Establishing a 4D-CT lung function related volumetric dose model to reduce radiation pneumonia.

In order to study how to use pulmonary functional imaging obtained through 4D-CT fusion for radiotherapy planning, and transform traditional dose volume parameters into functional dose volume parameters, a functional dose volume parameter model that may reduce level 2 and above radiation pneumonia was obtained. 41 pulmonary tumor patients who underwent 4D-CT in our department from 2020 to 2023 were included. MIM Software (MIM 7.0.7; MIM Software Inc., Cleveland, OH, USA) was used to register adjacent phase CT images in the 4D-CT series. The three-dimensional displacement vector of CT pixels was obtained when changing from one respiratory state to another respiratory state, and this three-dimensional vector was quantitatively analyzed. Thus, a color schematic diagram reflecting the degree of changes in lung CT pixels during the breathing process, namely the distribution of ventilation function strength, is obtained. Finally, this diagram is fused with the localization CT image. Select areas with Jacobi > 1.2 as high lung function areas and outline them as fLung. Import the patient's DVH image again, fuse the lung ventilation image with the localization CT image, and obtain the volume of fLung different doses (V60, V55, V50, V45, V40, V35, V30, V25, V20, V15, V10, V5). Analyze the functional dose volume parameters related to the risk of level 2 and above radiation pneumonia using R language and create a predictive model. By using stepwise regression and optimal subset method to screen for independent variables V35, V30, V25, V20, V15, and V10, the prediction formula was obtained as follows: Risk = 0.23656-0.13784 * V35 + 0.37445 * V30-0.38317 * V25 + 0.21341 * V20-0.10209 * V15 + 0.03815 * V10. These six independent variables were analyzed using a column chart, and a calibration curve was drawn using the calibrate function. It was found that the Bias corrected line and the Apparent line were very close to the Ideal line, The consistency between the predicted value and the actual value is very good. By using the ROC function to plot the ROC curve and calculating the area under the curve: 0.8475, 95% CI 0.7237-0.9713, it can also be determined that the accuracy of the model is very high. In addition, we also used Lasso method and random forest method to filter out independent variables with different results, but the calibration curve drawn by the calibration function confirmed poor prediction performance. The function dose volume parameters V35, V30, V25, V20, V15, and V10 obtained through 4D-CT are key factors affecting radiation pneumonia. Establishing a predictive model can provide more accurate lung restriction basis for clinical radiotherapy planning.

Network pharmacology in combination with bibliometrics analysis on the mechanism of compound Kushen injection in the treatment of radiation pneumonia and lung cancer.

Radiation pneumonia is a common adverse reaction during radiotherapy in lung cancer patients, which negatively impacts the quality of life and survival of patients. Recent studies have shown that compound Kushen injection (CKI), a traditional Chinese medicine (TCM), has great anti-inflammatory and anticancer potential, but the mechanism is still unclear. We used CiteSpace, the R package "bibliometrix," and VOSviewers to perform a bibliometrics analysis of 162 articles included from the Web of Science core collection. A network pharmacology-based approach was used to screen effective compounds, screen and predict target genes, analyze biological functions and pathways, and construct regulatory networks and protein interaction networks. Molecular docking experiments were used to identify the affinity of key compounds and core target. The literature metrology analysis revealed that over 90% of the CKI-related studies were conducted by Chinese scholars and institutions, with a predominant focus on tumors, while research on radiation pneumonia remained limited. Our investigation identified 60 active ingredients of CKI, 292 genes associated with radiation pneumonia, 533 genes linked to lung cancer, and 37 common targets of CKI in the treatment of both radiation pneumonia and lung cancer. These core potential targets were found to be significantly associated with the OS of lung cancer patients, and the key compounds exhibited a good docking affinity with these targets. Additionally, GO and KEGG enrichment analysis highlighted that the bioinformatics annotation of these common genes mainly involved ubiquitin protein ligase binding, cytokine receptor binding, and the PI3K/Akt signaling pathway. Our study revealed that the main active components of CKI, primarily quercetin, luteolin, and naringin, might act on major core targets, including AKT1, PTGS2, and PPARG, and further regulated key signaling pathways such as the PI3K/Akt pathway, thereby playing a crucial role in the treatment of radiation pneumonia and lung cancer. Moreover, this study had a certain promotional effect on further clinical application and provided a theoretical basis for subsequent experimental research.

The Effects of Boron Neutron Capture Therapy on the Lungs in Recurrent Breast Cancer Treatment.

Boron neutron capture therapy (BNCT) has predominantly been performed for brain tumors or head and neck cancers. Although BNCT is known to be applicable to breast cancer, it has only been performed in a few cases involving thoracic region irradiation with reactor-based BNCT systems. Thus, there are very few reports on the effects of BNCT on the thoracic region and no reports of BNCT for breast cancer with accelerator-based BNCT systems. This paper introduces the world's first clinical study employing an accelerator-based BNCT system targeting recurrent breast cancer after radiation therapy. We aim to assess the efficacy and safety of BNCT, focusing on the dose response in the thoracic region, especially concerning the potential for radiation pneumonitis. Preliminary findings from the first three cases indicate no evidence of radiation pneumonitis within three months post treatment. This study not only establishes a foundation for novel breast cancer treatment options but also contributes significantly to the field of BNCT in the thoracic region.

Radiation pneumonia predictive model for radiotherapy in esophageal carcinoma patients.

BACKGROUND: The machine learning models with dose factors and the deep learning models with dose distribution matrix have been used to building lung toxics models for radiotherapy and achieve promising results. However, few studies have integrated clinical features into deep learning models. This study aimed to explore the role of three-dimension dose distribution and clinical features in predicting radiation pneumonitis (RP) in esophageal cancer patients after radiotherapy and designed a new hybrid deep learning network to predict the incidence of RP. METHODS: A total of 105 esophageal cancer patients previously treated with radiotherapy were enrolled in this study. The three-dimension (3D) dose distributions within the lung were extracted from the treatment planning system, converted into 3D matrixes and used as inputs to predict RP with ResNet. In total, 15 clinical factors were normalized and converted into one-dimension (1D) matrixes. A new prediction model (HybridNet) was then built based on a hybrid deep learning network, which combined 3D ResNet18 and 1D convolution layers. Machine learning-based prediction models, which use the traditional dosiomic factors with and without the clinical factors as inputs, were also constructed and their predictive performance compared with that of HybridNet using tenfold cross validation. Accuracy and area under the receiver operator characteristic curve (AUC) were used to evaluate the model effect. DeLong test was used to compare the prediction results of the models. RESULTS: The deep learning-based model achieved superior prediction results compared with machine learning-based models. ResNet performed best in the group that only considered dose factors (accuracy, 0.78 ± 0.05; AUC, 0.82 ± 0.25), whereas HybridNet performed best in the group that considered both dose factors and clinical factors (accuracy, 0.85 ± 0.13; AUC, 0.91 ± 0.09). HybridNet had higher accuracy than that of Resnet (p = 0.009). CONCLUSION: Based on prediction results, the proposed HybridNet model could predict RP in esophageal cancer patients after radiotherapy with significantly higher accuracy, suggesting its potential as a useful tool for clinical decision-making. This study demonstrated that the information in dose distribution is worth further exploration, and combining multiple types of features contributes to predict radiotherapy response.

Liposome-anchored mesenchymal stem cells for radiation pneumonia/fibrosis treatment.

The effectiveness of mesenchymal stem cells (MSCs) on inflammation-related disease is limited and the pharmaceutical preparation that was used to enhance the efficacy of MSCs cannot reach the diseased tissue in large quantities. Herein, antioxidant liposome (Lipo-OPC) is designed to anchor onto the surface of MSCs membrane via click chemical reaction (MSC-Lipo-OPC) without affecting the viability and physiological characteristics of MSCs, thus allowing efficient accumulation of MSC-Lipo-OPC in X-ray irradiated lung sites. More importantly, MSC-Lipo-OPC promotes the change of the quantity and polarity of innate immunocytes, mainly including neutrophils, macrophages and Tregs, in favor of anti-inflammatory, finally preventing the formation of radioactive pulmonary fibrosis. Therefore, it could enhance the treatment outcome of both of MSCs and drugs to radiation-induced lung injury via modifying the drug-loaded nanoparticle on the surface of MSCs membrane, further promoting the application of MSCs in radiation damage and protection.

Toxic Effects of Volume-modulated Arc Therapy for Esophageal Squamous Cell Cancer: Preliminary Clinical Results.

BACKGROUND/AIM: To evaluate the toxic effects associated with various factors, including the presence or absence of concurrent chemotherapy with volume-modulated arc therapy (VMAT) and dose parameters for esophageal cancer (EC), and to assess the safety and feasibility of the VMAT protocol. PATIENTS AND METHODS: Patients with EC who received definitive VMAT between December 2016 and December 2020 were retrospectively analyzed. VMAT plans were designed to deliver 60 Gy to the primary tumor, 54 Gy to high-risk sites, and 51.3 Gy to regional lymph node sites. Toxic effects were evaluated for esophagitis, neutropenia, esophageal stricture, pericardial effusion, radiation-associated pneumonia. RESULTS: Forty-five patients received concurrent chemoradiotherapy (CCRT), while 29 were treated with radiation therapy (RT) alone. The following grade 3 complications were detected: Neutropenia in four patients (5.4%), esophagitis in two (2.7%), and esophageal stricture in one (1.4%). Grade 4 or more complications were not observed. The median age of the CCRT group (67 years) was significantly lower than that of the RT-alone group (77 years) (p<0.0001). The incidence of esophagitis was significantly higher in the CCRT group (75.5%) than in the RT group (48.3%) (p=0.033). The univariate analysis identified increasing mean dose to the pericardium as a significant risk factor for pericardial effusion, and CCRT and performance status ≥1 as significant for radiation-associated pneumonia. These factors were not significant in the multivariate analysis. Neutropenia and esophageal stricture were not associated with any factor examined. CONCLUSION: VMAT alone and in CCRT performed with our protocol was safe and feasible in patients with esophageal squamous cell cancer.

Effect of thoracic radiotherapy dose on the prognosis of advanced lung adenocarcinoma harboring EGFR mutations.

BACKGROUND: The aim of this study was to investigate the effects of different thoracic radiotherapy doses on OS and incidence of radiation pneumonia which may provide some basis for optimizing the comprehensive treatment scheme of these patients with advanced EGFR mutant lung adenocarcinoma. METHODS: Data from 111 patients with EGFR-mutant lung adenocarcinoma who received thoracic radiotherapy were included in this retrospective study. Overall survival (OS) was the primary endpoints of the study. Kaplan-Meier method was used for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate analyses to determine the prognostic factors related to the disease. RESULTS: The mOS rates of the patients, who received radiotherapy dose scheme of less than 50 Gy, 50-60 Gy (including 50 Gy), and 60 Gy or more were 29.1 months, 34.4 months, and 51.0 months, respectively (log-rank P = 0.011). Although trend suggested a higher levels of pneumonia cases with increasing radiation doses, these lack statistical significance (χ2 = 1.331; P = 0.514). The multivariate analysis showed that the thoracic radiotherapy dose schemes were independently associated with the improved OS of patients (adjusted hazard ratio [HR], 0.606; 95% CI, 0.382 to 0.961; P = 0.033). CONCLUSIONS: For the patients with advanced EGFR-mutant lung adenocarcinoma, the radical thoracic radiotherapy dose scheme (≥ 60 Gy) could significantly prolong the OS of patients during the whole course management.

An analysis of the treatment effect of two modes of oxygenation on patients with radiation pneumonia complicated by respiratory failure.

BACKGROUND: Stereotactic radiotherapy (SBRT) is widely used in the treatment of thoracic cancer. OBJECTIVE: To evaluate the efficacy of a non-rebreather mask (NRBM) and high-flow nasal cannula (HFNC) in patients with radiation pneumonia complicated with respiratory failure. METHODS: This was a single-center randomized controlled study. Patients admitted to the EICU of the Fourth Hospital of Hebei Medical University were selected and divided into NRBM and HFNC group. Arterial blood gas analysis, tidal volume, respiratory rates and the cases of patients receiving invasive assisted ventilation were collected at 0, 4, 8, 12, 24, 48, and 72 h after admission. RESULTS: (1) The PaO2/FiO2, respiratory rates, and tidal volume between the two groups at 0, 4, 8, 12, 24, 48, and 72 h were different, with F values of 258.177, 294.121, and 134.372, all P< 0.01. These indicators were different under two modes of oxygenation, with F values of 40.671, 168.742, and 55.353, all P< 0.01, also varied with time, with an F value of 7.480, 9.115, and 12.165, all P< 0.01. (2) The incidence of trachea intubation within 72 h between HFNC and NRBM groups (23 [37.1%] vs. 34 [54.0%], P< 0.05). The transition time to mechanical ventilation in the HFNC and NRBM groups (55.3 ± 3.2 h vs. 45.9 ± 3.6 h, P< 0.05). (3) The risk of intubation in patients with an APACHE-II score > 23 was 2.557 times than score ⩽ 23, and the risk of intubation in the NRBM group was 1.948 times more than the HFNC group (P< 0.05). CONCLUSION: Compared with the NRBM, HFNC can improve the oxygenation state of patients with radiation pneumonia complicated with respiratory failure in a short time, and reduce the incidence of trachea intubation within 72 h.

Corrigendum: Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis-Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy.

[This corrects the article DOI: 10.3389/fonc.2021.650764.].

Exploring the Pharmacological Mechanism of Radix Salvia Miltiorrhizae in the Treatment of Radiation Pneumonia by Using Network Pharmacology.

BACKGROUND: Radiation pneumonia (RP) is the most common complication of radiotherapy to the thorax and seriously affects the survival rate and quality of life of patients. Radix Salviae Miltiorrhizae (RSM) is an ancient Chinese medicine, whose main pharmacological effect is to promote blood circulation and remove stasis. A growing number of studies have proved that RSM has a good effect on RP. However, the underlying mechanism is still unclear and needs to be fully elucidated. METHODS: The effective components and predictive targets of RSM were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of RP were predicted by GeneCards database. The common targets of the two targets mentioned above were analyzed by protein-protein interaction on the STRING website, GO and KEGG analysis on the DAVID website, visualization by CytoScape3.7.0, and screening for Hubber gene by cytoHubber plug-in. RESULTS: A search of the TCMSP database revealed that RSM contains 65 chemical constituents and 165 potential protein targets. A total of 2,162 protein targets were found to be associated with RP. The top 10 hub genes were obtained by MCC algorithm for 70 common genes, including TP53, CASP3, MAPK1, JUN, VEGFA, STAT3, PTGS2, IL6, AKT1, and FOS. By analyzing the Gene Ontology, The anti-radiation pneumonia effect of RSM is that it performs molecular functions (protein homodimerization activity) in the nucleus through three biological processes (positive regulation of transcription from RNA polymerase II promoter,Extrinsic apoptotic signaling pathway in absence of ligand and lipopolysaccharide-mediated signaling pathway). Through KEGG analysis, the mechanism of RSM treatment of radiation pneumonia may be through PI3K-Akt, HIF-1, TNF signaling pathways. CONCLUSIONS: Through network pharmacology analysis, we found the possible target genes of RSM on RP and revealed the most likely signaling pathway, providing theoretical basis for further elucidating the potential mechanism of RSM on RP.

Construction and Verification of a Radiation Pneumonia Prediction Model Based on Multiple Parameters.

OBJECTIVE: Patients with lung cancer are at risk of radiation pneumonia (RP) after receiving radiotherapy. We established a prediction model according to the critical indicators extracted from radiation pneumonia patients. MATERIALS AND METHODS: 74 radiation pneumonia patients were involved in the training set. Firstly, the clinical data, hematological and radiation dose parameters of the 74 patients were screened by Logistics regression univariate analysis according to the level of radiation pneumonia. Next, Stepwise regression analysis was utilized to construct the regression model. Then, the influence of continuous variables on RP was tested by smoothing function. Finally, the model was externally verified by 30 patients in validation set and visualized by R code. RESULTS: In the training set, there was 40 patients suffered≥ level 2 acute radiation pneumonia. Clinical data (diabetes), blood indexes (lymphocyte percentage, basophil percentage, platelet count) and radiation dose (V15 > 40%, V20 > 30%, V35 >18%, V40 > 15%) were related to radiation pneumonia (P < 0.05). Particularly, stepwise regression analysis indicated that the history of diabetes, the basophils percentage, platelet count and V20 could be the best combination used for predicting radiation pneumonia. The column chart was obtained by fitting the regression model with the combined indicator. The receiver operating characteristic (ROC) curve showed that the AUC in the development term was 0.853, the AUC was 0.656 in the validation term. And calibration curves of both groups showed the high stability in efficiently diagnostic. Furthermore, the DCA curve showed that the model had a satisfactory positive net benefit. CONCLUSION: The combination of the basophils percentage, platelet count and V20 is available to build a predictive model of radiation pneumonia for patients with advanced lung cancer.

Analysis of related factors of radiation pneumonia caused by precise radiotherapy of esophageal cancer based on random forest algorithm.

The precise radiotherapy of esophageal cancer may cause different degrees of radiation damage for lung tissues and cause radioactive pneumonia. However, the occurrence of radioactive pneumonia is related to many factors. To further clarify the correlation between the occurrence of radioactive pneumonia and related factors, a random forest model was used to build a risk prediction model for patients with esophageal cancer undergoing radiotherapy. In this study, we retrospectively reviewed 118 patients with esophageal cancer confirmed by pathology in our hospital. The health characteristics and related parameters of all patients were analyzed, and the predictive effect of radiation pneumonia was discussed using the random forest algorithm. After treatment, 71 patients developed radioactive pneumonia (60.17%). In univariate analyses, age, planning target volume length, Karnofsky performance score (KPS), pulmonary emphysema, with or without chemotherapy, and the ratio of planning target volume to planning gross tumor volume (PTV/PGTV) in mediastinum were significantly associated with radioactive pneumonia (P < 0.05 for each comparison). Multivariate analysis revealed that with or without pulmonary emphysema (OR = 7.491, P = 0.001), PTV/PGTV (OR = 0.205, P = 0.007), and KPS (OR = 0.251, P = 0.011) were independent predictors for radiation pneumonia. The results concluded that the analysis of radiation pneumonia-related factors based on the random forest algorithm could build a mathematical prediction model for the easily obtained data. This algorithm also could effectively analyze the risk factors of radiation pneumonia and formulate the appropriate treatment plan for esophageal cancer.

Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis-Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy.

Purpose: To assess the relationship between different doses of radiation and lung density changes and to determine the ability of this correlation to identify esophageal cancer (EC) patients who develop radiation pneumonitis (RP) and the occurrence time of RP. Methods: A planning computed tomography (CT) scan and a re-planning CT scan were retrospectively collected under institutional review board approval for each of 103 thoracic segment EC patients who underwent radiotherapy (RT). The isodose curve was established on the planning CT with an interval of 5 Gy, which was used as the standard for dividing different gradient doses. Planning CT and re-planning CT scans were matched and the mean lung CT value (HU) between different doses gradients was automatically obtained by the software system. The density change value (ΔHU) was the difference of CT value between each dose gradient before and after treatment. The correlation between ΔHU and the corresponding dose was calculated, as well as the regression coefficients. Additionally the correlation between ΔHU and the occurrence and time of RP (< 4 weeks, 4-12 weeks, > 12 weeks) was calculated. Results: The radiation dose and ΔHU was positively correlated, but the correlation coefficient and regression coefficient were lower, 0.261 (P <0.001) and 0.127 (P <0.001), respectively. With the increase of radiation dose gradient, ΔHU in RP≥2 group was higher than that in RP<2 group, and there was significant difference between two groups in ΔHU20-25, ΔHU25-30, ΔHU30-35, ΔHU35-40, ΔHU40-45, ΔHU45-50 (p<0.05). The occurrence time of RP was negatively correlated with the degree of ΔHU (P<0.05), with a high correlation coefficient (Y = week actual value -0.521, P < 0.001) (Y = week grade value -0.381, P = 0.004) and regression coefficient (Y = week actual value -0.503, P<0.001) (Y = week rating value -0.401, P=0.002). Conclusions: A relationship between radiation dose and lung density changes was observed. For most dose intervals, there was an increase of ΔHU with an increased radiation dose, although low correlation coefficient. ΔHU were obvious after irradiation with dose ≥20 Gy which was closely related to the occurrence of RP. For patients with RP, the more obvious ΔHU, the earlier the occurrence of RP, there was a significant negative correlation between them.

Effects of diabetes on the development of radiation pneumonitis.

Radiation pneumonia (RP) is a common adverse reaction to radiation therapy in patients with chest tumors. Recent studies have shown that diabetes mellitus (DM), which can cause systemic multisystem damage, specifically targets lungs, and the incidence of RP in patients with a history of diabetes is higher than that in other patients with tumors who have undergone radiotherapy. DM is an important risk factor for RP in tumor patients undergoing RT, and patients with DM should be treated with caution. This article reviews research on the clinical aspects, as well as the mechanism, of the effects of diabetes on RP and suggests future research needed to reduce RP.

Gut Microbiota-Derived PGF2α Fights against Radiation-Induced Lung Toxicity through the MAPK/NF-κB Pathway.

Radiation pneumonia is a common and intractable side effect associated with radiotherapy for chest cancer and involves oxidative stress damage and inflammation, prematurely halting the remedy and reducing the life quality of patients. However, the therapeutic options for the complication have yielded disappointing results in clinical application. Here, we report an effective avenue for fighting against radiation pneumonia. Faecal microbiota transplantation (FMT) reduced radiation pneumonia, scavenged oxidative stress and improved lung function in mouse models. Local chest irradiation shifted the gut bacterial taxonomic proportions, which were preserved by FMT. The level of gut microbiota-derived PGF2α decreased following irradiation but increased after FMT. Experimental mice with PGF2α replenishment, via an oral route, exhibited accumulated PGF2α in faecal pellets, peripheral blood and lung tissues, resulting in the attenuation of inflammatory status of the lung and amelioration of lung respiratory function following local chest irradiation. PGF2α activated the FP/MAPK/NF-κB axis to promote cell proliferation and inhibit apoptosis with radiation challenge; silencing MAPK attenuated the protective effect of PGF2α on radiation-challenged lung cells. Together, our findings pave the way for the clinical treatment of radiotherapy-associated complications and underpin PGF2α as a gut microbiota-produced metabolite.

Experimental research progress of genetically modified mesenchymal stem cells in the treatment of radiation-induced lung injury / 中华放射医学与防护杂志

Radiation-induced lung injury is a common complication of thoracic malignant tumor radiotherapy and severe nuclear accident injury. Currently, there is no effective treatment on this injury. Mesenchymal stem cells (MSCs) are a group of cells with multi-directional differentiation potential and they can protect lung tissue from radiation damage by homing to the injured site and differentiating to the damaged tissues, secreting cytokines and immune regulation. Further, the genetically modifying mesenchymal stem cells have not only the main characteristics of MSCs, but also can efficiently and stably express or knock down a certain of target genes, thereby enhancing or reducing the sensitivity of mesenchymal stem cells to various physiological stimulus and enhancing its therapeutic effect in radiation-induced lung injury, providing new ideas and new strategies for clinical treatment. This paper reviewed the relevant research progress in recent years.

Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma.

BACKGROUND/AIM: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. PATIENTS AND METHODS: One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. RESULTS: There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. CONCLUSION: The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia.

The Fatty Acid Amide Hydrolase Inhibitor URB937 Ameliorates Radiation-Induced Lung Injury in a Mouse Model.

Radiation-induced lung injury (RILI) is a potentially life-threatening complication of radiotherapy. In the current study, we examined the potential protective effects of URB937, an inhibitor of fatty acid amide hydrolase using a mouse model of RILI. Briefly, male C57BL/6 mice received 16Gy irradiation to the thoracic region and then intraperitoneal injection of either URB937 (1 mg/kg) or vehicle every 2 days for 30 days. The extent of the lung injury was evaluated histologically at the end of the drug treatment as well as 3 months after the cessation of the treatment. The data showed URB937 attenuated radiation-induced lung injury and increased endocannabinoid concentration in lung tissue. Treatment with URB937 decreased leukocyte migration and inflammatory cytokines in bronchoalveolar lavage fluid and plasma at day 30. Histopathological examination revealed URB937 could restore lung structure and restrain inflammatory cell and fibroblast accumulation caused by irradiation in lung tissue. URB937 also decreased radiation-induced pro-inflammatory (e.g., interleukin-1ß, interleukin-6, tumor necrosis factor-α) and pro-fibrotic cytokines (e.g., transforming growth factor-ß1) level in lung tissue, as well as lipid peroxidation in the lungs. Mouse survival examined in a separate group of experimental subjects indicated that URB937 could prolong animal survival. Experiments using a mouse bearing Lewis lung carcinoma cells showed that URB937 does not affect irradiation-induced inhibition of tumor growth. These results suggest that inhibiting fatty acid amide hydrolase could ameliorate RILI without compromising the efficacy of irradiation on tumor control.

Intervention of Progressive Stage of Radiation Pneumonia with Tibetan Medicine Flos Saussureae Plus Glucocorticoid / 广州中医药大学学报

Objective To study the therapeutic effect of Tibetan medicine Flos Saussureae combined with glucocorticoid for progressive stage of radiation pneumonia.Methods A total of 65 post-chemotherapy radiation pneumonia patients with esophageal carcinoma were randomized into western medicine group(20 cases),combined group (21 cases) and Flos Saussureae group (24 cases),which were treated with prednisone (1 mg/kg,orally),prednisone (0.5 mg/kg,orally) plus Flos Saussureae Injection (2 mL/d,by intramuscular injection),and Flos Saussureae Injection (4 mL/d,by intramuscular injection) respectively.The medication lasted for 6 weeks.Before and after treatment,we investigated the scores of chest high resolution CT(HRCT),Leicester Cough Questionnaire (LCQ) scores,6-minute walk distance,pulmonary function indexes of vital capacity (VC),total lung capacity (TLC) and diffusion function DLco,and arterial oxygen partial pressure(PO2).Results (1) The scores of HRCT,6-minute walk distance and LCQ scores of the combined group were improved as compared with those of western medicine group and Flos Saussureae group (P ＜ 0.05).The improvement of psychological scores,social function scores and overall socres of LCQ in Flos Saussureae group was superior to that in western medicine group (P ＜0.05).(2)After treatment,pulmonary function indexes and PO2 of the combined group and Flos Saussureae group were improved compared with those of western medicine group (P ＜ 0.05),and the improvement of DLco and PO2 of the combined group was superior to that of Flos Saussureae group (P＜ 0.05).Conclusion Flos Saussureae Injection combined with glucocorticoid exerts certain therapeutic effect for progressive stage of radiation pneumonia,and large-dose Flos Saussureae Injection is beneficial to the improvement of symptoms and imaging features of the patients.

Experimental study on the protective effect of lentivirus-mediated SIRT6 overexpression on radioactive lung injury in rats / 中国生化药物杂志

Objective To investigate the protective effect of lentivirus-mediated silencing information regulation protein 6(SIRT6)overexpression on radioactive lung injury in rats.Methods 72 male 150-200 g Wistar rats were randomly divided into three groups(n=24).The 6 MV-X-ray linear accelerator was used to irradiate the lungs.The rats in each group were injected with normal saline(TNF-α)were measured at 1, 2, 4, and 8 weeks after radiotherapy(Lent-SIRT6), and the levels of tumor necrosis factor-α(TNF-IL-6 and IL-1β were measured by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.Results The alveolar wall and alveolar stroma were normal in the control group.The alveolar wall of the irradiated group was thickened and fibrosis, and a large number of hypertrophic fibrous tissues were found in the alveolar stroma.The alveolar wall of Lent-SIRT6 group was thickened And alveolar stromal fibrosis symptoms were lighter than the irradiation group.Compared with the control group, the levels of serum TNF-α and IL-6, neutrophil count and the levels of TNF-α, IL-6 and IL-1β in the liver tissue were significantly higher than those in the control group (P<0.05).The lentiviruses overexpressing SIRT6 could alleviate the abnormalities caused by radiation (P<0.05).The difference was statistically significant (P<0.05).Conclusion SIRT6 can effectively inhibit the inflammatory reaction, reduce the lung injury symptoms of radiation pneumonia, and have some protective and prevention effect on lung injury.