Tim-3 facilitates immune escape in benzene-induced acute myeloid leukemia mouse model by promoting macrophage M2 polarization.

Benzene poisoning can cause acute myeloid leukemia (AML) through a variety of passways. Tim-3 has gained prominence as a potential candidate in mediating immunosuppression in tumor microenvironments. The macrophage polarization is also related to immune escape. Herein, we reported that Tim-3 and macrophage M2 polarization play a vital role in benzene-induced AML. First, the benzene-induced AML C3H/He mouse model was constructed by subcutaneously injecting 250 mg/kg of benzene. After six months, macrophage phenotype, cytokines, and Tim-3 expression levels were investigated. Flow cytometry assay revealed that the T-cell inhibitory receptor Tim-3 was significantly upregulated in both bone marrow and spleen of the benzene-induced AML mouse model. Elisa's results displayed a decreased serum level of IL-12 while increased TGF-ß1. Mechanistically, changes in cytokine secretion promote the growth of M2-type macrophages in the bone marrow and spleen, as determined by immunofluorescence assay. The increased levels of PI3K, AKT, and mTOR in the benzene-exposure group further proved the crucial role of Tim-3 in regulating the functional status of macrophages in the AML microenvironment. These results demonstrate that Tim-3 and macrophage polarization may play a vital role during the immune escape of the benzene-induced AML. This study provides a new potential intervention site for immune checkpoint-based AML therapeutic strategy.

Study on the therapeutic effect of glucocorticoids on acute kidney injury in rats exposed to diquat.

AIMS: To preliminarily explore, whether glucocorticoids have a therapeutic effect on diquat-induced acute kidney injury in rats. METHOD: 150 Wistar rats were randomly divided into six groups: exposure model group (DQ group), dexamethasone control group (GC group), blank control group (Ctrl group), dexamethasone 2.1 mg/kg dose group (DQ+L-GC group), dexamethasone 4.2 mg/kg dose group (DQ+M-GC group), and dexamethasone 8.4 mg/kg dose group (DQ+H-GC group), with 25 rats in each group. Each group was further divided into five subgroups, 24 h, 3 d, 7 d, 14 d, and 21 d after exposure, according to the feeding time and the course of treatment, with five animals in each subgroup. The rats in DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups were administered 115.5 mg/kg diquat by gavage, respectively. Moreover, 30 min after gavage, rats in DQ+L-GC group, DQ+M-GC group, DQ+H-GC group and GC group were intragastric administered dexamethasone 2.1 mg/kg, 4.2 mg/kg, 8.4 mg/kg and 8.4 mg/kg, respectively. After 7 days, the intraperitoneal injection of dexamethasone was changed to 6.3 mg/kg prednisone by intragastric administration. Subsequently, 7 days later, it was changed to 3.15 mg/kg prednisone by intragastric administration until the end of the experiment on 21 days. After the start of the experiment, changes in the conditions of the rats in each group were observed at a fixed time every day, changes in the body weight of the rats were monitored at the same time, and the death of the rats was recorded at 24 h, 3 d, 7 d, 14 d, and 21 d after exposure. The rats were sacrificed by an intraperitoneal injection of 100 mg/kg sodium pentobarbital overdose. Blood was collected by puncture of the inferior vena cava, used to determine Cr and BUN. The upper segment of the left kidney was collected for histopathological examination. Elisa was used to detect neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the lower segment of left kidney. TLR4, Myd88, and NF-κB were detected in the right kidney. RESULTS: (1) After exposure, most rats in DQ group, DQ+L-GC group, DQ+M-GC group and DQ+H-GC group showed shortness of breath, oliguria, diarrhea, yellow hair and other symptoms. No symptoms and related signs were observed in Ctrl group and GC group. (2) The weight of rats in the Ctrl group and the GC group increased slowly during the test. the body weight of the rats in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups continued to decrease after self-infection. Body weight dropped to the lowest point at approximately 7 d, and gradually increased from 7 d to 21 d. (3) A small amount of capillary congestion in the medulla was observed after 7 days in the GC group. The DQ group showed tubular atrophy, edema of the epithelial cells, and over time, the tubules were seen dilated and became irregular in shape; large amount of capillary congestion was also observed in the renal cortex and medulla. The renal injury in the DQ+L-GC group was less than that in the DQ group. DQ+H-GC group had no obvious injury before 7 d, but more renal tubules were seen in the DQ+H-GC group from 7 d to 14 d. (4) Compared with the DQ group, there was no difference before 14 d, and at 14 d-21 d, DQ+L-GC group, DQ+M-GC group, DQ+H-GC group all had different degrees of decline. NGAL content: Compared with the DQ group, the content of NGAL and KIM-1 in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups decreased compared with the DQ group at each time node. (5) Compared with the Ctrl group, the expression of TNF-α, TLR4, MyD88, NF-κB in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node increased in the renal tissue. The content of TNF-α, TLR4, MyD88, NF-κB in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node was lower than that in the DQ group. CONCLUSION: (1) Diquat can cause kidney damage in rats, mainly manifested as renal tubular atrophy, epithelial cell edema, capillary congestion and dilation, and the renal function damage indicators have been improved to varying degrees. (2) Glucocorticoids have therapeutic effects on acute kidney injury in rats exposed to diquat. During the treatment, the efficacy of glucocorticoids did not increase with increasing doses after reaching a dose of 4.2 mg/kg. (3) TLR4 receptor-mediated TLR4/Myd88/NF-κB signaling pathway is involved in the inflammatory response of acute kidney injury in diquat poisoning rats. Glucocorticoids can inhibit the inflammatory response, thereby affecting the expression of TLR4/Myd88/NF-κB signaling pathway-related proteins.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report.

BACKGROUND: Xanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing. CASE PRESENTATION: We reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient's multiple organ failure gradually worsened, ultimately leading to death. CONCLUSION: Xanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

Current situation and influencing factors for suicidal intent in patients with intentional acute pesticide poisoning.

Introduction: Since pesticides have been widely used in agricultural production, acute pesticide poisoning (APP) has gradually become a worldwide public health problem. Recently, the number of APP cases has been high in China, and the intentional self-administration of pesticides is the main cause of APP. However, there is a lack of relevant studies on the factors influencing suicidal intent in patients with intentional APP. This study aimed to explore the current situation and influencing factors for suicidal intent among patients with intentional APP. Methods: In this cross-sectional study, we enrolled a total of 225 patients with intentional APP admitted to the emergency department of our Grade A comprehensive hospital in Shandong Province between June 2019 and January 2021. Patients were investigated using a health status interview questionnaire, Beck Suicidal Intent Scale, Duke Social Support Index, psychological stress scale, Dickman Impulsivity Inventory, Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale, and Beck Hopelessness Scale. Descriptive statistics, single-factor analysis, and multiple linear regression were used for data analysis. Results: Suicidal intent scores were collected and averaged (14.23 ± 6.22). Multiple linear regression analysis revealed that marital status, residential area, impulsivity, hopelessness, depression, psychological strain, and social support impact suicidal intent. Conclusion: Patients with intentional APP have high suicidal intent. Therefore, different interventions should be tailored to different patients.

Case Report: Acute Intoxication from Phosphine Inhalation.

Aluminum phosphide is a highly effective insecticide for fumigation in granaries and is often used in rural grain storage. However, people's awareness of its toxicity is not strong. A case of acute inhalation toxicity of phosphine caused by the use of aluminum phosphide to fumigate a granary is reported here. The case presented with aspiration pneumonia and acute left heart failure. The patient was cured using comprehensive life support treatment, including respiratory support, antiarrhythmic treatment, and blood pressure maintenance with vasoactive drugs. There is no specific antidote for phosphine poisoning at present, and the comprehensive application of restricted fluid resuscitation, high-dose glucocorticoid shock, vasoactive drugs and bedside hemofiltration is significant in improving the prognosis of patients. It is also important to remind people to pay attention to their own protection in the process of using aluminum phosphide.

Case report: Methemoglobinemia caused by nitrobenzene poisoning.

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.

Toxic Encephalopathy and Methemoglobinemia after 5-Amino-2-(trifluoromethyl)pyridine Poisoning.

The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.

Case series: Diquat poisoning with acute kidney failure, myocardial damage, and rhabdomyolysis.

Diquat is a herbicide that can have deleterious effects on the kidneys, liver, heart, lungs, and central nervous system on ingestion. Diquat poisoning-associated rhabdomyolysis has rarely been reported. We describe two cases of diquat poisoning with acute renal failure, myocardial damage, and rhabdomyolysis. Case 1: A 17-year-old man experienced anuria after ingesting ~200 mL of diquat 16 h prior. On admission, his creatinine (400 µmol/L), urea (11.7 mmol/L), creatine kinase (2,534 IU/L), and myohemoglobin (4,425 ng/mL) concentrations were elevated. Case 2: An 18-year-old woman who ingested ~200 mL of diquat 5.5 h prior to admission had normal creatinine, urea, and creatine kinase concentrations. Eleven hours after ingestion, she developed anuria with elevated creatinine (169 µmol/L) concentration; her creatine kinase (13,617 IU/L) and myohemoglobin (>3,811 ng/mL) concentrations were remarkably elevated 24 h after ingestion. Both patients also had elevated aminotransferase and myocardial enzyme concentrations. After undergoing hemoperfusion and hemofiltration, blood diquat concentrations in cases 1 and 2 on admission (16/6 h after ingestion), after hemoperfusion (20/11 h after ingestion), and after 8 h of hemofiltration/8 h of hemofiltration and 2 h of hemoperfusion (29/21 h after ingestion) were 4.9/9.1, 3.4/5.4, and 1.5/1.2 µg/mL, respectively. Severe diquat poisoning can cause acute kidney failure and rhabdomyolysis. Rhabdomyolysis may induce myocardial injury, aggravating kidney damage, and also increase transaminase concentration. Hemoperfusion and hemofiltration could be effective treatments for eliminating diquat in the blood.

Severe methyl bromide poisoning causing early acute renal failure and anuria: a case report.

Methyl bromide is a pre-plant soil fumigant that is widely used to control nematodes, insects, and fungi in farmlands. Methyl bromide enters the human body through dermal absorption or inhalation and can damage the respiratory, nervous, circulatory, urinary, and other systems. A 62-year-old man who had inhaled a large amount of methyl bromide was admitted to our department. He presented with respiratory failure and pink foamy sputum. He was started on dexamethasone, alanyl glutamine, sulbactam, furosemide, vitamin B1, mouse nerve growth factor, and other treatments, and mechanical ventilation and continuous venovenous hemodiafiltration (CVVHF) were performed daily. He subsequently developed coagulopathy because of the CVVHF, for which protamine, recombinant human brain natriuretic peptide, and albumin were administered intravenously. Notably, the patient developed sustained anuria and eventually died owing to multiple organ failure; specifically, failure of the brain, heart, lungs, and kidneys. This report presents the diagnosis, clinical course, management, and prognosis of a patient who was treated at our hospital for severe methyl bromide poisoning.

Clinical analysis of pipeline dredging agent poisoning: A case report.

BACKGROUND: Pipeline dredging agents are new household deep cleaning products used to dredge blockages in kitchen and bathroom pipeline caused by grease, hair, vegetable residue, paper cotton fibre, and other organic substances. Pipeline dredging agents are corrosive chemicals that can cause poisoning through corrosive damage to the digestive tract; however, this has not been reported clinically. Therefore, this report emphasises that oral pipeline dredging agent poisoning can cause corrosive damage to the digestive tract and may have serious health consequences. CASE SUMMARY: A 68-year-old man consumed liquor (200 mL) at approximately 13:00 on April 22, 2021. At approximately 16:00, his family found him unresponsive with blackened lips, blood spots in the corners of the mouth, and blood stains on the ground, as well as an empty bottle of a pipeline dredging agent. One hour later, he was admitted to the emergency department of a local hospital. Considering the empty bottle, he was suspected to have sustained severe corrosive damage to the digestive tract and was transferred to our department at 23:15 on April 22, 2021. He developed dysphagia and intermittent fever and experienced difficulty in opening his mouth throughout his hospital stay. The patient's condition gradually stabilised. However, he suddenly developed respiratory failure on day 12, and endotracheal intubation and ventilator-assisted ventilation were performed. However, the patient died after 1.5 h despite emergency rescue efforts. CONCLUSION: Pipeline dredging agents are highly corrosive and may cause corrosive damage to the digestive tract and asphyxia upon consumption.

The toxicokinetics of acute paraquat poisoning in specific patients: a case series.

Paraquat is a non-selective contact herbicide that is absorbed through the digestive tract and skin and can cause multiple organ damage. The toxicokinetics of paraquat poisoning in specific patients are rarely reported. Case 1 was a 76-year-old man who intermittently immersed his perineum in diluted paraquat solution for 3 consecutive days because of eczema of the perineal skin. On admission, the patient's scrotal skin was severely corroded and his blood paraquat concentration was 0.5 µg/mL. He developed severe kidney and lung damage after admission and died on Day 6 of admission. Case 2 was a 23-year-old woman who ingested paraquat during gestational week 36. Her initial blood paraquat concentration was 0.81 µg/mL. The patient refused hemoperfusion and a cesarean section. She birthed a baby girl 83 hours after ingesting paraquat. Paraquat concentrations in postnatal maternal blood, fetal blood, umbilical cord blood, and amniotic fluid were 0.19 µg/mL, 0.23 µg/mL, 0.20 µg/mL, and 0.47 µg/mL, respectively. The baby died within hours of birth and the mother died of refractory respiratory failure 2 days after delivery. This paper provides clues about paraquat toxicokinetics in specific patient types and indicates that paraquat can be absorbed through the scrotal skin and the placental barrier.

Methemoglobinemia and Delayed Encephalopathy After 5-Bromo-2-Nitropyridine Poisoning: A Rare Case Report.

5-bromo-2-nitropyridine, an intermediate in the synthesis of pharmaceutical and pesticide products, is toxic to the human body. However, 5-bromo-2-nitropyridine poisoning has not been previously reported. Here, we report the case of a 40-year-old man who suffered skin and respiratory tract exposure to leaked 5-Bromo-2-nitropyridine at work. After exposure, the patient rapidly developed dizziness, fatigue, nausea, vomiting, chest distress, diffuse cyanosis, and coma. Methemoglobinemia, hemolytic anemia, rhabdomyolysis, and acute renal failure were observed after admission. He improved markedly after treatment, but delayed encephalopathy was confirmed 82 days after the exposure. This case highlights that 5-bromo-2-nitropyridine can be absorbed through the skin and respiratory tract, resulting in methemoglobinemia and delayed encephalopathy.

Clinical Analysis of Acute Organophosphorus Pesticide Poisoning and Successful Cardiopulmonary Resuscitation: A Case Series.

Acute organophosphorus pesticide poisoning (AOPP) with cardiac arrest has an extremely high mortality rate, and corresponding therapeutic strategies have rarely been reported. Therefore, this study aimed to explore the prognostic factors and effective treatments of AOPP-related cardiac arrest. This retrospective study was conducted in our department in the years 2018-2021. We conducted a descriptive analysis of the clinical manifestations, rescue strategies, and prognosis of patients with AOPP who had experienced cardiac arrest and successful cardiopulmonary resuscitation. This study included six cases of patients with AOPP in addition to cardiac arrest; in four cases, cardiac arrest occurred <12 h after ingestion, and in two, cardiac arrest occurred more than 48 h after ingestion. Five patients had not undergone hemoperfusion therapy before cardiac arrest, and all six were treated with atropine during cardiopulmonary resuscitation and subsequent pralidoxine. Four patients recovered and were discharged from the hospital, one died in our department, and one was transferred to a local hospital and died there 2 h later. The last two patients had severe pancreatic injuries and disseminated intravascular coagulation. This, along with their death, might have been related to their prognosis. Cardiac arrest can occur in patients with severe AOPP for whom antidote administration was insufficient or not timely. Application of atropine and pralidoxine in a timely manner after cardiac arrest following AOPP is the key to successful treatment. This study provides useful guidelines for the treatment of similar cases in the future.

Development and validation of a prediction model of deep venous thrombosis for patients with acute poisoning following hemoperfusion: a retrospective analysis.

OBJECTIVE: To develop and confirm an individualized predictive model to ascertain the probability of deep venous thrombosis in patients with acute poisoning after undergoing hemoperfusion. METHODS: Three hundred eleven patients with acute poisoning who were admitted to a hospital in China between October 2017 and February 2019 were included in the development group. Eighty patients with acute poisoning who were admitted between February and May 2019 were included in the validation group. The independent risk factors for deep venous thrombosis were examined. An individualized predictive model was developed using regression coefficients. RESULTS: The number of catheter indwelling days, having a catheter while being transported, elevated serum homocysteine concentrations, and dyslipidemia were independent risk factors for deep venous thrombosis following hemoperfusion in patients with acute poisoning. The areas under the receiver operating characteristic curve of the development and validation groups were 0.713 and 0.702, respectively, which suggested that the prediction model had good discrimination capacity. The calibration belts of the two groups were ideal. CONCLUSIONS: Our prediction model has a moderate predictive effect for the occurrence of deep venous thrombosis in patients with acute poisoning. In clinical practice, this model could be combined with a common thrombosis risk assessment model.

A rare form of intoxication: acute methyl ethyl ketone peroxide poisoning.

We report two suicidal cases of acute methyl ethyl ketone peroxide (MEKP) poisoning. A woman in her late 60s suffered from oral mucosal erosion, functional impairment of the heart, liver and other organs, pulmonary inflammation, elevated inflammatory markers, pleural effusion, hypoproteinemia and metabolic acidosis after oral administration of approximately 50 mL of MEKP. After admission, the patient was administered hemoperfusion four times, 8 mg of betamethasone for 6 days and symptomatic support. Hemoperfusion had an obvious effect on the treatment of oral MEKP poisoning. After discharge, the patient developed progressive dysphagia and secondary esophageal stenosis. Supplementary feeding was administered with a gastrostomy tube after the patient was completely unable to eat. A man in his mid-40s developed oropharyngeal mucosal erosion, bronchitis and esophageal wall thickening after oral administration of 40 ml MEKP. After receiving total gastrointestinal dispersal, 80 mg of methylprednisolone was administered for 7 days, and symptomatic supportive treatment was provided. Slight dysphagia was observed after discharge, and there was no major effect on the quality of life. Patients with acute oral MEKP poisoning should be followed up regularly to observe its long-term effects on digestive tract corrosion and stenosis.

Acute diquat poisoning resulting in toxic encephalopathy: a report of three cases.

INTRODUCTION: Diquat-related acute kidney injury is well-known. However, neurological disorders caused by diquat are often underestimated, and changes in the imaging findings are rarely reported. We present three cases of acute diquat poisoning resulting in toxic encephalopathy. CASE REPORT: In the first case, a 20-year-old previously healthy man ingested approximately 80-100 mL of diquat. He developed acute renal failure, neurological disorders, and respiratory failure. Central pontine myelinolysis was considered by magnetic resonance imaging (MRI), 18 days after ingestion. In the second case, a 20-year-old man ingested approximately 100 mL of diquat. Toxic encephalopathy was confirmed by MRI, 13 days after ingestion. Unfortunately, he experienced cardiac arrest and died 18 days after ingestion. In the third case, a 31-year-old previously healthy man ingested approximately 50 mL of diquat. The imaging features of toxic encephalopathy mainly involved the medulla oblongata, pons, midbrain, bilateral brachium pontis, cerebellum, and pedunculus cerebri. He demonstrated significant recovery. DISCUSSION: Ingestion of diquat can cause acute renal failure, neurological disorders, and respiratory failure. The pons, midbrain, pedunculus cerebri may be the most commonly impaired locations of diquat-related toxic encephalopathy.

Gluteal muscle damage and rhabdomyolysis after olanzapine poisoning: a case report.

Olanzapine is a widely adopted atypical antipsychotic medication used to manage schizophrenia. Reports show that the incidence rate of adverse reactions to olanzapine is significantly lower than those of other classic antipsychotic medications. However, olanzapine overdose may be associated with severe consequences. Herein, we report a 21-year-old female patient who had taken nearly 700 mg (70 tablets) of olanzapine; she was found after 30 hours. As her condition progressed, she presented with rhabdomyolysis, swelling in the thighs and hips, paralytic ileus, digestive tract hemorrhage, and elevated serum amylase and lipase levels; notably, she recovered after treatment. This intractable case is of great clinical significance and suggests that early-phase hemoperfusion plays a critical role in olanzapine poisoning-related rhabdomyolysis.