The association between double-lumen tube versus bronchial blocker and postoperative pulmonary complications in patients after lung cancer surgery.

Background: Both double-lumen tube (DLT) and bronchial blocker (BB) are used for lung isolation in patients undergoing lung cancer surgery. However, the effects of different devices for lung isolation remain inconclusive. Present study was designed to investigate the association between the choice of the two devices and postoperative pulmonary complications (PPCs) in patients with lung cancer. Methods: In this retrospective cohort study, patients who underwent lung cancer surgery between January 1, 2020 and October 31, 2020 were screened. Patients were divided into two groups according to different devices for lung isolation: DLT group and BB group. Primary outcome was the incidence of a composite of PPCs during postoperative in-hospital stay. Results: A total of 1721 were enrolled for analysis, of them, 868 received DLT and 853 BB. A composite of PPCs was less common in patients with BB (25.1%, [214/853]) than those received DLT (37.9% [329/868] OR 0.582 95% CI 0.461-0.735 P < 0.001). Respiratory infection was less common in BB group (14.4%, [123/853]) than DLT group (30.3%, [263/868], P<0.001). The incidence of non-PPCs complications was not statistically significant between the 2 groups. Conclusions: For patients undergoing surgery for lung cancer, the use of BB for lung isolation was associated with a reduced risk of PPCs when compared with DLT.

A simple method for the formalin fixation of lungs in toxicological pathology studies.

Optimized lung preparation for detailed structural evaluation is required to improve consistency in preclinical safety evaluation, differences of opinion exist among regulatory agency personnel regarding the optimal methods for routine formalin fixation of lungs from rodent toxicology studies. The simple tracheal ligation fixation method emphasizes tracheal ligation before opening the thorax instead of attempting to re-inflate after lung collapse when opening the thorax. Photomicrographs of this method demonstrated an unprecedented ability to maintain the natural lung architecture, in contrast to the unavoidable changes in the alveolar environment by the intratracheal instillation and vascular perfusion methods. In addition, a comparison of fixation methods on lung morphology in a rodent model of LPS-induced acute lung injury demonstrated that the tracheal ligation fixation method may provide a standard approach for morphometry. Additionally, a TUNEL assay was used to determine the degree of autolysis, which revealed that the autolysis was insignificant in the central areas of each lobe of the lung compared to the lung periphery by tracheal ligation fixation. In conclusion, our novel modified method, which avoids the disadvantages of generating artifacts, fulfills the requirement of preserving the clear, natural morphology of the lung making it suitable and worthy of recommendation for toxicological studies in a good laboratory practice (GLP) lab.

[Protective effect of a protease inhibitor on acute lung injury after hepatic ischemia/reperfusion in the rat].

OBJECTIVE: To study the role of a protease inhibitor (ulinastatin) in protection of lung damage following hepatic ischemia/reperfusion in rat. METHODS: Thirty-two healthy male SD rats were randomly divided into four groups (n=8 in each group). Group A was served as sham-injury control group, group B rats were subjected to 90 minutes hepatic ischemia, and group C rats underwent 120 minutes reperfusion after 90 minutes ischemia of the liver. Ulinastatin (UTI) was administered to animals in group D which were reperfused 120 minutes after 90 minutes of ischemia of the liver. In addition to plasma malondialdehyde (MDA), broncho-alveolar lavage fluid protein (BALFP) content, and lung dry-to-wet weight ratios (D/W) were respectively examined in each group. The concentration of myeloperoxidase (MPO) in lung tissue was also measured. RESULTS: Compared to group A, plasma MDA, content of MPO in lung tissues and BALFP were significantly increased in both group B and group C, but they were much lower than those in group D. In addition, D/W was markedly decreased during hepatic ischemia and after 120 minutes reperfusion, while it was significantly increased in animals pretreated with UTI. CONCLUSION: Acute lung injury after hepatic ischemia and reperfusion is mainly induced by the oxidant stress, and neutrophil infiltration in the lung tissues is responsible for the damage under these conditions. Proteases inhibitors such as UTI might have antioxidation effects which attenuate lung injury induced by trauma to remote organs.

Subchronic toxicological study of two artemisinin derivatives in dogs.

The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles.

Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer.

CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its involvement in tumorigenesis is still poorly understood. Here, we report that CUEDC2 is a key regulator of macrophage function and critical for protection against colitis-associated tumorigenesis. CUEDC2 expression is dramatically upregulated during macrophage differentiation, and CUEDC2 deficiency results in excessive production of proinflammatory cytokines. The level of CUEDC2 in macrophages is modulated by miR- 324-5p. We find that Cuedc2 KO mice are more susceptible to dextran-sodium-sulfate-induced colitis, and macrophage transplantation results suggest that the increased susceptibility results from the dysfunction of macrophages lacking CUEDC2. Furthermore, we find that Cuedc2 KO mice are more prone to colitis-associated cancer. Importantly, CUEDC2 expression is almost undetectable in macrophages in human colon cancer, and this decreased CUEDC2 expression is associated with high levels of interleukin-4 and miR-324-5p. Thus, CUEDC2 plays a crucial role in modulating macrophage function and is associated with both colitis and colon tumorigenesis.

Injury of cell tight junctions and changes of actin level in acute lung injury caused by the perfluoroisobutylene exposure and the role of Myosin light chain kinase.

OBJECTIVES: To investigate the injury of cell tight junctions and change in actin level in the alveolus epithelial cells of the lung after perfluoroisobutylene (PFIB) exposure and the role of myosin light chain kinase (MLCK) in the injury. METHODS: Rats and mice were exposed to a sublethal dose of PFIB. The changes in tight junction zonula occludens-1 (ZO-1), actin and myosin light chain kinase (MLCK) were detected by immunofluorescence at 30 min, 1, 2, 4, 8, 16, 24, 48 and 72 h after PFIB exposure. The role of MLCK was analyzed by lung indices and the actin level. RESULTS: The normal ZO-1 immunofluorescence density and those after PFIB exposure were 71.63, 39.41, 37.59, 35.71, 33.22, 31.34, 31.61, 24.51, 40.03 and 44.71 respectively, The normal actin immunofluorescence density and those after PFIB exposure were 31.82, 36.46, 36.57, 41.60, 40.95, 35.41, 30.69, 19.96, 29.30 and 33.00 respectively, The normal MLCK immunofluorescence density and those after PFIB exposure were 61.21, 50.87, 48.37, 43.65, 41.96, 35.44, 31.77, 30.85, 33.10 and 38.20 respectively. When the MLCK inhibitor ML-7 was given in advance, pulmonary edema and actin degradation were suppressed. CONCLUSIONS: At an earlier stage, the increased permeability of the blood-air barrier after PFIB exposure is probably the result of injury of cell tight junctions that acts in concert with later changes in actin, resulting in an increase in permeability. MLCK could be a potential target for novel drug development for relief of acute lung injury.

Cell injuries of the blood-air barrier in acute lung injury caused by perfluoroisobutylene exposure.

OBJECTIVES: To investigate the complete process of cell injuries in the blood-air barrier after perfluoroisobutylene (PFIB) exposure. METHODS: Rats were exposed to PFIB (140 mg/m(3)) for 5 min. The pathological changes were evaluated by lung wet-to-dry weight ratio, total protein concentration of bronchoalveolar lavage fluid and HE stain. Ultrastructural changes were observed by transmission electron microscope. Apoptosis was detected by in situ apoptosis detection. Changes of actin in the lung tissue were evaluated by western blot assay. RESULTS: No significant pulmonary edema or increased permeability was observed within the first 4 h, post PFIB exposure. However, inflammatory cell infiltration and alveolar wall thickening were observed from 2 h. Destruction of the alveoli constitution integrity, edema and protein leakage were observed at 8 h. The injuries culminated at 24 h and then recovered gradually. The ultrastructural injuries of alveolar type I epithelial cells, alveolar type II epithelial cells and pulmonary microvascular endothelial cells were observed at 30 min post PFIB exposure. Some injuries were similar to apoptosis. Compared with control, more serious injuries were observed in PFIB-exposed rats after 30 min. At 8 h, some signs of cell necrosis were observed. The injuries culminated at 24 h and then ameliorated. The number of apoptotic cells abnormally increased at 30 min post PFIB exposure, the maximum appeared at 24 h, and then ameliorated gradually. Western blot analysis revealed that the level of actin in the lung showed no significant changes within the first 4 h post PFIB exposure. However, it decreased at 8 h, reached a nadir at 24 h, and then recovered gradually. CONCLUSIONS: The pathological processes were in progress persistently post PFIB exposure. The early injuries probably were the result of the direct attack of PFIB and the advanced injuries probably arose from the inflammatory reaction induced by PFIB.