BackgroundParaquat poisoning is well known for causing multiple organ function failure (MODS) and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning.ObjectiveTo study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat.MethodA total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning); the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day); and a control group (rats were administered intragastric physiological saline). On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1), endothelin-1 (ET-1), and hydroxyproline (HYP) in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes.ResultThe TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered.ConclusionBosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

OBJECTIVE To evaluate the safety and efficacy of leflunomide for the treatment of refractory COVID-19 in adult patients. DESIGN Open-label controlled study SETTING A designated hospital for patients with refractory COVID-19 in Wuhan, China. PARTICIPANTS 27 hospitalized adult patients (≥18 years of age) with radiologically confirmed pneumonia and SARS-CoV-2 positive for more than 28 days despite standard care were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. MAIN OUTCOME MEASURES The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. RESULTS Twelve patients enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide versus 16.7% for grp 1 patients (2/12) (P=0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12; IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (P=0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 versus 8.3% (1/12) for grp 1 (P=0.001). The 30-day discharge rate was 100% (15/15) for the grp 2 versus 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. CONCLUSION Leflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The addition of leflunomide to SOC did not increase adverse events versus SOC. These preliminary observations underscore a need for a randomized clinical study of leflunomide in SARS-CoV-2 infection.

Nitrobenzene poisoning is uncommon, with most cases occurring in the dye, paint, and other chemical industries. Nitrobenzene enters the body mainly through the skin, respiratory tract, and oral cavity. Nitrobenzene poisoning symptoms include hypermethemoglobinemia, hemolytic anemia, liver and kidney dysfunction, cardiogenic pulmonary edema, and toxic encephalopathy, which endanger people’s lives. Therefore, we present a case of nitrobenzene poisoning caused by skin absorption, focusing on its clinical characteristics and treatment outcomes. A 58 years-old man presented to our department with confusion and cyanosis. He has a history of hypertension and cerebral infarction. The patient was diagnosed with moderate occupational acute benzene poisoning with nitro compounds. Symptomatic support, methylene blue, and other antioxidant treatments were commenced after diagnosis. After treatment, the patient’s condition gradually improved, and he was discharged.

In the present study, the successful management of severe paraquat (PQ) poisoning with multiple organ dysfunction syndrome is described. A 42-year-old female ingested >100 ml PQ (20% weight/volume) in an attempted suicide. After 22 h the patient was admitted to hospital with serious liver, kidney and lung damage. Comprehensive therapy that maximized poison elimination was administered, along with appropriate glucocorticoids and medication for anticoagulation and protection of the liver and kidney. The patient was successfully treated and recovered after 40 days. However, pulmonary damage was aggravated when the glucocorticoid treatment was stopped after 2 months; the lungs recovered again following systematic therapy. Subsequent to a 8-month follow-up, the patient was able to look after herself in her daily life. To the best of our knowledge, successful treatment following severe PQ poisoning is rare.

The present report describes two cases of paraquat poisoning by skin absorption. The cases involved contractual workers who were spraying paraquat in an orchard. Whilst spraying, some solution adhered to their skin. The skin developed erythema followed by blistering and hemorrhaging hemorrhagic diabrosis. Six days later the patients were admitted to the Department of Poisoning and Occupational Disease, Qilu Hospital of Shandong University (Jinan, China) with 3 and 2% total body surface area (TBSA) burns, respectively. Surgical debridement was performed and immunosuppressants were administered during the patients’ treatment. The patients were treated successfully and had made a complete recovery following 21 days. From these cases it was examined how paraquat may cause skin injuries and occasionally poisoning. To the best of our knowledge, cases of paraquat poisoning are rare in China. A review of the relevant literature was performed.

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Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care.Methods: In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate.Results: 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide vs. 16.7% for grp 1 patients (2/12) (p = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1–12, IQR 1–12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (p = 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 (p = 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported.Conclusion: Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14–28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.

Keratin is the main component of cellular intermediate filaments, and its post-translational modification plays an important role in cell differentiation and apoptosis, as well as disease states. The conversion of peptidylarginine to citrulline, termed citrullination, is particularly involved in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemistry using an antibody mixture that broadly recognized various keratin forms detected cytokeratin in many cells in the area lining the synovial membrane of RA. Furthermore, double immuno-florescent labeling showed that the cells expressing cytokeratin were also positive for citrulline when they were in the vicinity of extracellular deposits or approached the exterior of the synovial membrane. Western blot analysis demonstrated citrullination of keratin purified from RA synovial tissue by immuno-precipitation. The above results indicate the presence of citrullinated cytokeratin in synovial membranes in RA.