HIV infection increases the risk of inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVE: In order to synthesize available results regarding human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD), we conducted a systematic review and meta-analysis to provide quantitative estimates of associated risk. METHODS: A systematic search of four scientific databases, PubMed, the Cochrane Library, EMBASE, and Scopus, was performed. The overall odds ratio (OR) with the corresponding 95% CI was calculated via a random effects model. Sensitivity analyses and tests for publication bias were then performed. RESULTS: Of the 3046 articles retrieved, seven studies with a cumulative sample size greater than 57,000,000 were included in our analysis. A subsequent meta-analysis based on a random effects model (heterogeneity test, I2 = 99.9) revealed an association between HIV infection and IBD: OR = 2.68 (95% CI: 1.17, 6.13). The funnel plot of this meta-analysis was asymmetric (Egger's test: P = 0.01), and significant publication bias was found. Sensitivity analysis of the 3 dimensions revealed that the results of this meta-analysis were relatively stable. CONCLUSIONS: A significant correlation may exist between HIV infection and intestinal disease, and more large-scale studies are needed to draw firm conclusions. It is recommended that HIV patients be screened for intestinal diseases.

Mesenchymal stem cell-based therapy for paraquat-induced lung injury.

Paraquat poisoning results in significant pulmonary damage, but current treatments are only minimally effective in repairing the injured lung tissues. Recent research has highlighted the promise of using stem cell therapy, namely mesenchymal stem cells, as a new method for treating paraquat toxicity. These cells have shown effectiveness in decreasing inflammation, apoptosis, and fibrosis in the mice lungs subjected to paraquat. The therapeutic implications of mesenchymal stem cells are believed to arise from their release of bioactive proteins and their capacity to regulate inflammatory responses. However, additional clinical study is required to validate these therapies' efficacy. This review thoroughly explores the pathophysiology of paraquat poisoning and the properties of mesenchymal stem cells. Additionally, it critically assesses the long-term safety and effectiveness of mesenchymal stem cell therapies, which is crucial for developing more dependable and effective treatment protocols. In summary, although mesenchymal stem cells offer promising prospects for treating lung injuries, more investigations are required to optimize their therapeutic promise and ensure their safe clinical application in the context of paraquat poisoning.

Machine learning models for early prediction of potassium lowering effectiveness and adverse events in patients with hyperkalemia.

The aim of this study was to develop a model for early prediction of adverse events and treatment effectiveness in patients with hyperkalemia. We collected clinical data from patients with hyperkalemia in the First Hospital of Zhejiang University School of Medicine between 2015 and 2021. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze the predictors on the full dataset. We randomly divided the data into a training group and a validation group, and used LASSO to filter variables in the training set. Six machine learning methods were used to develop the models. The best model was selected based on the area under the curve (AUC). Shapley additive exPlanations (SHAP) values were used to explain the best model. A total of 1074 patients with hyperkalemia were finally enrolled. Diastolic blood pressure (DBP), breathing, oxygen saturation (SPO2), Glasgow coma score (GCS), liver disease, oliguria, blood sodium, international standardized ratio (ISR), and initial blood potassium were the predictors of the occurrence of adverse events; peripheral edema, estimated glomerular filtration rate (eGFR), blood sodium, actual base residual, and initial blood potassium were the predictors of therapeutic effect. Extreme gradient boosting (XGBoost) model achieved the best performance (adverse events: AUC = 0.87; therapeutic effect: AUC = 0.75). A model based on clinical characteristics was developed and validated with good performance.

Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series.

BACKGROUND: The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals. However, no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans. This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. METHODS: This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022. The entire course of the incidents was described in detail. Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer. Hematoxylin and eosin staining was performed to assess liver injury, and immunofluorescence was used to evaluate hepatic mitophagy. RESULTS: The 2-amino-5-chloro-N,3-dimethylbenzamide powder (99% purity) entered the human body mainly via the skin and respiratory tract due to poor personal protective measures. The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency, rash, fever, organic damage, and recovery phases in accordance with the clinical evolution. Rash and fever may be the important premonitory symptoms for further organ injuries. The chemical was detected in the blood of all patients and caused multiple organ injuries, predominantly liver injury, including kidney, myocardium, and microcirculation. Three patients recovered smoothly after comprehensive treatments, including artificial liver therapy, continuous renal replacement therapy, glucocorticoids, and other symptomatic and supportive treatments. One patient survived by liver transplantation. The postoperative pathological findings of the removed liver showed acute liver failure, and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes. CONCLUSIONS: This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. The chemical enters the body through the respiratory tract and skin during industrial production. The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury. Liver transplantation may be an effective option for patients with severe liver failure. The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Mid-to-late stage diquat accumulation in the central nervous system: A severe case of oral poisoning.

A 54-year-old woman in good health was admitted to our hospital with diquat poisoning. The patient drank an unknown dose of diquat, and acute kidney injury developed early. However, there were no obvious pulmonary abnormalities and no signs of central nervous system toxicity in the early stage. The woman underwent active treatment, which resulted in a significant decrease in blood diquat levels, but her lung condition progressively worsened and neurological symptoms developed. Fortunately, the patient survived after intensive hemoperfusion combined with continuous renal replacement therapy (CRRT), intracranial pressure reduction, and anti-infective treatment. This case report highlights the importance of being aware of the development of delayed pulmonary symptoms and neurologic complications when caring for patients poisoned with diquat, even in those with low diquat blood concentrations. Interestingly, we also detected the concentration of diquat in the cerebrospinal fluid (CSF) of patients with diquat poisoning, and found that the rate of decrease of diquat concentration in the CSF was considerably slower than that in the blood.Notably, a specific correlation was observed between the concentration of diquat in the CSF, rather than in the blood, and both the intracranial pressure (ICP) and the severity of cerebral edema in this patient.

Assessment of pulmonary fibrosis induced by paraquat using Al18F-NODA-FAPI-04 PET/CT.

The lack of a highly sensitive method to evaluate paraquat (PQ)-induced pulmonary fibrosis and predict disease progression remains an unresolved clinic issue. Fibroblast activation protein (FAP) may play an important role in the pathogenesis of PQ-induced pulmonary fibrosis. We aimed to evaluate the role of FAP in the PQ-induced pulmonary fibrosis and the utility of fibroblast activation protein inhibitor (FAPI) for positron emission tomography (PET) imaging in PQ-induced pulmonary fibrosis. In our study, two cases of PQ poisoning were presented and FAPI PET/CT was performed as a novel imaging technique. The uptake of FAPI increased in both cases of PQ poisoning. Animal experiments were then performed to validate the findings in the patients. Physiological FAPI lung uptake was higher in mice of the PQ group than in the control group. The results of histological analysis and Western blot were consistent with the findings of PET/CT imaging. The pulmonary fibrosis animal model was developed by intragastric gavage of PQ. PET/CT imaging was performed after injection of FAPI. Lung tissues of mice were collected for fibrosis assessment after imaging. Immunohistochemistry for FAP, histology and Western blot for collagen were performed to further validate the imaging findings. In conclusion, FAPI was involved in the pathogenesis of fibrosis induced by PQ, and PET/CT with FAPI could detect lung fibrogenesis, making it a promising tool to assess early disease activity and predict disease progression.

Structural basis of λCII-dependent transcription activation.

The CII protein of bacteriophage λ activates transcription from the phage promoters PRE, PI, and PAQ by binding to two direct repeats that straddle the promoter -35 element. Although genetic, biochemical, and structural studies have elucidated many aspects of λCII-mediated transcription activation, no precise structure of the transcription machinery in the process is available. Here, we report a 3.1-Å cryo-electron microscopy (cryo-EM) structure of an intact λCII-dependent transcription activation complex (TAC-λCII), which comprises λCII, E. coli RNAP-σ70 holoenzyme, and the phage promoter PRE. The structure reveals the interactions between λCII and the direct repeats responsible for promoter specificity and the interactions between λCII and RNAP α subunit C-terminal domain responsible for transcription activation. We also determined a 3.4-Å cryo-EM structure of an RNAP-promoter open complex (RPo-PRE) from the same dataset. Structural comparison between TAC-λCII and RPo-PRE provides new insights into λCII-dependent transcription activation.

Development and validation of a predictive model for the assessment of potassium-lowering treatment among hyperkalemia patients.

BACKGROUND: Hyperkalemia is common among patients in emergency department and is associated with mortality. While, there is a lack of good evaluation and prediction methods for the efficacy of potassium-lowering treatment, making the drug dosage adjustment quite difficult. We aimed to develop a predictive model to provide early forecasting of treating effects for hyperkalemia patients. METHODS: Around 80% of hyperkalemia patients (n=818) were randomly selected as the training dataset and the remaining 20% (n=196) as the validating dataset. According to the serum potassium (K+) levels after the first round of potassium-lowering treatment, patients were classified into the effective and ineffective groups. Multivariate logistic regression analyses were performed to develop a prediction model. The receiver operating characteristic (ROC) curve and calibration curve analysis were used for model validation. RESULTS: In the training dataset, 429 patients had favorable effects after treatment (effective group), and 389 had poor therapeutic outcomes (ineffective group). Patients in the ineffective group had a higher percentage of renal disease (P=0.007), peripheral edema (P<0.001), oliguria (P=0.001), or higher initial serum K+ level (P<0.001). The percentage of insulin usage was higher in the effective group than in the ineffective group (P=0.005). After multivariate logistic regression analysis, we found age, peripheral edema, oliguria, history of kidney transplantation, end-stage renal disease, insulin, and initial serum K+ were all independently associated with favorable treatment effects. CONCLUSION: The predictive model could provide early forecasting of therapeutic outcomes for hyperkalemia patients after drug treatment, which could help clinicians to identify hyperkalemia patients with high risk and adjust the dosage of medication for potassium-lowering.