Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Radiotherapy, Intensity-Modulated/methods* ; Retrospective Studies ; Lung Injury ; Radiotherapy Dosage ; Radiation Injuries/epidemiology* ; Esophagitis/epidemiology* ; Risk Factors ; Pulmonary Disease, Chronic Obstructive/complications*

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Radiation therapy is one of the main treatment methods for patients with thoracic malignant tumors, which can effectively improve the survival rate of the patients. However, radiation therapy can also cause damage to normal tissues while treating tumors, leading to radiation-induced lung injury such as radiation pneumonia and pulmonary fibrosis. Radiation-induced lung injury is a complex pathophysiological process involving many factors, and its prevention and treatment is one of the difficult problems in the field of radiation medicine. Therefore, the search for sensitive predictors of radiation-induced lung injury can guide clinical radiotherapy and reduce the incidence of radiation-induced lung injury. With the in-depth study of intestinal flora, it can drive immune cells or metabolites to reach lung tissue through the circulatory system to play a role, and participate in the occurrence, development and treatment of lung diseases. At present, there are few studies on intestinal flora and radiation-induced lung injury. Therefore, this paper will comprehensively elaborate the interaction between intestinal flora and radiation-induced lung injury, so as to provide a new direction and strategy for studying the protective effect of intestinal flora on radiation-induced lung injury.
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Humans ; Lung Injury/prevention & control* ; Gastrointestinal Microbiome ; Lung Neoplasms/radiotherapy* ; Lung/pathology* ; Radiation Injuries/metabolism* ; Thoracic Neoplasms

Objective: To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances. Methods: Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology. Results: Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( < 0.05 or < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% . 17.8% and 10.0%, < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups. Conclusions The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.
Animals ; Biomechanical Phenomena ; Blast Injuries ; etiology ; pathology ; Disease Models, Animal ; Explosions ; Lung Injury ; etiology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.
Animals ; Apoptosis ; Caspase 12 ; Caspase 3 ; metabolism ; Creatine Kinase, MB Form ; blood ; Endoplasmic Reticulum Stress ; Heart Injuries ; physiopathology ; Heat-Shock Proteins ; metabolism ; L-Lactate Dehydrogenase ; blood ; Lung ; pathology ; MAP Kinase Kinase 4 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myocardium ; pathology ; Random Allocation ; Reperfusion Injury ; Transcription Factor CHOP ; metabolism

OBJECTIVETo observe the effect of intrapartum and postpartum factors on abnormal neurological findings in the extremely preterm infants.

METHODClinical data of 62 premature infants (33 of male, 29 of female) were retrospectively analyzed. None of the premature infants had birth defect; their gestational ages were all less than 28 weeks (23(+ 6)-27(+ 6) weeks). They were hospitalized within 12 hours after birth in the neonatal intensive care unit (NICU) of BAYI Children's Hospital from November 2010 to June 2013. The blood gas, birth condition, complications, the mechanical ventilation and the ultrasonic encephalography were recorded. The 62 cases were divided into 2 groups, alive group and died group. Meanwhile, all cases of survial were divided into brain injuries group and normal brain group. Data were analyzed with t-test, Chi square test and Spearman correlation analysis.

RESULTFifty-six cases were alive, and 6 cases died (3 were during the treatment and 3 were after parents gave up). The average birth weight of brain injuries group was (954 ± 182) g; and that of the normal brain group was (1 071 ± 136) g. There were significant differences between the two groups in gender (χ(2) = 4.314, P = 0.038), gestational age (χ(2) = 11.622, P = 0.001), birth weight (t = 2.728, P = 0.009), which had significant correlation with neurological outcomes. The Spearman correlative coefficients were -0.278, 0.456 and 0.364 respectively. And P values were 0.038, 0.000 and 0.006. The rates of multiple pregnancy, lung hemorrhage and surgical operation in brain injuries group were 45%(9/20), 55%(11/20), 40%(8/20), which were significantly higher than those in normal brain group, 3%(1/36), 17%(6/36), 11%(4/36)(χ(2) = 12.800, 8.936, 4.773, P all < 0.05). These three factors were the high risk factors for adverse neurological outcomes, the odds ratios were 28.64, 6.11 and 5.33 respectively. There was no significant difference in delivery mode, amniotic fluid, maternal infection, asphyxia, necrotizing enterocolitis, patent ductus arteriosus, sepsis, mechanical ventilation, inhaled nitric oxide therapy, blood glucose, blood gas analysis, doses of dopamine between brain injuries group and normal brain group. The birth weight in alive group was (1 029 ± 163) g, which was significantly higher than those in died group (870 ± 144)g (r=0.29, P=0.022). There was no significant difference in other factors between alive group and died group(P all>0.05).

CONCLUSIONGender, gestational age and birth weight may have relation with the neurological outcomes of extremely preterm infants. Multiple pregnancy, pulmonary hemorrhage and surgical operation are the risk factors of brain injuries. Birth weight is related to the survival of extremely preterm infants.

Birth Weight ; Brain Injuries ; physiopathology ; Female ; Gestational Age ; Humans ; Infant, Extremely Premature ; Infant, Newborn ; Infant, Premature, Diseases ; Lung ; pathology ; Male ; Pregnancy ; Pregnancy, Multiple ; Retrospective Studies ; Risk Factors

OBJECTIVETo observe the effects of docosahexaenoic acid (DHA) on the expressions of TNF-α, IL-6, and leukotriene B4 (LTB4) in serum and expression of NF-κB in pulmonary tissue of rats with severe scald injury.

METHODSOne hundred and sixty SD rats were divided into sham injury (A), sham injury+DHA (B), scald (C), and scald+DHA (D) groups according to the random number table, with 40 rats in each group. Rats in groups A and B were sham injured, while rats in groups C and D were inflicted with 30% TBSA full-thickness scald on the back. Rats in groups B and D were injected with 0.5 mg/mL DHA solution with the dosage of 1 mL/kg via tail vein 5 minutes post injury, while rats in groups A and C with normal saline solution 1 mL/kg. At post injury hour (PIH) 3, 6, 12, 24, and 48, pulmonary tissue and abdominal aorta blood were collected from 8 rats in each group. The serum levels of TNF-α, IL-6, and LTB4 were determined with ELISA, and the protein expression of NF-κB p65 in pulmonary tissue was determined with Western blotting. Data were processed with analysis of variance of factorial design and LSD-t test.

RESULTS(1) The serum levels of TNF-α and IL-6 of rats in group A were similar to those of group B at each time point (with tTNF-α values from 0.223 to 0.947, tIL-6 values from 0.767 to 2.084, P values above 0.05). Compared with those of group A, the serum levels of TNF-α and IL-6 of rats in groups C and D were significantly higher at each time point (with tTNF-α values from 11.800 to 40.357, tIL-6 values from 10.334 to 39.321, P values below 0.01). The serum levels of TNF-α and IL-6 of rats in group D were significantly lower than those of group C at each time point (with tTNF-α values from -17.643 to -8.331, tIL-6 values from -21.596 to -6.332, P values below 0.01). The serum levels of TNF-α and IL-6 in groups C and D both showed a trend of increase earlier and decrease later, and they peaked at PIH 12, respectively (360.4 ± 13.2), (306.8 ± 7.2) pg/mL and (265.4 ± 12.3), (230.5 ± 2.2) pg/mL. (2) The serum level of LTB4 in group A was similar to that of group B at each time point (with t values from 0.787 to 1.096, P values above 0.05). The serum level of LTB4 was significantly higher in groups C and D than in group A at each time point (with t values from 7.501 to 38.962, P values below 0.01). The serum level of LTB4 in group D was obviously lower than that of group C at each time point (with t values from -19.244 to -2.532, P values below 0.01). The serum level of LTB4 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, (4.59 ± 0.29) and (2.85 ± 0.32) ng/mL respectively. (3) The protein expression of NF-κB p65 in pulmonary tissue in group A was similar to that of group B at each time point (with t values from 0.847 to 1.256, P values above 0.05). The protein expression of NF-κB p65 was significantly higher in groups C and D than in group A at each time point (with t values from 15.167 to 98.074, P values below 0.01). The protein expression of NF-κB p65 in group D was obviously lower than that of group C at each time point (with t values from -37.190 to -14.415, P values below 0.01). The protein expression of NF-κB p65 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, respectively 4.46 ± 0.12 and 2.94 ± 0.21.

CONCLUSIONSParenteral supply of DHA to rats with severe scald injury can reduce the levels of TNF-α, IL-6, and LTB4 in serum and decrease the expression of NF-κB in pulmonary tissue, thus alleviating the inflammation response.

Animals ; Blotting, Western ; Burns ; Cytokines ; Docosahexaenoic Acids ; Enzyme-Linked Immunosorbent Assay ; Inflammation ; Interleukin-6 ; blood ; Leukotriene B4 ; blood ; Lung ; metabolism ; pathology ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum ; Soft Tissue Injuries ; Tumor Necrosis Factor-alpha ; blood ; genetics ; Up-Regulation ; physiology

OBJECTIVE: To compare the expression of tumor necrosis factor-alpha (TNF-alpha) between brain and peripheral organs after cerebral contusion in order to provide the scientific theoretical basis for forensic pathological diagnosis and wound age estimation. METHODS: Brain and peripheral organs including heart, liver, spleen, lung, kidney tissues of 45 SD rats after the cerebral contusion were obtained and TNF-alpha of these tissues were analyzed with immunohistochemistry methods. RESULTS: TNF-alpha was detected at 1 h in brain, reaching maximum at 6 h and 3 d after the cerebral contusion, and then decreased but still kept at high expression level at 7 d. TNF-alpha was detected at 1 h after the cerebral contusion in heart, liver, spleen, lung and kidney tissues. The number of cells expressing TNF-alpha increased gradually, reaching maximum at 3 d after the contusion of brain, and then decreased but still kept at high expression level at 7 d. CONCLUSION Besides the change of cerebral contusion, this study considered both the brain and peripheral organs. It is helpful for forensic pathological diagnosis and wound age estimation after contusion of brain.
Animals ; Brain/metabolism* ; Brain Injuries/pathology* ; Contusions/pathology* ; Disease Models, Animal ; Female ; Immunohistochemistry ; Kidney/metabolism* ; Liver/metabolism* ; Lung/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Spleen/metabolism* ; Tissue Distribution ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVETo explore the clinical and physical factors that might give rise to radiation-induced esophagitis in three-dimensional conformal radiotherapy for non-small cell lung cancer.

METHODSTo collect the clinical and physical records and follow-up information of 106 NSCLC patients without undergoing surgery in our hospital. χ(2) test, linear tendency test and analysis of variance were employed to analyze the relationship between occurrence of radiation-induced esophagitis and clinical and physical treatment. Logistic analysis was also used for multivariate analysis.

RESULTSAmong the 47 cases of radiation-induced esophagitis, 31 cases were of grade I, 11 of grade II, 5 of grade III, and with a total occurrence rate of 44.3% (47/106). Radiation-induced esophagitis was correlated with Karnofsky scores, radiation sensitization and tumor location (χ(2) = 11.30, 8.45, 7.67, P < 0.05). Radiation-induced esophagitis was correlated with the length of irradiated esophagus and average dose of irradiated esophagus (F = 20.82, 83.08, P < 0.001). With the increase of the irradiated volume percentage from V20, V30, V40 up to V50, the occurrence rate of radiation-induced esophagitis was also increased, almost with a linear trend (P < 0.05). Application of all the above factors to logistic model indicated that radiation sensitization,length of irradiated esophagus, average dose and V50 were all statistically significant foactors in the occurrence of radiation-induced esophagitis (OR = 0.321, 2.850, 7.307 and 8.558, P < 0.05).

CONCLUSIONSRadiation sensitization,length of irradiated esophagus, average dose of irradiated esophagus and V50 are independent factors in the occurrence of radiation-induced esophagitis. V50 is of greater importance in the judgement of occurrence of radiation-induced esophagitis.

Aged ; Carcinoma, Non-Small-Cell Lung ; radiotherapy ; Esophagitis ; etiology ; Esophagus ; pathology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; radiotherapy ; Male ; Middle Aged ; Multivariate Analysis ; Radiation Injuries ; etiology ; Radiation Tolerance ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Retrospective Studies

OBJECTIVE: To explore ultra-structural changes of fat embolism syndrome (FES) in the lung. METHODS: Fat embolism animal model was developed by fat intravascular injection to the experimental rabbits. The rabbits were sacrificed after thrombosis immediately (0 h), 3 h, 8 h and 1 d, 2 d, 7 d, 14 d after thrombosis, respectively. Rabbits were injected with the same dose of saline in the control group. All experimental procedures were same in experimental and control groups. The animal model of fat embolism was validated using HE and Sudan III staining. Ultra-structural changes of lung were observed by using transmission electron microscopy. RESULTS: Ultra-structural changes in capillaries and small blood vessels were found in experimental group. Type II alveolar cells, related cells and organelles showed time-dependent changes. Lipid drops and inflammatory cells were not found in control group. Lamellar body did not show emptying phenomenon and the amount of lamellar body was normal. CONCLUSION The study could provide the theoretical principle for fat embolism casesin forensic pathology.
Animals ; Capillaries/ultrastructure* ; Disease Models, Animal ; Embolism, Fat/pathology* ; Epithelial Cells/pathology* ; Forensic Pathology ; Lung/ultrastructure* ; Microscopy, Electron, Transmission ; Pulmonary Embolism/pathology* ; Rabbits ; Staining and Labeling ; Time Factors ; Wounds and Injuries/complications*