden and early radiotherapy intervention. Early radiotherapy intervention significantly improved the prognosis, and radiotherapy-related adverse reactions could be tolerated. These might suggest that local radiotherapy is safe and effective in the treatment of OM NSCLC patients.
9.Progression of radiotherapy for brain metastases in non-small cell lung cancer
Huan JI ; Juying ZHOU ; Chenying MA ; Xiaoting XU ; Songbing QIN
Journal of International Oncology 2022;49(3):181-184
Brain metastases are one of the most common distant metastases in patients with non-small cell lung cancer (NSCLC), and the prognosis will be extremely poor. The effect of chemotherapy and operation is limited. As a standard treatment, radiotherapy is widely used in clinical practice. Radiotherapy alone includes whole brain radiotherapy, stereotactic radiotherapy and whole brain radiotherapy combined with stereotactic radiotherapy. With the continuous development of radiotherapy and the progress of gene sequencing, radiotherapy has been combined with targeted drugs, anti-angiogenic drugs and immunodrugs in the treatment of NSCLC brain metastasis, which can improve the survival of patients with NSCLC brain metastasis.
10.Advances in clinical diagnosis and treatment of radiation enteritis
Chenying MA ; Jing ZHAO ; Xiaoting XU ; Songbing QIN ; Juying ZHOU
Journal of International Oncology 2023;50(1):28-32
Small bowel capsule endoscopy and double-balloon enteroscopy have become new methods for clinical diagnosis of radiation enteritis (RE) , especially for abnormal intestinal tissue. Targeted biopsy or interventional therapy is expected to achieve precision treatment of RE. The screening of molecular markers in biological samples has also become a new direction for RE diagnosis. Fecal microbiota transplantation has become one of the promising treatments for RE. In addition, mechanism studies based on traditional Chinese medicine, targeted cell death, and omics analysis provide rich strategies for the diagnosis and treatment of RE.