Riesgo cardiovascular en pacientes con esclerosis sistémica / Cardiovascular Risk in Patients with Systemic Sclerosis

Introducción: El riesgo cardiovascular es importante en la evaluación de los pacientes con esclerosis sistémica. Objetivo: Determinar el riesgo cardiovascular en pacientes con esclerosis sistémica. Métodos: Se realizó un estudio transversal y descriptivo en pacientes protocolizados del Servicio de Reumatología, en el período de enero 2020 a enero 2022. Se recogieron variables demográficas, clínicas, y se aplicó la calculadora de riesgo cardiovascular Framingham. Resultados: Se incluyeron 105 pacientes con edad media de 48,6 ± 15,3 años, el grupo más frecuente de 50 a 59 años (36,2 por ciento), predominó el sexo femenino 92,2 por ciento el color de piel blanca (74,3 por ciento), el tiempo de evolución fue mayor a 5 años (66,7 por ciento) con una media de 10,5 ± 9,3. El valor promedio de la escala de gravedad modificada de Medsger fue 5,1 ± 2,7 y el 72,4 por ciento con afectación leve. El fenómeno de Raynaud y la fibrosis pulmonar fueron más frecuentes con un 89,5 por ciento y 55,2 por ciento. El índice de Rodnan en promedio fue de 13,1 ± 8,0 y los reactantes de fase aguda normales en la mayoría. Los factores de riesgo cardiovascular más frecuentes fueron la HTA (30,2 por ciento) y dislipidemia (19,9 por ciento). El índice de masa corporal que predominó fue de peso adecuado (54,3 por ciento). Predominó el riesgo cardiovascular bajo según score de Framingham (86 por ciento). Existieron diferencias significativas entre las medias del tiempo de evolución y el riesgo cardiovascular (10 ± 6,9 frente a 9,6 ± 8,8 frente a 16,9 ± 10,8; p = 0,032). Conclusiones: El riesgo cardiovascular en los pacientes con esclerosis sistémica fue bajo(AU)

Introduction: Cardiovascular risk is important in the evaluation of patients with systemic sclerosis. Objective: To determine the cardiovascular risk in patients with systemic sclerosis. Methods: A cross-sectional and descriptive study was carried out in protocolized patients of Rheumatology Service, from January 2020 to January 2022. Demographic and clinical variables were collected, and Framingham cardiovascular risk calculator was used. Results: One hundred five patients were included with a mean age of 48.6 ± 15.3 years, the most frequent group was 50 to 59 years (36.2percent), female sex (92.2percent) predominated, as well as white skin color (74.3percent). The evolution time was greater than 5 years (66.7percent) with a mean of 10.5 ± 9.3. The average value of modified Medsger severity scale was 5.1 ± 2.7 and 72.4percent had mild involvement. Raynaud's phenomenon and pulmonary fibrosis were more common at 89.5percent and 55.2percent. Rodnan index on average was 13.1 ± 8.0 and the acute phase reactants were normal in the majority. The most frequent cardiovascular risk factors were HBP (30.2percent) and dyslipidemia (19.9percent). The predominant body mass index was adequate weight (54.3percent). Low cardiovascular risk according to Framingham score prevailed (86percent). There were significant differences between the mean duration of evolution and cardiovascular risk (10 ± 6.9 vs. 9.6 ± 8.8 vs. 16.9 ± 10.8; p = 0.032). Conclusions: The cardiovascular risk in patients with systemic sclerosis was low(AU)

Toxicidad pulmonar secundaria a bleomicina. Reporte de un caso / Pulmonary Toxicity Secondary to Bleomycin. A Case Report

La toxicidad pulmonar por antineoplásicos es muy variable dependiente del grupo far-macológico; la bleomicina es uno de los medicamentos en los que se ha reportado este evento. Este citostático puede lesionar el endotelio pulmonar y el epitelio alveolar para llevar a un proceso inflamatorio y fibrótico del intersticio con repercusiones potencial-mente fatales.A continuación, se presenta un caso de enfermedad intersticial tipo neumonía organi-zada asociada a bleomicina en un paciente de 68 años con diagnóstico linfoma Hodg-kin clásico de tipo esclerosis nodular, con estudio imagenológico normal previo al tratamiento

Antineoplastic pulmonary toxicity is highly variable depending on the pharmacological group; bleomycin is one of the drugs in which this event has been reported. This cyto-static can injure the pulmonary endothelium and the alveolar epithelium to lead to an in-flammatory and fibrotic process of the interstitium with potentially fatal repercussions. The following is a case of interstitial disease type organizing pneumonia associated with bleomycin in a 68-year-old patient diagnosed with classical Hodgkin lymphoma of nodular sclerosis type, with imaging study prior to normal treatment

Potential antifibrotic effect of blueberry and grape polyphenol extracts in acute and subacute bleomycin-induced lung tissue injury models in mice / Potencial efecto antifibrótico de los extractos de polifenoles de arándano y uva en modelos de lesión tisular pulmonar aguda y subaguda inducida por bleomicina en ratones

SUMMARY: An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Se realizó un estudio experimental morfológico y morfométrico de la función antifibrótica de extractos de arándano y uva en un modelo de lesión pulmonar en ratones inducida por la administración intraperitoneal de bleomicina. Durante la administración intraperitoneal de bleomicina a ratones, se observaron daños agudos y subagudos en el sistema pulmonar. Ambos patrones tuvieron la misma prevalencia y severidad. La administración de extractos polifenólicos de arándano y uva a ratones mostró una reducción significativa en la severidad del patrón agudo y subagudo de lesión pulmonar. Los extractos de arándano y uva reducen la fase aguda del daño a la microvasculatura, mejoran la función fagocítica, tienen un efecto antiinflamatorio, reducen el grado de infiltración linfohistiocítica y los focos locorregionales de efectos inflamatorios residuales.

A case of stage Ⅲ pneumoconiosis with large shadow by burr-like changes misdiagnosed as lung cancer / 中华劳动卫生职业病杂志

Pneumoconiosis is characterized by chronic lung inflammation and fibrosis, and inflammation can promote pulmonary fibrosis, which in turn leads to pneumoconiosis. When a large shadow with a long diameter of not less than 2 cm and a short diameter of not less than 1 cm appears in the lung, it can be classified as stage Ⅲ pneumoconiosis. This paper reports a case of stage Ⅲ pneumoconiosis with a large shadow in the upper right lung accompanied by burr-like changes misdiagnosed as lung cancer by CT examination.When the large shadow lesions in patients with pneumoconiosis and lung cancer are difficult to distinguish on CT, an additional MRI examination, particularly T(2)W imaging sequence is useful sequence for identifying the two.

Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models / 中华劳动卫生职业病杂志

Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type Ⅲ collagen, transforming growth factor-β (TGF-β) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.

Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice / 中华内科杂志

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

Neotuberostemonine and tuberostemonine ameliorate pulmonary fibrosis through suppressing TGF-β and SDF-1 secreted by macrophages and fibroblasts via the PI3K-dependent AKT and ERK pathways / 中国天然药物

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg-1 bleomycin and orally administered with 30 mg·kg-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.

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.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Research progress of anti-fibrotic drugs that inhibit epithelial-mesenchymal transition in pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is the end-stage pathological change of lung diseases, which seriously affects the respiratory function of human body. A large number of studies at home and abroad have confirmed that epithelial-mesenchymal transition (EMT) is an important intermediate stage in the development of pulmonary fibrosis. Inhibition of multiple pathways upstream and downstream of EMT, such as the classical Smads pathway and non-Smads pathway of TGF-1 can effectively inhibit the process of EMT and alleviate pulmonary fibrosis. This article will review the main conclusions of the mechanism of action of EMT as a target to improve the pathology of pulmonary fibrosis so far, and provide a theoretical basis and research direction for further research and development of anti-pulmonary fibrosis drugs.

Research progress of thyroid hormone in pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is end-stage of variety of heterogeneous interstitial lung disease, characterizedby excessive proliferation of fibroblasts and extracellular matrix deposition and destruction of lung parenchyma. Thyroid and lung are derived from the same endodermal cells, thyroid hormone affect the occurrence、development and prognosis of the chronic obstructive pulmonary disease, lung cancer and other lung diseases, This article reviews the role and mechanism of thyroid hormone in pulmonary fibrosis in order to provide new idea for the study of the role and mechanism of thyroid hormone in silicosis.

Neumonía lipoidea exógena no fibrosante: a propósito de un caso / Non-Fibrosing Exogenous Lipoid Pneumonia: presentation of a case

La neumonía lipoidea exógena (NLE) es una patología inusual, que tiene una incidencia del 1% al 2,5%, y tiene su causa en la aspiración y la acumulación de lípidos de origen exógeno dentro de los alvéolos pulmonares. Cuando el agente aspirado es de composición oleosa, se desencadena una reacción inflamatoria pulmonar denominada neumonía lipoidea, que con el tiempo puede conducir a una fibrosis parenquimatosa irreversible. En ocasiones, se puede presentar en forma de lesiones nodulares, que obligan a un amplio diagnóstico diferencial, en el que desempeñan un papel fundamental los estudios por imágenes. Para el diagnóstico definitivo, se requiere confirmación histopatológica1. Presentamos un caso clínico de neumonía lipoidea que se presentó como masa pulmonar acompañada de infiltrados pulmonares bilaterales.

Exogenous lipoid pneumonia (ELP) is an unusual disease, with an incidence of 1 to 2.5%, caused by aspiration and accumulation of exogenous lipids in the pulmonary alveoli. When the aspirated agent has an oily composition, a pulmonary inflammatory reaction called lipoid pneumonia is triggered, which over time can lead to irreversible parenchymal fibrosis. Sometimes it can appear as nodular lesions that require a broad differential diagnosis, in which case imaging studies have a fundamental role. Histo pathological confirmation is required for definitive diagnosis1. We present a clinical case of lipoid pneumonia which appeared as a lung mass ac companied by bilateral pulmonary infiltrates.

Hallazgos en imágenes de tórax en una intoxicación aguda con paraquat: reporte de un caso / Findings on thorax images in acute paraquat poisoning: case report

Resumen El Paraquat es un herbicida ampliamente utilizado para el control de las malezas en Chile. Su ingesta determina una alta probabilidad de mortalidad dado su inherente toxicidad mediante la producción de radicales libres, que afectan a múltiples órganos, principalmente los pulmones; a esto se suma la falta de un tratamiento efectivo. Se presenta el caso clínico de un hombre de 18 años que en un intento suicida consume 50 mL de paraquat (200 g/L), con desenlace fatal. La presentación clínica depende la cantidad de Paraquat ingerida y los hallazgos radiológicos descritos varían según la temporalidad del cuadro e, inclusive, podrían determinar el pronóstico.

Paraquat is an herbicide widely used for weed control in Chile. Its intake determines a high probability of mortality because of its inherent toxicity through the production of free radicals. Multiple organs are affected, mainly the lungs; to this is added the lack of effective treatment. We present the clinical case of an 18-year-old man who in a suicidal attempt swallows 50 mL of paraquat (200 g/L), with a fatal outcome. The clinical presentation depends on the amount of Paraquat ingested. Radiological findings described vary according to the temporality of the condition and could even determine the prognosis

Acometimento da função ventricular direita em pacientes com esclerose sistêmica e doença pulmonar intersticial: avaliação pelo doppler tecidual / Impairment of right ventricular function in patients with systemic sclerosis and interstitial lung disease: tissue doppler evaluation

Introdução: A esclerose sistêmica (ES) é uma doença autoimune do tecido conjuntivo que cursa com fibrose e disfunção microvascular. O envolvimento dos órgãos viscerais, incluindo os pulmões e o coração, é a principal causa de óbito na ES. Nesse contexto, analisamos a relação entre os parâmetros ventriculares direitos (VD) pela ecocardiografia com Doppler tecidual e o acometimento pulmonar em pacientes com ES. Métodos: Os pacientes que preencheram os Critérios de Classificação da ES de 2013 foram submetidos à ecocardiografia com Doppler tecidual para avaliação da função sistólica (fração de ejeção) ventricular esquerda (VE), enquanto a função sistólica do VD foi avaliada por meio da fração de variação de área do VD (fractional area change ­ FAC), velocidade (sistólica) do Doppler tecidual, índice de desempenho miocárdico (IDM) e excursão sistólica do plano anular tricúspide (TAPSE). A pressão sistólica pulmonar foi estimada por insuficiência tricúspide. A tomografia computadorizada de alta resolução (TCAR) de tórax avaliou a presença de fibrose pulmonar. De acordo com os resultados da TCAR, os pacientes foram divididos em 2 subgrupos: Grupo I, incluindo pacientes com fibrose pulmonar (n=26), e Grupo II sem fibrose (n=17). Resultados: Entre os 43 pacientes com ES, a maioria era do sexo feminino (86%) com idade de 51±12 anos. Todos os pacientes apresentavam função ventricular sistólica normal, avaliada pela FEVE>55% e FAC VD>35%. Não houve diferença significativa em termos de idade ou duração da doença para os grupos. Exceto pela diminuição das velocidades do Doppler tecidual em pacientes com fibrose pulmonar, todos os índices de desempenho do VD foram semelhantes. Conclusão: Em pacientes com ES e fibrose pulmonar, o Doppler tecidual identifica acometimento miocárdico longitudinal precoce do VD, apesar do desempenho sistólico radial preservado do VD.(AU)

Introduction: Systemic sclerosis (SSc) is an autoimmune tissue connective disease that courses with fibrosis and microvascular dysfunction. Involvement of the visceral organs, including the lungs and heart, is the main cause of death among patients with SSc. In this context, here we analyzed the relationship between right ventricle (RV) parameters assessed by tissue Doppler echocardiography and lung involvement in patients with SSc. Methods: Patients fulfilling the 2013 SSc Classification Criteria underwent tissue Doppler echocardiography for the assessment of left ventricular (LV) systolic function (ejection fraction) and RV fractional area change (FAC), tissue Doppler s' (systolic) velocity, myocardial performance index, and tricuspid annular plane systolic excursion for the assessment of RV systolic function. Pulmonary systolic pressure was estimated using tricuspid regurgitation. Chest high-resolution computed tomography was used to evaluate the presence of pulmonary fibrosis. The patients were divided into two subgroups accordingly: Group I, patients with pulmonary fibrosis (n=26); and Group II, those without fibrosis (n=17). Results: Among the 43 patients with SSc, most were female (86%), and the mean age was 51 ± 12 years. All patients had normal systolic ventricular function as evidenced by an LV ejection fraction > 55% and an RV FAC > 35%. No significant intergroup difference was noted in age or disease duration. Except for a decreased tissue Doppler s' velocity in patients with lung fibrosis, all indexes of RV performance were similar. Conclusion: In patients with SSc and pulmonary fibrosis, tissue Doppler identified early RV longitudinal myocardial involvement despite preserved RV radial systolic performance.(AU)

Effects of non-muscle myosin Ⅱ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury / 中华烧伤杂志

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.

Analysis of incidence characteristics and trend of pneumoconiosis in Ningbo City from 1967 to 2019 / 中华劳动卫生职业病杂志

Objective: To understand the incidence of pneumoconiosis in Ningbo city from 1967 to 2019, and to analyze the distribution characteristics and change trend of pneumoconiosis. Methods: In February 2021, the data of pneumoconiosis patients in Ningbo city from 1967 to 2019 were sorted out. The data from 1967 to 1987 were from historical case files of Zhejiang Center for Disease Control and Prevention, the data from 1988 to 2005 were from the historical case files of Ningbo Center for Disease Control and Prevention, and the data from 2006 to 2019 were from the pneumoconiosis report card in China Disease Prevention and Control Information System; Followed up and supplement relevant information, including basic information, basic information of employers and information related to pneumoconiosis diagnosis, and comprehensively analyze the composition and development trend, population characteristics and industry characteristics of pneumoconiosis. Results: From 1967 to 2019, a total of 1715 cases of pneumoconiosis were reported in Ningbo City, including 1254 cases of stageⅠpneumoconiosis, 258 cases of stageⅡpneumoconiosis, 172 cases of stage Ⅲpneumoconiosis. 1202 cases of silicosis (70.09%) , 296 cases of asbestosis (17.26%) , 40 cases of welder's pneumoconiosis (2.33%) , 32 cases of graphite pneumoconiosis (1.87%) were reported. There were 1296 male cases (75.57%) and 419 female cases (24.43%) were reported. Silicosis (91.15%, 1102/1209) and welder's pneumoconiosis (100.00%, 40/40) were the most common pneumoconiosis in males, while asbestosis (90.24%, 268/297) and graphite pneumoconiosis (87.50%, 28/32) were the most common pneumoconiosis in females. The average age was (49.71±10.90) years old and the average length of service was (10.98±6.96) years. The top three reported pneumoconiosis cases were construction industry (336 cases, 19.59%) , ferrous metal smelting and rolling industry (317 cases, 18.48%) and non-metallic mineral products industry (315 cases, 18.37%) . The top three reported pneumoconiosis cases were 414 cases (24.14%) in Ninghai County, 294 cases (17.14%) in Yuyao City and 272 cases (15.86%) in Yinzhou District. Conclusion: With the development of industries in Ningbo City, government departments should strengthen supervision and management of enterprises involving silica dust and welding fume to curb the high incidence of pneumoconiosis.

Research progress of C-X-C motif chemokine ligand 12 and its receptor signaling axis in the regulation of pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.

Interventional effect of asiaticosdide on rats exposed to silica dust / 中华劳动卫生职业病杂志

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.

Preparation of purified proteins from fresh Pheretima and their inhibitory effect against pulmonary fibrosis in mice / 南方医科大学学报

OBJECTIVE@#To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis.@*METHODS@#The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-β1 alone (model group) or in combination with SB431542 (2 μmol/L) or the purified proteins (13.125 μg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of α-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 days, after which HE and Masson staining was used to observe the pathological changes in the lung tissue of the mice.@*RESULTS@#We successfully obtained purified proteins from fresh Pheretima protein by size exclusion chromatography. Treatment with the purified proteins significantly inhibited TGF-β1-induced proliferation of MRC-5 cells (P < 0.01), reduced the cellular expressions of α-SMA, Vimentin and collagen I (P < 0.001 or P < 0.01), increased the expression of E-cadherin (P < 0.01), and inhibited the expressions of Smad2/3 and P-Smad2/3 (P < 0.001 or P < 0.01). In male C57BL/6 mice models of bleomycin-induced pulmonary fibrosis, treatment with the purified proteins obviously reduced the number of inflammatory cells and fibrotic area in the lungs.@*CONCLUSION@#The purified proteins from fresh Pheretima obtained by size exclusion chromatography can inhibit pulmonary fibrosis in mice by regulating the TGF-β/ Smad pathway.