Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury

Background Irradiation dose and volume are the major investigated the relationships between the irradiation dose model of graded volume irradiation of the rat lung. physical factors of radiation-induced lung injury. The study and volume in radiation-induced lung injury by setting up a Methods Animals were randomly assigned to three groups. The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume. The treatment plan for the three groups was： group I received a ＂high dose to a small volume＂ （25% volume group） with the mean irradiation volume being 1.748 cm^3 （25% lung volume）; the total dose and mean lung dose （MLD） were 4610 cGy and 2006 cGy, respectively （bilateral AP-PA fields, source to axis distance （SAD） = 100 cm, 6MVX, single irradiation）; Group 2 received a ＂low dose to a large volume＂ （100% volume group） with the mean irradiation volume being 6.99 cm^3 （100% lung volume）; the total dose was 1153 cGy. MLD was 2006 cGy, which was the same as that of group 1 （bilateral AP-PA fields, SAD = 100 cm, 6MVX, single irradiation）; Group 3 was a control group. With the exception of receiving no irradiation, group 3 had rest steps that were the same as those of the experimental groups. After irradiation, functional, histopathological, and CT changes were compared every two weeks till the 16th week. Results Functionally, after irradiation breath rate （BR） increases were observed in both group 1 and group 2, especially during the period of 6th-8th weeks. The changes of BR in the 100% volume group were earlier and faster. For the 25% volume group, although pathology was more severe, hardly any obvious increase in BR was observed. Radiographic changes were observed during the early period （the 4th week） and the most obvious changes manifested during the mediated period （the 8th week）. The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group, and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion, pleural thickening, and lung shrinking. Morphologically, the 100% volume group mainly presented signs of vascular damage, including signs of vascular wall edemas, hypertrophy, and sclerosis. The 25% volume group mainly presented with erythrocyte cell exudation, inflammation, and parenchymal damage. Conclusions The delivery of a small dose of radiation to a large volume is not safe. A low dose smeared out over large volumes, albeit reversible, may lead to fatal respiratory dysfunction. Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose. Clinically, the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin

Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.

TLD calibration and absorbed dose measurement in a radiation-induced liver injury model under a linear accelerator

The application of a thermoluminescent detector(TLD) for dose detection at the liver irradiation site in mice under linear accelerator precision radiotherapy and the use of a single high dose to irradiate the mouse liver to construct a biological model of a radiation-induced liver injury(RILD) in mice were to determine the feasibility of constructing a precision radiotherapy model in small animals under a linear accelerator. A 360° arc volumetric rotational intensity-modulated radiotherapy(VMAT) plan with a prescribed dose of 2 Gy was developed for the planned target volume(PTV) at the location of the TLD within solid water to compare the difference between the measured dose of TLD and the assessed parameters in the TPS system. The TLD was implanted in the livers of mice, and VMAT was planned based on TLD to compare the measured and prescribed doses. C57BL/6 J mice were randomly divided into control and 25-Gy radiation groups and were examined daily for changes in body weight. They were euthanized at 3 and 10 weeks after radiation, and the levels of liver serum enzymes such as alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) were measured to observe any pathological histological changes in the irradiated areas of the mouse liver. The measured values of solid underwater TLD were within ± 3% of the Dmean value of the evaluation parameter in the TPS system. The mice in the 25-Gy radiation group demonstrated pathological signs of radiation-induced liver injury at the site of liver irradiation. The deviation in the measured and prescribed doses of TLD in the mouse liver ranged from-1.5 to 6%;construction of an accurate model of RILD using the VMAT technique under a linear accelerator is feasible.

A novel pulmonary fibrosis murine model with immune-related liver injury

Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.

Rabbit model of radiation-induced lung injury

Objective:To explore the feasibility of establishing an animal model of chronic radiationinduced lung injury.Methods:Twenty-eight New Zealand white rabbits were randomly divided into 3 groups(the right lung irradiation group,the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established b) highdoes radiotherapy in the irradiation groups,then all rabbits underwent CT and pathological examinations at 1.2.4.8.12.16 weeks,respectively after radiation.Results:Within 4 weeks of irradiation,some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At 8-12 weeks after irradiation,CT scanning showed ground glass samples signs,patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Correlation between miR-564, TGF-β1, and radiation-induced lung injury

Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.

Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Radiation-induced brain injury after a conventional dose of intensity-modulated radiotherapy for nasopharyngeal carcinoma:a case report and literature review

A 61-year-old female nasopharyngeal carcinoma patient was admitted to the hospital with sudden cognitive dysfunction one month after Volumetric Intensity Modulated Arc Therapy(VMAT)conventional dose radiotherapy,and the initial diagnosis was radiation-induced brain injury(RBI).After comprehensive treatment with steroid hormones,the patient’s condition rapidly improved.Typically,in nasopharyngeal carcinoma patients treated with VMAT,the incidence of RBI is extremely low when the temporal lobe dose is less than 65 Gy or 1%of the volume is less than 65 Gy.When this limit is exceeded,RBI may occur in varying degrees.However,in this case,even though the temporal lobe dose was under the prescribed limit,the patient still experienced RBI.The rare observations in this case can be used as a reference,and clinicians should seriously consider the possibility of RBI in similar cases.

Time-dependent Changes in CT of Radiation-induced Liver Injury:A Preliminary Study in Gastric Cancer Patients

In this study, the time-dependent changes on dynamic computed tomograph (CT) of radiation-induced liver injury in gastric cancer patients was examined.The CT images of 52 gastric cancer patients who had received chemoradiotherapies were reviewed on the PACS system.Dynamic CT scan was performed in all the subjects.Our results showed that 18 patients were found to have radiation-induced liver injury.The CT findings of radiation-induced liver injury in gastric cancer patients tend to show up one month after radiation treatment.The damaged area was of low density on all three phases, and then it was enhanced on portal vein phase or delay phase.The focal radiation reaction of liver without basic disease vanished 9-11 months later after treatment.We are led to conclude that dynamic CT is of help in the diagnosis of CRT-induced liver injury, and it may be the method of choice for following up the whole course of the CRT-induced liver injury, i.e., form hepatic damage to healing.The classification of CT findings we recommend can avoid the influence of technological factors, and thereby serve as a better guide for treatment of CRT-induced liver injury.

Prevention and treatment of radiation-induced lung injury by hydroxypiperquin phosphate: a clinical and experimental study

Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.

GSN antibody pretreatment aggravates radiation-induced lung injury in mice

Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation therapy.Gelsolin(GSN) is a widespread,multifunctional regulator of cellular structure and metabolism.In this work,the roles of GSN in radiation-induced lung injury in Balb/c mice were studied.The GSN levels in plasma reduced progressively in 72 hours after irradiation,and then increased gradually.GSN contents in the bronchoalveolar lavage(BAL) fluid increased after thoracic irradiation,whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased again.Mice were intravenously injected with 50 ug GSN antibody 0.5 hour before 20 Gy of thoracic irradiation.GSN antibody pretreatment increased lung inflammation,protein concentration in the BAL fluid and leukocytes infiltration in the irradiated mice.The activities of superoxidase dismutase(SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups,whereas the levels of malondialdehyde(MDA)increased.These results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury

BACKGROUND: Cardiac arrest(CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation(ECPR) and conventional cardiopulmonary resuscitation(CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury.METHODS: Sixteen male swine were randomized to CCPR(CCPR;n=8;CCPR alone) and ECPR(ECPR;n=8;extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant(P>0.05), the blood and lung biomarkers were statistically significant(P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant(P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group.CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response postresuscitation.

Alleviation of acute pancreatitis-associated lung injury by inhibiting the p38 mitogen-activated protein kinase pathway in pulmonary microvascular endothelial cells

BACKGROUND Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis(SAP)-related acute lung injury(ALI).Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI.However,the precise mechanism associated with p38 is unclear,particularly in pulmonary microvascular endothelial cell(PMVEC)injury.AIM To determine its role in the tumor necrosis factor-alpha(TNF-α)-induced inflammation and apoptosis of PMVECs in vitro.We then conducted in vivo experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI.METHODS In vitro,PMVEC were transfected with mitogen-activated protein kinase kinase 6(Glu),which constitutively activates p38,and then stimulated with TNF-α.Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels,respectively.In vivo,SAP-ALI was induced by 5%sodium taurocholate and three different doses of SB203580(2.5,5.0 or 10.0 mg/kg)were intraperitoneally injected prior to SAP induction.SAP-ALI was assessed by performing pulmonary histopathology assays,measuring myeloperoxidase activity,conducting arterial blood gas analyses and measuring TNF-α,interleukin(IL)-1βand IL-6 levels.Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration,Evans blue pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2,Bax,Bim and cle-caspase3 levels.The proteins levels of P-p38,NFκB,IκB,P-signal transducer and activator of transcription-3,nuclear factor erythroid 2-related factor 2,HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580.RESULTS In vitro,mitogen-activated protein kinase(Glu)transfection resulted in higher apoptotic rates and cytokine(IL-1βand IL-6)levels in TNF-α-treated PMVECs.In vivo,SB2035080 attenuated lung histopathological injury,decreased inflammatory activity(TNF-α,IL-1β,IL-6 and myeloperoxidase)and preserved pulmonary function.Furthermore,SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration,Evans blue accumulation,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers,apoptosis-related proteins(cle-caspase3,Bim and Bax)and endothelial microstructure.Moreover,SB203580 significantly reduced the pulmonary P-p38,NFκB,P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels.CONCLUSION p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.

Study on pulmonary injury due to acute H_2S inhalation and its therapeutic scheme

Pulmonary injury after acute H2S inhalation was studied with bronchoalveolar lavage（BAL）,ultracentrifuge,and optical and electron microscopy.The changes of the activities oflactate dehydrogenase,alkaline and acid phosphatase,and angiotension converting enzymes inBAL fluid were used as the indicator of cellular damages,those of leucocytic count and the indi-cator of inflammatory response,and those of the concentration of protein and Evans blue as theindicator of vascular permeability.In addition the effects of H2S on lipid peroxidation,naturalantioxidative system and energy substances and the changes of phospholipid concentration inBAL fluid were also observed.The results were as follows:1.Inhalation of H2S exerted a severe cytotoxic effect on the lung tissues resulting in dam-ages on various types of cells and a severe edematogenic effect on lung parenchyma.2.The development of pulmonary edema in H2S intoxication resulted from a combination ofdifferent pathogenic factors.3.The biochemical changes and their recovery occurred earlier than the pathologicalchanges and their recovery.The efficacy of 6 categories of drugs including 25 medicaments against H2S intoxication wasevaluated in mice,and 10 drugs were found to be prophylactically effective.The effects of vari-ous methemoglobin-forming agents and some other drugs were also studied in their treatment ofH2S intoxication in rabbits and dogs.It was concluded that methemoglobin-forming agentscould be used as specific antidotes but could not provent or alleviate the lung damages due toH2S inhalation unless they were administered in association with dexamethasone,vitamin E oranisodamine.A scheme of the medical treatment for H2S intoxication was presented.

Functional changes of pulmonary surfactant in rats with lung injury induced by endotoxin

We studied the functional changes of pulmonary surfactant （PS） in acutelung injury models produced by endotoxin injection (E.coli O55B5) in rats.The sur-face properties of the lung lavage liquid and the total phospholipids （TPL） ex-tracted from it were assessed on a modified Wilhelmy film balance.γ-A isothermof the lavage liquid revealed an increase in minimum surface tension and a de-crease in hysteresis area,recruitment index and stability index,whereas that ofTPL extracted from it did not show any change except for hysteresis area.Thesurface activity correlates positively with the TPL content but negatively with thetotal protein content in the lavage liquid.The findings indicated that there was adysfunction of PS in rats with the lung injury induced by endotoxin,suggestingthat the function deficiency of PS might be caused by decreased phospholipidsand increased proteins in the alveoli.

Effects of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome

BACKGROUND： Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome （ARDS）.METHODS： ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance （NAVA） with a tidal volume （VT） of 6 mL/kg and theelectrical activity of diaphragm （EAdi）-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups： sham operation （SHAM）group （n=5） and bilateral vagotomy （VAG） group （n=5）. Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS： Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation （P〈0.05）. There was no significant difference in PaCO2 betweenthe SHAM and VAG groups （P〉0.05）, and the VAG group had a high VT, peak pressure （Ppeak）,and mean pressure （Pm） compared with the SHAM group 1, 2, 3 hours after ventilation （P〈0.05）.Compared to the SHAM group, dead space fraction （VD/VT） and respiratory system elastance （Ers）in the VAG group increased （P〈0.05） and static pulmonary compliance （Cst） decreased markedly（P〈0.05） after ventilation for 3 hours. Lung wet/dry weight ratio （W/D） （8.4±1.2 vs. 6.6±1.0）, lung injuryscore （6.3±1.8 vs. 3.8±1.3）, tumor necrosis factor-# （TNF-#） （779±372 pg/mL vs. 355±130 pg/mL）and interleukin-8 （IL-8） （169±21 pg/mL vs. 118±17 pg/mL） increased significantly in the VAG groupcompared with the SHAM group （P〈0.05）.CONCLUSION： Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.

Successful Extracorporeal Membranous Oxygenation with Possible Transfusion-Related Acute Lung Injury after Pulmonary Endarterectomy

Transfusion-related acute lung injury (TRALI) is characterized by acute severe hypoxemia with bilateral noncardiogenic pulmonary edema after transfusion of a plasma-containing blood component. In patients undergoing cardiac surgery, the incidence of TRALI is high;however, the detailed clinical course is unknown. Here, we report a case of life-threatening TRALI following pulmonary thrombectomy, which was successfully treated with extracorporeal membranous oxygenation (ECMO).

SARS-COV-2 Induce Pulmonary Injury from Basic to Clinical Research

The SARS-CoV-2 has infected over 194,909,000 cases and over 4,170,000 deaths in the world before the end of July 2021. The virus attacks human alveoli and induces severe lung injury (COVID-19 disease) and spreads rapidly. The mechanisms of COVID-19 disease are unclear. To better understand this disease, This review analyzes the SARS-CoV-2 biological characteristics, insights the effect of alveolar epithelium and its adjacent microvascular endothelium, investigates human host cells immune response and immunothrombosis. Explains clinical manifestations of COVID-19 associated lung injury. It may be helpful for development management strategies for COVID-19 associated pulmonary damage.

Effect of N-acetylcysteine on pulmonary fibrosis, endothelial injury and vasoactive factors in patients with chronic pulmonary heart disease

Objective:To study the effect of N-acetylcysteine on pulmonary fibrosis, endothelial injury and vasoactive factors in patients with chronic pulmonary heart disease.Methods:Patients with COPD complicated by chronic pulmonary heart disease who were treated in Zigong Third People's Hospital between October 2015 and December 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine combined with conventional therapy, and the control group received conventional therapy. Serum levels of pulmonary fibrosis indexes, endothelial injury and oxidative stress injury indexes and vasoactive factors were measured before and after treatment.Results:14 d and 28 d after treatment, serum TGF-β1,β-catenin, uPA, MMP7, ET-1, VEGF, IMD, ADM, MDA, 8-iso-PGF2 and AOPP levels of both groups of patients were significantly lower than those before treatment and serum TGF-β1,β-catenin, uPA, MMP7, ET-1, VEGF, IMD, ADM, MDA, 8-iso-PGF2 and AOPP levels of NAC group were significantly lower than those of control group.Conclusion:N-acetylcysteine can significantly inhibit pulmonary fibrosis, endothelial injury and vasoactive factor secretion in patients with chronic pulmonary heart disease.