Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Modeling Mediated Crossover Acute and Subacute Damage to the Pulmonary System During Systemic (Subcutaneous) Administration of Bleomycin in Mice to Test the Potential Therapeutic Effect of Polyphenols / Modelado del Daño Agudo y Subagudo Cruzado Mediado al Sistema Pulmonar Durante la Infección Sistémica (Subcutánea) de Administración de Bleomicina a Ratones para Probar el Posible Efecto Terapéutico de los Polifenoles

SUMMARY: The potential anti-inflammatory and antifibrotic activity of polyphenolic extracts of blueberry and grape was evaluated in a mouse model of lung damage induced by subcutaneous administration of bleomycin. The results of testing the polyphenolic extracts on two different systemic administration variants of bleomycin (intraperitoneal and subcutaneous) were compared. It was found that regardless of the method of bleomycin administration, indirect cross-acute and subacute damage to the pulmonary system was observed. Both patterns exhibited the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice resulted in a significant decrease in theseverity of acute and subacute patterns of lung damage, suggesting their protective properties for the microcirculatory bed and a pronounced anti-inflammatory effect.

La potencial actividad antiinflamatoria y antifibrótica de los extractos polifenólicos de arándano y uva se evaluó en un modelo de daño pulmonar en ratón inducido por la administración subcutánea de bleomicina. Se compararon los resultados de las pruebas de los extractos polifenólicos en dos variantes diferentes de administración sistémica de bleomicina (intraperitoneal y subcutánea). Se encontró que, independientemente del método de administración de bleomicina, se observaba daño indirecto cruzado, agudo y subagudo al sistema pulmonar. Ambos patrones exhibieron la misma prevalencia y gravedad. La administración de extractos polifenólicos de arándano y uva a ratones dio como resultado una disminución significativa en la gravedad de los patrones agudos y subagudos de daño pulmonar, lo que sugiere sus propiedades protectoras del lecho micro- circulatorio y un efecto antiinflamatorio pronunciado.

Hérnia torácica traumática associada a laceração de lobo pulmonarcaudal em cão / Traumatic thoracic hernia associated with laceration of the caudal lung lobe in a dog

Traumas torácicos são comuns em pacientes traumatizados e incluem principalmente contusão pulmonar, laceração pulmonar, pneumotórax, hemotórax, fraturas de costela e esterno e hérnia diafragmática. As principais causas são acidentes automobilísticos, quedas e mordeduras. Taquipneia ou dispneia são possíveis sinais clínicos, associados a choque hipovolêmico e sinais gastrointestinais. Lesões torácicas podem ser negligenciadas quando lesões distrativas, como fratura de membros, estão presentes. Assim, o exame clínico minucioso é obrigatório e os animais com insuficiência respiratória podem necessitar de estabilização e cirurgia de emergência. Considerando a importância do trauma torácico na prática clínica, o objetivo deste manuscrito é relatar o caso de hérnia espúria torácica associada a laceração traumática de lobo pulmonar caudal em uma cadela apresentando dispneia intensa após trauma automobilístico. Após uma avaliação emergencial e exames radiográficos, foi diagnosticado tórax instável, fraturas de costelas, contusão pulmonar e pneumotórax grave. Após estabilização clínica, foi realizado tratamento cirúrgico para estabilização do tórax instável. Durante a cirurgia, observou-se herniação e laceração do lobo caudal esquerdo do pulmão, sendo realizadas suturas para correção da laceração pulmonar e estabilização do gradil costal, além da toracostomia para controle do pneumotórax. Nos casos de tórax instável e encarceramento lobar, o tratamento cirúrgico é fundamental, como realizado neste caso, com o objetivo de reparar e reposicionar o lobo pulmonar e estabilizar o tórax instável. A herniação pulmonar traumática é um possível diagnóstico diferencial no tórax instável pós-traumático, assim como a reparação do lobo e a estabilização das costelas por meio de suturas são técnicas eficazes de tratamento cirúrgico.

Thoracic traumas are common in trauma patients and mainly include pulmonary contusion, pulmonary laceration, pneumothorax, hemothorax, rib and sternum fractures and diaphragmatic hernia. The main causes are car accidents, falls and bites. Tachypnea or dyspnea are possible clinical signs, associated with hypovolemic shock and gastrointestinal signs. Thoracic injuries may be overlooked when distracting injuries, such as limb fractures, are present. Thus, thorough clinical examination is mandatory and animals with respiratory failure may require stabilization and emergency surgery. Considering the importance of thoracic trauma in clinical practice, the manuscript aimed to report the case of spurious thoracic hernia associated with traumatic laceration of the caudal lung lobe in a bitch with severe dyspnea after car trauma. After an emergency evaluation and radiographic examinations, a flail chest, rib fractures, pulmonary contusion and severe pneumothorax were diagnosed. After clinical stabilization, surgical treatment was performed to stabilize the flail chest. During surgery, herniation and laceration of the left caudal lobe of the lung were observed, and sutures were performed to correct the pulmonary laceration and stabilize the rib cage, in addition to thoracostomy to control the pneumothorax. In cases of flail chest and lobar entrapment, surgical treatment is essential, as in this case, with the aim of repairing and repositioning the pulmonary lobe and stabilizing the flail chest. Traumatic pulmonary herniation is a possible differential diagnosis in post-traumatic flail chest, as well as repairing the lobe and stabilizing the ribs using sutures are effective surgical treatment techniques.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

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.

A case of corrosive digestive tract and lung injury caused by ingestion of pipeline dredging agent / 中华劳动卫生职业病杂志

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.

Guiqi Yiyuan Ointment protects rat left lung from bystander effect of right lung injury induced by ~(12)C~(6+) beam / 中国中药杂志

This study observed the effects of Guiqi Yiyuan Ointment(GQYY) on the left lung subjecting to bystander effect of right lung injury induced by ~(12)C~(6+) beam in rats and decipher the underlying mechanism from NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteinyl aspartate specific proteinase-1(caspase-1) pathway. Wistar rats were randomized into 7 groups: blank, model, inhibitor [200 mg·kg~(-1), N-acetylcysteine(NAC)], western drug [140 mg·kg~(-1) amifostine(AMI)], and high-, medium-, and low-dose(4.8, 2.4, and 1.2 g·kg~(-1), respectively) GQYY groups. The model of bystander effect damage was established by 4 Gy ~(12)C~(6+) beam irradiation of the right lung(with the other part shielded by a lead plate). The pathological changes in the lung tissue, the level of reactive oxygen species(ROS) in the lung tissue, and the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in the serum were observed and measured in each group. Furthermore, the mRNA and protein levels of NLRP3, ASC, caspase-1, and phosphorylated nuclear factor-κB p65(p-NF-κB p65)/nuclear factor-κB p65(NF-κB p65) were determined. Compared with the blank group, the model group showed thickened alveolar wall, narrowed alveolar cavity, and presence of massive red blood cells and inflammatory infiltration in the alveolar wall and alveolar cavity. In addition, the model group showed elevated ROS levels in both left and right lungs, elevated MDA level, lowered SOD level, and up-regulated mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. Compared with the model group, the drug administration in all the groups reduced inflammatory cell infiltration in the lung tissue. The inhibitor group and the western drug group showed enlarged alveolar cavity, thinned interstitium, and reduced inflammation. There was a small amount of alveolar wall rupture in the high-and medium-dose GQYY groups and reduced inflammatory cell infiltration in the low dose GQYY group. Compared with the model group, drug administration lowered level of ROS in the left and right lungs, lowered the MDA level, elevated the SOD level, and down-regulated the mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. GQYY can effectively reduce the damage caused by radiation and bystander effect, which may be associated with the ROS-mediated NLRP3 inflammasome activation.

Research on the mechanism of mechanical ventilation induced endoplasmic reticulum stress promoting mechanical ventilation-induced pulmonary fibrosis / 中华危重病急救医学

OBJECTIVE@#To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process.@*METHODS@#The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis.@*RESULTS@#Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/β-actin: 1.40±0.02 vs. 1, BIP/β-actin: 2.79±0.07 vs. 1, PDI/β-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/β-actin: 0.53±0.03 vs. 1.40±0.02, BIP/β-actin: 1.73±0.15 vs. 2.79±0.07, PDI/β-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group.@*CONCLUSIONS@#MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.

Evaluating the effect of montelukast tablets on respiratory complications in patients following blunt chest wall trauma: A double-blind, randomized clinical trial / 中华创伤杂志(英文版)

PURPOSE@#Patients with multiple traumas are at high risk of developing respiratory complications, including pneumonia and acute respiratory distress syndrome. Many pulmonary complications are associated with systemic inflammation and pulmonary neutrophilic infiltration. Leukotriene-receptor antagonists are anti-inflammatory and anti-oxidant drugs subsiding airway inflammation. The present study investigates the effectiveness of montelukast in reducing pulmonary complications among trauma patients.@*METHODS@#This randomized, double-blind, placebo-control trial was conducted in patients with multiple blunt traumas and evidence of lung contusion detected via CT scan. We excluded patients if they met at least one of the following conditions: < 16 years old, history of cardiopulmonary diseases or positive history of montelukast-induced hypersensitivity reactions. Patients were allocated to the treatment (10 mg of montelukast) or placebo group using permuted block randomization method. The primary measured outcome was the volume of pulmonary contusion at the end of the trial. The secondary outcomes were intensive care unit and hospital length of stay, ventilation days, multi-organ failure, and the in-hospital mortality rate.@*RESULTS@#In total, 65 eligible patients (treatment = 31, placebo = 34) were included for the final analysis. The treatment group had more pulmonary contusion volume (mean (SD), mm3) at the right (68726.97 (93656.54) vs. 59730.27 (76551.74)) and the left side (67501.71 (91514.04) vs. 46502.21 (80604.21)), higher initial C-reactive peptide level (12.16 (10.58) vs. 10.85 (17.87)) compared to the placebo group, but the differences were not statistically significant (p > 0.05). At the end of the study, the mean (SD) of pulmonary contusion volume (mm3) (right side = 116748.74 (361705.12), left side = 64522.03 (117266.17)) of the treatment group were comparable to that of the placebo group (right side = 40051.26 (64081.56), left side = 25929.12 (47417.13), p = 0.228 and 0.082, respectively). Moreover, both groups have statistically similar hospital (mean (SD), days) (10.87 (9.83) vs. 13.05 (10.12)) and intensive care unit length of stays (mean (SD), days) (7.16 (8.15) vs. 7.82 (7.48)). Of note, the frequency of the in-hospital complications (treatment vs. control group) including acute respiratory distress syndrome (12.9% vs. 8.8%, p = 0.71), pneumonia (19.4% vs. 17.6%, p = 0.85), multi-organ failure (12.9% vs. 17.6%, p = 0.58) and the mortality rate (22.6% vs. 14.7%, p = 0.41) were comparable between the groups.@*CONCLUSION@#Administrating montelukast has no preventive or therapeutic effects on lung contusion or its complications.

Kiwi fruit essence reduces radiation-induced lung injury by down-regulating TNF-α and PDGF-B in rats / 细胞与分子免疫学杂志

Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediated protection of radiation-induced lung injury (RILI) in rats. Methods 96 male healthy Sprague-Dawley rats were divided into normal control group, model group, and kiwi fruit essence treatment group(60 and 240 mg/kg) by the random number table method, with 24 animals in each group. The whole lungs underwent 6 MV X-ray irradiation (18 Gy) to induce RILI animal models in rats of the latter three groups. On the next day after irradiation, rats in the latter two groups were intragastrically administrated with 60 or 240 mg/kg kiwi fruit essence, once a day. The rats in the normal control and model groups were treated with 9 g/L sodium chloride solution. Eight rats in the latter three groups were randomly sacrificed on days 14, 28, and 56, while normal control rats were sacrificed on day 56 as the overall control. Blood samples were collected and separated. Serum concentrations of TNF-α and PDGF-B were detected using ELISA. The lung tissues were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg kiwi fruit essence group significantly reduced alveolitis on days 14 and 28 as well as PF lesions on days 28 and 56. Compared with the normal control group, HYP content in the lung tissue of the model group increased on day 28 and day 56, while TNF-α and PDGF-B levels in the serum and lung tissues increased at each time point. Compared with the model group during the same period, 60 and 240 mg/kg kiwi fruit essence element treatment group reported the diminished levels of serum and pulmonary TNF-α on day 14 and day 28. Consistently, the lung tissue HYP content and serum and pulmonary PDGF-B levels on day 28 and day 56 were reduced. In addition, the above indicators in the 240 mg/kg kiwi fruit essence treatment group were lower than those for the 60 mg/kg kiwi fruit essence treatment group. Conclusion Kiwi fruit essence can alleviate RILI in rats, which is related to the down-regulation of TNF-α expression at the early stage and decreased PDGF-B level at the middle and late stages.

Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter / 中华创伤杂志(英文版)

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.

Electrotaxis of alveolar epithelial cells in direct-current electric fields / 中华创伤杂志(英文版)

PURPOSE@#This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.@*METHODS@#AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis.@*RESULTS@#The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.@*CONCLUSION@#EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Research Progress on the Protective Effect of Intestinal Flora on Radiation-induced Lung Injury in Thoracic Tumors / 中国肺癌杂志

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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Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome / 中南大学学报(医学版)

OBJECTIVES@#Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism.@*METHODS@#Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting.@*RESULTS@#Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD.@*CONCLUSIONS@#Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

Effect and mechanism of amphiregulin on acute respiratory distress syndrome in mice / 中华危重病急救医学

OBJECTIVE@#To explore the protective effect of amphiregulin (Areg) on acute respiratory distress syndrome (ARDS) in mice and its underlying mechanism.@*METHODS@#(1) Male C57BL/6 mice aged 6-8 weeks were selected for animal experiments and divided into 3 groups (n = 10) according to the random number table method, which includes sham-operated group (Sham group), ARDS model group [ARDS model in mice was established by intratracheal instillation of lipopolysaccharide (LPS) 3 mg/kg] and ARDS+Areg intervention group [recombinant mice Areg (rmAreg) 5 μg was injected intraperitoneally 1 hour after LPS modeling]. The mice were sacrificed at 24 h after LPS injection lung histopathological changes were observed under hematoxylin-eosin (HE) staining and scored for lung injury; oxygenation index and wet/dry ratio of lung tissue were measured; the content of protein in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid (BCA) method, the level of inflammatory factors interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). (2) Mice alveolar epithelial cell line MLE12 cells were obtained and cultured for experiment in vitro. Blank control group (Control group), LPS group (LPS 1 mg/L) and LPS+Areg group (rmAreg 50 μg/L was added 1 hour after LPS stimulation) were set. The cells and culture fluid were collected at 24 hours after LPS stimulation, and the apoptosis level of MLE12 cells was detected by flow cytometry; the activation level of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and the expressions of apoptosis-related proteins Bcl-2 and Bax in MLE12 cells were detected by Western blotting.@*RESULTS@#(1) Animal experiments: compared with the Sham group, the lung tissue structure of ARDS model group was destroyed, the lung injury score was significantly increased, the oxygenation index was significantly decreased, the wet/dry weight ratio of lung was significantly increased, and the levels of protein and inflammatory factors in BALF were significantly increased. Compared with ARDS model group, lung tissue structure damage was reduced, pulmonary interstitial congestion, edema and inflammatory cell infiltration were significantly reduced, and lung injury score was significantly decreased (scores: 0.467±0.031 vs. 0.690±0.034) in ARDS+Areg intervention group. In addition, oxygenation index in ARDS+Areg intervention group was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 380.00±22.36 vs. 154.00±20.74]. Lung wet/dry weight ratio (5.40±0.26 vs. 6.63±0.25), protein and inflammatory factors levels in BALF [protein (g/L): 0.42±0.04 vs. 0.86±0.05, IL-1β (ng/L): 30.00±2.00 vs. 40.00±3.65, IL-6 (ng/L): 190.00±20.30 vs. 581.30±45.76, TNF-α (ng/L): 30.00±3.65 vs. 77.00±4.16], and the differences were statistically significant (all P < 0.01). (2) Cell experiments: compared with the Control group, the number of apoptotic MLE12 cells was significantly increased in the LPS group, and the levels of PI3K phosphorylation, anti-apoptotic gene Bcl-2 level and pro-apoptotic gene Bax level were increased in MLE12 cells. Compared with the LPS group, the number of apoptosis in MLE12 cells was significantly reduced in the LPS+Areg group after administration of rmAreg treatment [(17.51±2.12)% vs. (36.35±2.84)%], and the levels of PI3K/AKT phosphorylation and Bcl-2 expression in MLE12 cells were significantly increased (p-PI3K/PI3K: 2.400±0.200 vs. 0.550±0.066, p-AKT/AKT: 1.647±0.103 vs. 0.573±0.101, Bcl-2/GAPDH: 0.773±0.061 vs. 0.343±0.071), and Bax expression was significantly suppressed (Bax/GAPDH: 0.810±0.095 vs. 2.400±0.200). The differences were statistically significant (all P < 0.01).@*CONCLUSIONS@#Areg could alleviate ARDS in mice by inhibiting the apoptosis of alveolar epithelial cells through activating PI3K/AKT pathway.

Uso prolongado de cánula nasal de alto flujo en niños con problemas respiratorios / Prolonged use of high flow nasal cannula in children with respiratory problems

La cánula nasal de alto flujo (CNAF) es una modalidad ventilatoria no invasiva segura y efectiva, usada ampliamente en patología respiratoria aguda en adultos y niños. Objetivo: presentar casos clínicos pediátricos que utilizaron CNAF por tiempo prolongado por problemas respiratorios crónicos. Descripción de casos clínicos, revisión de fichas clínicas de 5 pacientes que utilizaron CNAF por más de 1 mes, entre los años 2017-2020 en el Complejo Asistencial Dr. Sótero del Río. Aprobado por Comité de Ética. Resultados: 5 pacientes varones de mediana 61 (44 a 212) días de edad al inicio del uso de CNAF. Diagnóstico de base: displasia broncopulmonar (2/5), síndrome de Treacher Collins (1/5), síndrome de cimitarra con hipoplasia pulmonar derecha (1/5) y traqueobroncomalacia severa (1/5). Todos requirieron previamente uso de ventilación invasiva o no invasiva con mediana de 59 (4 a 78) días. A todos se les realizó broncoscopia, saturometría contínua o poligrafía para diagnóstico y titulación de CNAF y oxígeno. Todos mejoraron clínicamente, la SpO2 y el número de apneas. Dos pacientes se enviaron a domicilio con uso de Airvo2 nocturno. La mediana de uso de CNAF fue 165 (34 a 445) días. Conclusiones: el uso prolongado de CNAF es útil en pacientes pediátricos seleccionados, bien tolerado y factible de utilizar en domicilio.

The high-flow nasal cannula (HFNC) is a safe and effective non-invasive ventilation support widely used in acute respiratory pathology in adults and children. Objective: To present pediatric clinical cases that used HFNC for an extended period due to chronic respiratory disease. Description of clinical cases, review of medical records of 5 patients who used HFNC for more than 1 month, between the years 2017-2020 at Complejo Asistencial Dr. Sótero del Río. Approved by the Ethics Committee. Results: 5 male patients with a median age of 61 (44 to 212) days at the start of HFNC use. Underlying diagnoses: bronchopulmonary dysplasia (2/5), Treacher Collins syndrome (1/5), Scimitar syndrome with right pulmonary hypoplasia (1/5), and severe tracheobronchomalacia (1/5). All of them previously required invasive or non-invasive ventilation for a median of 59 (4 to 78) days. All patients underwent bronchoscopy, continuous pulse oximetry or polygraphy for diagnosis and titration of HFNC and oxygen. All showed clinical improvement, including SpO2 levels and the number of apneas. Two patients were discharged with nocturnal use of Airvo 2 at home. The median duration of HFNC use was 165 (34 to 445) days. Conclusions: Prolonged use of HFNC is useful in selected pediatric patients, well tolerated, and feasible for home use.

Pulmonary involvement from animal toxins: the cellular mechanisms

Venomous animals and their venom have always been of human interest because, despite species differences, coevolution has made them capable of targeting key physiological components of our bodies. Respiratory failure from lung injury is one of the serious consequences of envenomation, and the underlying mechanisms are rarely discussed. This review aims to demonstrate how toxins affect the pulmonary system through various biological pathways. Herein, we propose the common underlying cellular mechanisms of toxin-induced lung injury: interference with normal cell function and integrity, disruption of normal vascular function, and provocation of excessive inflammation. Viperid snakebites are the leading cause of envenomation-induced lung injury, followed by other terrestrial venomous animals such as scorpions, spiders, and centipedes. Marine species, particularly jellyfish, can also inflict such injury. Common pulmonary manifestations include pulmonary edema, pulmonary hemorrhage, and exudative infiltration. Severe envenomation can result in acute respiratory distress syndrome. Pulmonary involvement suggests severe envenomation, thus recognizing these mechanisms and manifestations can aid physicians in providing appropriate treatment.(AU)

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Neumatocele traumático: una presentación inusual del trauma cerrado de tórax en paciente de 21 años / Traumatic pneumatocele: an unusual presentation of blunt chest trauma in a 21-year-old patient

El neumatocele traumático, o pseudoquiste pulmonar traumático, es una complicación infrecuente del trauma cerrado de tórax, caracterizada por lesiones cavitadas únicas o múltiples de paredes fibrosas bien delimitadas, sin revestimiento epitelial. Representa un reto diagnóstico ante la prevalencia de etiologías más frecuentes de cavitación pulmonar, presentación clínica inespecífica y el carácter subreportado de la patología. Se presenta el caso de un paciente de 21 años, con cuadro clínico de fiebre y dolor torácico posterior a traumatismo contuso por accidente en motocicleta, con identificación de una lesión cavitada rodeada de vidrio esmerilado, ubicada en lóbulo superior derecho en tomografía de tórax. Se ofreció tratamiento antibiótico ante la sospecha clínica de sobreinfección. Sin embargo, se atribuyó la alteración pseudoquística pulmonar al antecedente traumático. En ocasiones las cavitaciones pulmonares postrauma no son identificadas en la atención inicial, por ende, es fundamental la evaluación clínica e imagenológica subsecuente.

Traumatic pneumatocele, or traumatic pulmonary pseudocyst, is a rare complication of blunt chest trauma, characterized by multiple or unique cavitary lesions, with well-defined fibrous walls without epithelial lining. It represents a diagnostic challenge due to the higher prevalence of other etiologies of lung cavities, nonspecific clinical features and the under-reported nature of this pathology. We present the case of a 21-year-old male with fever and chest pain after a blunt chest trauma in a motorcycle accident, with identification of a cavity in the right upper lobe, surrounded by ground glass opacities. Antibiotic therapy was administered after clinical suspicion of superinfection, however, the cavitary lesion was attributed to the trauma. Occasionally, traumatic pulmonary pseudocysts are not identified during initial assessment, therefore, clinical and imagenologic follow-up is essential.

Vivência de fisioterapeutas com pacientes hospitalizados sob oxigenoterapia / Experience of physiotherapists with hospitalized patients under oxygen therapy

Objetivo: este estudo objetivou conhecer a vivência de fisioterapeutas com pacientes hospitalizados sob oxigenoterapia, bem como identificar os desafios vivenciados durante a sua intervenção. Métodos: trata-se de um estudo quantitativo e transversal, realizado no período de setembro de 2021 a março de 2022, com fisioterapeutas atuantes em hospitais da cidade de Fortaleza-CE. A coleta de dados foi realizada de forma presencial e virtual pela plataforma Google Forms, por meio de um questionário com perguntas objetivas sobre vivência, intervenção e desafios durante assistência ao paciente sob oxigenoterapia. Os dados coletados foram armazenados no Microsoft Excel® 2010 e analisados pelo SPSS® versão 20.0, utilizando-se de estatística descritiva. Resultados: participaram do estudo 101 fisioterapeutas, 76,2% do gênero feminino, e 45,5% dos participantes eram graduados há 5 anos. Destes, 83,2% dos fisioterapeutas afirmaram que SpO2 < 90% é indicativo de oxigenoterapia. A maioria (79,2%) discordou da utilização da máscara de Venturi para pacientes com Covid-19 e apontou a cânula nasal de alto fluxo (39,6%) e a máscara reservatório não reinalante (40,6%) como as mais utilizadas. Entre os desafios enfrentados durante a assistência, a interação com a equipe interdisciplinar (25,70%), o desmame da oxigenoterapia (21,80%) e a indisponibilidade de recursos (20,80%) foram os mais relatados. Conclusão: grande parte dos profissionais atua indicando o oxigênio suplementar em situações em que há SaO2 < 90%, realizando avaliação à beira leito da cânula nasal de alto fluxo por meio do índice ROX e indicando intervenção fisioterapêutica.

Objective: this study aimed to understand the experience of physiotherapists with patients hospitalized under oxygen therapy, as well as to identify the challenges experienced during their intervention. Methods: it was a quantitative and cross-sectional study conducted from September 2021 to March 2022, with physiotherapists working in hospitals in Fortaleza-CE. Data collection was performed in person and virtually through the Google Forms platform, through a questionnaire with objective questions about experience, intervention, and challenges during care to patients under oxygen therapy. The collected data were stored in Microsoft Excel® 2010 and analyzed by SPSS® version 20.0, using descriptive statistics. Results: the study included 101 physical therapists, 76.2% female, and 45.5% of the participants had graduated for five years. Of these, 83.2% of physical therapists stated that SpO2 < 90% is indicative of oxygen therapy. The majority (79.2%) disagreed with the use of the venturi mask for patients with Covid-19 and pointed to the high-flow nasal cannula (39.6%) and the non-reinlantreservoir mask (40.6%) as the most used. Among the challenges faced during care, interaction with the interdisciplinary team (25.70%), weaning from oxygen therapy (21.80%), and unavailability of resources (20.80%) was the most reported. Conclusion: most professionals indicate supplemental oxygen in situations where SaO2 < 90%, perform an evaluation at the bedside of the high-flow nasal cannula from the ROX index and suggest physiotherapeutic intervention.

Levantamento de dados de condenações pulmonares por aspiração de sangue em abate de suínos sob o Serviço de Inspeção Estadual da Bahia entre os anos de 2018 a 2020 / Data Survey on pulmonary condemnatios for blood aspiration in swine slaughter under the Bahia State, Brazil Inspection Service from 2018 to 2020

O presente estudo tem como objetivo descrever os dados das condenações de pulmões por aspiração de sangue em abate de suínos do estado da Bahia, no período de janeiro de 2018 a outubro de 2020, em abatedouros sob fiscalização do Serviço de Inspeção Estadual (SIE). A coleta retrospectiva foi facilitada pela Agência de Defesa Agropecuária da Bahia (ADAB), através da Guia de Trânsito Animal (GTA), e foram coletados dados de 255.834 suínos abatidos em matadouros frigoríficos, localizados em oito municípios. Nos anos de 2018 e 2019, a aspiração de sangue foi a lesão mais encontrada. Em 2018, foram 15,45% (1131/7322) das alterações macroscópicas e 36,48% (1131/3100) das condenações pulmonares, e em 2019, foram 14,75% (1053/7138) e 36,20% (1053/2909), respectivamente. A congestão foi a lesão mais encontrada em 2020, mas não houve diferença considerável com a aspiração de sangue, que foi destaque das condenações pulmonares, com 38,07% (712/1870). Estes dados revelam a frequência de condenação por aspiração de sangue no estado da Bahia e sugerem implementação de treinamentos de manejo não violento para os funcionários dos abatedouros frigoríficos, visto que esse tipo de lesão indica estresse e uma tecnopatia associada à falha na insensibilização e sangria, em razão do animal agonizar enquanto tenta respirar após a incisão no pescoço.

This study aims to analyze data on lung condemnations for blood aspiration in pig slaughter in the state of Bahia, Brazil from january 2018 to october 2020, in slaughterhouses under supervision of the State Inspection Service (SIE). The retrospective collection was facilitated by the Agricultural Defense Agency of Bahia (ADAB), through the Animal Transit Guide (GTA), and data were collected from 255,834 pigs slaughtered in slaughter houses located in eight municipalities. In 2018 and 2019, blood aspiration was the most common lesion. In 2018, it was 15,45% (1131/7322) of macroscopic changes and 36,48% (1131/3100) of lung condemnations, and in 2019, it was 14,75% (1053/7138) and 36,20% (1053/2909), respectively. Congestion was the most common lesion found in 2020, but there was no considerable difference with blood aspiration, which was highlighted in pulmonary condemnations, with 38,07% (712/1870). These data reveal the frequency of condemnations for blood aspiration in the state of Bahia, Brazil and suggest the implementation of training in non-violent management for employees of slaughterhouses, as this type of injury indicates stress and a technopathy as sociated with failure in stunning and bleeding, because the animal agonizes while trying to breathe after the neck incision