Incubation period, clinical and lung CT features for early prediction of COVID-19 deterioration: development and internal verification of a risk model.

BACKGROUND: Most severe, critical, or mortal COVID-19 cases often had a relatively stable period before their status worsened. We developed a deterioration risk model of COVID-19 (DRM-COVID-19) to predict exacerbation risk and optimize disease management on admission. METHOD: We conducted a multicenter retrospective cohort study with 239 confirmed symptomatic COVID-19 patients. A combination of the least absolute shrinkage and selection operator (LASSO), change-in-estimate (CIE) screened out independent risk factors for the multivariate logistic regression model (DRM-COVID-19) from 44 variables, including epidemiological, demographic, clinical, and lung CT features. The compound study endpoint was progression to severe, critical, or mortal status. Additionally, the model's performance was evaluated for discrimination, accuracy, calibration, and clinical utility, through internal validation using bootstrap resampling (1000 times). We used a nomogram and a network platform for model visualization. RESULTS: In the cohort study, 62 cases reached the compound endpoint, including 42 severe, 18 critical, and two mortal cases. DRM-COVID-19 included six factors: dyspnea [odds ratio (OR) 4.89;confidence interval (95% CI) 1.53-15.80], incubation period (OR 0.83; 95% CI 0.68-0.99), number of comorbidities (OR 1.76; 95% CI 1.03-3.05), D-dimer (OR 7.05; 95% CI, 1.35-45.7), C-reactive protein (OR 1.06; 95% CI 1.02-1.1), and semi-quantitative CT score (OR 1.50; 95% CI 1.27-1.82). The model showed good fitting (Hosmer-Lemeshow goodness, X2(8) = 7.0194, P = 0.53), high discrimination (the area under the receiver operating characteristic curve, AUROC, 0.971; 95% CI, 0.949-0.992), precision (Brier score = 0.051) as well as excellent calibration and clinical benefits. The precision-recall (PR) curve showed excellent classification performance of the model (AUCPR = 0.934). We prepared a nomogram and a freely available online prediction platform ( https://deterioration-risk-model-of-covid-19.shinyapps.io/DRMapp/ ). CONCLUSION: We developed a predictive model, which includes the including incubation period along with clinical and lung CT features. The model presented satisfactory prediction and discrimination performance for COVID-19 patients who might progress from mild or moderate to severe or critical on admission, improving the clinical prognosis and optimizing the medical resources.

Polyethylenimine-stabilized silver nanoclusters act as an oxidoreductase mimic for colorimetric determination of chromium(VI).

A new and efficient assay is proposed for the photometric determination of Cr6+ by employing polyethylenimine-stabilized Ag nanoclusters (PEI-AgNCs) as an oxidoreductase mimic. Cr6+ with certain oxidicability is able to specifically react with 3,3',5,5'-tetramethylbenzidine (TMB), giving a color change from colorless to blue indicating the presence of Cr6+. However, the redox kinetics is so slow that the sensitivity obtained for Cr6+ determination is very poor. It is interestingly found that PEI-AgNCs can act as an oxidoreductase-like nanozyme to significantly promote the sluggish reaction, making it possible to rapidly detect toxic Cr6+ with remarkably enhanced performance. With the use of PEI-AgNCs, fast and convenient determination of Cr6+ was realized, with a limit of detection as low as 1.1 µM. Additionally, the proposed assay exhibited excellent selectivity; other ions, including Cr3+, hardly affected the determination of Cr6+. Graphical abstract Polyethylenimine-stabilized silver nanoclusters (PEI-AgNCs) act as an oxidoreductase mimic to catalyze the redox reaction of Cr6+ and 3,3',5,5'-tetramethylbenzidine (TMB), enabling the high-performance colorimetric determination of toxic Cr6+.

[Advances in studies on chemical constituents, pharmacological effects and clinical application of Aspongopus chinensis].

The Aspongopus chinensis is an insect of the genus Hemiptera, which can be used both as a medicinal and as a gourmet in the folk. It has a long history as a drug, which has the effect of regulating Qi and relieving pain, and warming the Yang. It is mainly used to treat stomach cold and pain, liver and stomach pain, kidney deficiency and impotence, and waist and knee pain. Modern pharmacological studies have shown that A. chinensis has a variety of pharmacological activities. For example, it can be used to fight tumors, improve reproductive damage, and antibacterial, anti-oxidation, anti-coagulation, anti-ulcer, anti-fatigue and so on. The chemical constituents of A. chinensis currently reported mainly include odorous components, vitamins, fatty acids and proteins, amino acids, and other nutrients, as well as nucleosides and dopamines. This study summarizes and analyzes the related research literatures of A. chinensis in China and abroad, and provides a reference for its further development and research from the aspects of chemical composition, pharmacological action and clinical application.

Explainable ensemble machine learning model for prediction of 28-day mortality risk in patients with sepsis-associated acute kidney injury.

Background: Sepsis-associated acute kidney injury (S-AKI) is a major contributor to mortality in intensive care units (ICU). Early prediction of mortality risk is crucial to enhance prognosis and optimize clinical decisions. This study aims to develop a 28-day mortality risk prediction model for S-AKI utilizing an explainable ensemble machine learning (ML) algorithm. Methods: This study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.0) database to gather information on patients with S-AKI. Univariate regression, correlation analysis and Boruta were combined for feature selection. To construct the four ML models, hyperparameters were tuned via random search and five-fold cross-validation. To evaluate the performance of all models, ROC, K-S, and LIFT curves were used. The discrimination of ML models and traditional scoring systems was compared using area under the receiver operating characteristic curve (AUC). Additionally, the SHapley Additive exPlanation (SHAP) was utilized to interpret the ML model and identify essential variables. To investigate the relationship between the top nine continuous variables and the risk of 28-day mortality. COX regression-restricted cubic splines were utilized while controlling for age and comorbidities. Results: The study analyzed data from 9,158 patients with S-AKI, dividing them into a 28-day mortality group of 1,940 and a survival group of 7,578. The results showed that XGBoost was the best performing model of the four ML models with AUC of 0.873. All models outperformed APS-III 0.713 and SAPS-II 0.681. The K-S and LIFT curves indicated XGBoost as the most effective predictor for 28-day mortality risk. The model's performance was evaluated using ROCpr curves, calibration curves, accuracy, precision, and F1 scores. SHAP force plots were utilized to interpret and visualize the personalized predictive power of the 28-day mortality risk model. Additionally, COX regression restricted cubic splines revealed an interesting non-linear relationship between the top nine variables and 28-day mortality. Conclusion: The use of ensemble ML models has shown to be more effective than the LR model and conventional scoring systems in predicting 28-day mortality risk in S-AKI patients. By visualizing the XGBoost model with the best predictive performance, clinicians are able to identify high-risk patients early on and improve prognosis.

Comparative proteomic analysis of cellular response of human airway epithelial cells (A549) to benzo(a)pyrene.

This work aimed to investigate the cellular response of human airway epithelial cells (A549) to oxidative stress induced by benzo(a)pyrene [B(a)P]. Levels of intracellular reactive oxygen species (ROS) and lipid peroxidation were investigated in A549 cells treated with varying concentrations of B(a)P. A comparative proteomic analysis of total proteins was performed in cells treated with 1 µM B(a)P [B(a)P-1] and untreated cells. The expression of Mn superoxide dismutase (Mn SOD), one of the identified down-regulated proteins in B(a)P-1 cells, was then analyzed by Western blotting. The total antioxidant activity, total superoxide dismutase activity, catalase (CAT) activity, and glutathione reductase (GR) activity were all analyzed after B(a)P treatment. Our results demonstrated that 1 µM B(a)P could induce ROS generation and lead to lipid peroxidation in A549 cells, and 23 differentially expressed proteins were identified. The expression levels of Mn SOD and the total SOD were induced at 0.1 µM and suppressed at 1 µM and 10 µM. Up-regulation of CAT and GR activity resulted in an increase in total antioxidant activity in A549 after exposure to B(a)P. These findings provide a basis for understanding the mechanisms of mitochondrial dysfunction and perturbation of antioxidant status induced by B(a)P on airway epithelial cells.

Antitumor Effects of Evodiamine in Mice Model Experiments: A Systematic Review and Meta-Analysis.

BACKGROUND: Evodiamine (EVO), an alkaloid extracted from the traditional Chinese medicine Euodia rutaecarpa, plays an important role in the treatment of cancer. This study was performed to clarify the effects of evodiamine in mice tumor model studies. METHODS: Electronic databases and search engines involved China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, and ClinicalTrials.gov databases, which were searched for literature related to the antitumor effects of evodiamine in animal tumor models (all until 1 October 2021). The evodiamine effects on the tumor volume and tumor weight were compared between the treatment and control groups using the standardized mean difference (SMD). RESULTS: Evodiamine significantly inhibited tumor growth in mice, as was assessed with tumor volume [13 studies, n=267; 138 for EVO and 129 for control; standard mean difference (SMD)= -5.99; 95% (CI): -8.89 to -3.10; I2 = 97.69%, p ≤ 0.00], tumor weight [6 studies, n=89; 49 for EVO and 40 for control; standard mean difference (SMD)= -3.51; 95% (CI): -5.13 to -3.90; I2 = 83.02%, p ≤ 0.00]. CONCLUSION: EVO significantly suppresses tumor growth in mice models, which would be beneficial for clinical transformation. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether EVO can be used in the adjuvant treatment of clinical tumor patients.

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis.

Background: Weight loss by lifestyle modification is the cornerstone therapy of non-alcoholic fatty liver disease (NAFLD). Intermittent fasting has shown favorable effects on body weight (BW) and relevant indicators of NAFLD in several reports. Objective: To estimate the effects of intermittent fasting on adults with NAFLD. Materials and methods: Literature searches were conducted on PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov from inception to May 10, 2021. Results: A total of six studies involving 417 patients with NAFLD were included. In the meta-analysis, there were significant differences in BW, body mass index (BMI), alanine aminotransferase (ALT), and aspartate transaminase (AST) between the control and fasting group. Up to now, there is no significant difference in triglycerides (TG), total cholesterol (TC), and other metabolic parameters between the two groups. Conclusions: Intermittent fasting is beneficial for weight management and liver enzyme improvement, but long-term feasibility and safety of intermittent fasting should be conducted in further studies.

A synergistic role of convalescent plasma and mesenchymal stem cells in the treatment of severely ill COVID-19 patients: a clinical case report.

Acute respiratory distress syndrome virus-2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) infection, which causes global public health emergencies, has sped widely for more than 5 months and has the risk of long-term transmission. No effective treatment has been discovered to date. In the cases we report, the patient continued to deteriorate even after administration of antiviral drugs such as lopinavir/ritonavir, interferon-α, and ribavirin, as well as intravenous injection of meropenem, methylprednisolone, and immunoglobulin. So, we infused the patient with convalescent plasma (CP), and the absolute lymphocyte count increased the next day and returned to normal on the fourth day. Followed by intravenous infusion of mesenchymal stem cells (MSCs), bilateral infiltrates were absorbed and the pulmonary function was significantly improved. We note that the intravenous infusion of CP and MSCs for the treatment of severe COVID-19 patients may have synergistic characteristics in inhibiting cytokine storm, promoting the repair of lung injury, and recovering pulmonary function. We hope to provide a reference for the research direction of COVID-19 clinical strategies.

Optimization and application of a dried blood spot-based genetic screening method for thalassemia in Shenzhen newborns.

BACKGROUND: To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China, thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots (DBS) obtained from newborn screening programs. METHODS: Firstly, the most suitable commercial DNA extraction kit for DBS was screened. Then, the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated. Finally, the thalassemia prevalence and genotype spectrum in Shenzhen were investigated in 2028 newborns using the optimized screening procedure. RESULTS: The Magentec extraction kit was best suited for the automated DBS DNA extraction system using eight 3-mm DBS discs. The neonatal thalassemia prevalence in Shenzhen was 9.12%; 6.31% α-thalassemia, 2.37% ß-thalassemia, and 0.44% α-/ß-thalassemia. CONCLUSIONS: Genetic screening based on DBS can precisely identify the thalassemia genotypes. Both α- and ß-thalassemia are widely distributed in Shenzhen newborns. Newborn genetic screening is important for establishing a comprehensive thalassemia prevention program and for public education.

Benzo(a)pyrene enhances the EMT-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1.

Benzo(a)pyrene (BaP), an important toxic component of cigarette smoke, can cause lung cancer and lead to the progression of lung cancer. In the present study, we investigated the effect of BaP on the migration of lung adenocarcinoma A549 cells. BaP (1 µM) promoted the migration of A549 cells in a time-dependent manner and upregulated the expression of the Twist family BHLH transcription factor 1 (Twist1). BaP also induced upregulation of the mesenchymal markers N-cadherin and vimentin and downregulation of the epithelial marker E-cadherin. When the expression of Twist1 was knocked down in A549 cells that were treated with BaP for 4 weeks (A549BaP-4w), the expression of Twist1 decreased, which inhibited the migration capacity of A549BaP-4w cells, the expression of N-cadherin and vimentin was downregulated and the expression of E-cadherin was upregulated. In addition, morphological observations of A549BaP-4w cells revealed that the epithelial characteristics of A549 cells became mesenchymal characteristics. When the expression of Twist1 was knocked down, the A549BaP-4w cells were transformed back to cells with epithelial characteristics. In conclusion, the results from the present study indicate that BaP enhances the epithelial-mesenchymal transition-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1.

Beneficial effects of oligopeptides from marine salmon skin in a rat model of type 2 diabetes.

OBJECTIVE: This study aimed at investigating whether treatment with oligopeptides from marine salmon skin (OMSS) could modulate type 2 diabetes mellitus (T2DM)-related hyperglycemia and ß-cell apoptosis in rats induced by high fat diet and low doses of streptozotocin and its therapeutic mechanisms. METHODS: Groups of T2DM rats were treated with OMSS or bovine serum albumin (3.0 g/kg/d) for 4 wk and their blood samples, together with those of normal control rats, were collected before and 4 wk after treatment. The levels of fasting blood glucose (FBG) and insulin, serum superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH), tumor necrosis factor-alpha (TNFα), and interferon-gamma (IFNγ) in rats were determined. The islet cell apoptosis and Fas/FasL expression were detected by TUNEL and immunohistochemistry. RESULTS: In comparison with control rats, higher levels of FBG and frequency of apoptotic islet cells were detected in the bovine serum albumin group of diabetic rats, accompanied by higher levels of Fas expression in the pancreatic islets, serum TNFα, IFNγ, and MDA, but lower levels of SOD and GSH. However, the levels of FBG and frequency of apoptotic islet cells were significantly reduced in OMSS-treated rats. Lower levels of Fas expression were observed in the pancreatic islets of OMSS-treated rats. Significantly reduced levels of serum TNFα, IFNγ, and MDA, but increased levels of SOD and GSH, were detected in OMSS-treated rats. CONCLUSIONS: Treatment with OMSS significantly reduced FBG in diabetic rats. This antidiabetic activity may be mediated by down-regulating T2DM-related oxidative stress and inflammation, protecting the pancreatic ß-cells from apoptosis.