Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

COVID-19 Myocarditis and Severity Factors： An Adult Cohort Study

BackgroundNotwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individuals health conditions; myocarditis incidence rate and hallmarks. MethodsDemographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors. RESULTSIn total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. InterpretationThree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed on March 15, 2020 using the terms ("COVID-19" OR "novel coronavirus" OR "2019 novel coronavirus" OR "2019-nCoV" OR "pneumonia" OR "coronavirus"), AND "Myocarditis" OR "Cycle threshold (Ct)" OR "Altitude". We found that one article analyzed the risk factors affecting the prognosis of adult patients with COVID-19 in terms of survivorship, without considering Ct values as extrinsic factors. Moreover, there are no reported studies on viral myocarditis caused by COVID-19 and the relationship between the altitude and COVID-19. Added value of this studyWe retrospectively analyzed the clinical data, Ct values, laboratory indicators and imaging findings of 84 adult patients with confirmed COVID-19. Three key-independent risk factors of COVID-19 were identified in our study, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Moreover, altitude should be considered for COVID-19 severity classification, given that oxygen partial pressure and blood oxygen saturation of regional patients vary with altitudes. Implications of all the available evidenceThree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.