Experimental research of pulmonary injury on irradiation combined with pemetrexed

Objective: The aim of our study was to examine whether irradiation combined with pemetrexed can exacerbate pulmonary injury. Methods: Two groups of male Wister Rats were subjected to bilateral apex of lungs irradiation(a single dose of 12 Gy), with or without pemetrexed(20 mg/kg) by intraperitoneal injection at the same time; a third group of weightand age- matched animals were treated with pemetrexed alone, as the same dose scheme, time and root of injection. The fourth group served as control. The whole lung mounts were dissected to histological evaluation, while serum cytokine transforming growth factor-β1(TGF-β1) analysis were compared at 1, 7, 21, 35, 49 days post-irradiation after irradiation. Results: Histological examination showed a thickening of alveolar septal, accumulation of inflammatory cells. The irradiation treatment group and the radiation-chemo treatment group showed a statistically significant higher level of TGF-β1(P < 0.05) than other two groups, but there were no differences between these two irradiation groups. Conclusion: These results demonstrated that pemetrexed can not aggravate pulmonary injury and it could be safely used in concurrent or sequential radio-chemotherapy in lung adenocarcinoma.

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.

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.

Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-B^ret/ret mice

Background:Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage(SAH).However,pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes.Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks,we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH.Methods:In our experiments,platelet-derived growth factor B(PDGF-B)retention motif knockout(PDGF-Bret/ret)mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression.Neurological score,SAH grade,hematoxylin-eosin staining,and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery,as well as western blotting and immunofluorescence staining for underlying molecular expressions.Results:We found that neonatal PDGF-Bret/ret mice exhibited pulmonary atelectasis 12 h after birth.Further investigation showed a decrease in PaO2/FiO2 and lung-specific surfactant proteins in adult PDGF-Bret/ret mice.These dysfunctions were much worse than those in wild-type mice at 24 h after SAH.PDGF-B overexpression alleviated pulmonary dysfunction after SAH.Conclusions:These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH.Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.

Neutrophil depletion-but not prevention of Kupffer cell activation-decreases the severity of cerulein-induced acute pancreatitis

AIM： To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis. METHODS： Nice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride （GdCh） to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. Myeloperoxidases （MPO） assessed neutrophil infiltration. Interleukin-6 （IL-6） and IL-10 were measured in serum, pancreas, lungs and liver. RESULTS： In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCh had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects. CONCLUSION： Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.

Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure

Background Pulmonary thromboendarterectomy （PTE） has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension （CTEPH）. This study aimed to characterize if pulmonary oligemia maneuver （POM） can alleviate pulmonary artery injury during PTE procedure. Methods A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure. They were retrospectively classified as non-POM group （group A, n=55） or POM group （group B, n=57）. Members from group B received POM during rewarming period, whereas members from group A did not. Results There were three （5.45%） early deaths in group A, no death in group B （0） （Fisher＇s exact test, P=0.118）. Six patients in group A needed extracorporeal membrane oxygenation （ECMO） as life support after the PTE procedure, no patients in group B needed ECMO （Fisher＇s exact test, P=0.013）. The patients in group B had a shorter intubation and ICU stay, lower mean pulmonary arterial pressure （mPAP） and pulmonary vascular resistance （PVR）, higher partial pressure of oxygen in artery （PaO2） and arterial oxygen saturation （SaO2） and less medical expenditure than patients in group A. With a mean follow-up time of （58.3 ± 30.6） months, two patients in group A and one patient in group B died. The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance. Three months post the PTE procedure, the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance （P=0.393）. Conclusion POM can alleviate pulmonary artery injury, shorten ICU stay and intubation time, and lower down the rate of ECMO after PTE procedure.

Pulmonary artery injury management during pulmonary thromboendarterectomy

Pulmonary thromboendarterectomy （PEA） is the recommended treatment for chronic thromboembolic pulmonary hypertension （CTEPH）.1 Pulmonary artery injury is a major risk factor during PEA performed at less experienced surgical centers and is associated with adverse short-term consequences.In-hospital mortality may be as high as 15% in some PEA case series,with pulmonary artery injury and persistent pulmonary hypertension as the principal etiologies.2 Many techniques have been used to prevent pulmonary artery injury during PEA,but once the injury occurs,the prognosis is poor and may even result in death.Out of 202 PEA procedures performed at our surgical center,we successfully managed two cases of severe pulmonary artery injury and report our experience in the present case series.Keywords：chronic thromboembolic pulmonary hypertension; pulmonary thromboendarterectomy; pulmonary artery injury