Zhiyi Wang

Metabolic changes in rat urine after acute paraquat poisoning and discriminated by support vector machine

Paraquat is quick-acting and non-selective, killing green plant tissue on contact; it is also toxic to human beings and animals. In this study, we developed a urine metabonomic method by gas chromatography-mass spectrometry to evaluate the effect of acute paraquat poisoning on rats. Pattern recognition analysis, including both partial least squares discriminate analysis and principal component analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the levels of benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group (intragastric administration 36 mg/kg) increased, while the levels of butanedioic acid, pentanedioic acid, altronic acid decreased. Based on these urinary metabolomics data, support vector machine was applied to discriminate the metabolomic change of paraquat groups from the control group, which achieved 100% classification accuracy. In conclusion, metabonomic method combined with support vector machine can be used as a useful diagnostic tool in paraquat-poisoned rats.

The role of propionic acid at diagnosis predicts mortality in patients with septic shock.

Purpose: This study aims to assess the diagnostic and prognostic value of propionic acid in patients with septic shock on a medical intensive care unit (ICU). Methods: Serum propionic acid and clinical common cytokines levels were measured within 24 h after the diagnosis of sepsis, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, and Mortality were recorded in ICU. A 28‐day and 90‐day follow‐up was performed for all patients. Results: A total of 118 septic patients were enrolled in this study. The propionic acid was higher in patients with septic shock compared with sepsis. Multivariate logistic regression analysis showed that propionic acid was independent predictor of sepsis (odds ratio: 1.279; 95% confidence interval: 1.069–1.530; P = 0.007) and septic shock (odds ratio: 1.859; 95% confidence interval: 1.342–2.576; P < 0.001) and ICU mortality (odds ratio: 1.331; 95% confidence interval: 1.107–1.600; P = 0.002), 28‐day mortality (odds ratio: 1.259; 95% confidence interval: 1.046–1.514; P = 0.015) and 90‐day mortality (odds ratio: 1.304; 95% confidence interval: 1.092–1.558; P = 0.003). The receiver operating characteristic curve (AUC) analysis showed the areas under of propionic acid on ICU admission day for predicting sepsis and septic shock were 0.773 and 0.85 respectively, the areas under of propionic acid for predicting ICU mortality, 28‐d and 90‐d mortality were 0.779, 0.739 and 0.809 respectively. Using a PA cutoff of 0.053 and 0.095 for predicting sepsis and septic shock respectively, the sensitivity was 97.62% and 85.5%, and the specificity was 58% and 83.5%, respectively. Using a PA cutoff of 0.139 for predicting ICU mortality, 28‐ and 90‐day mortality, the sensitivity was 69.39%, 67.44% and 69.09% respectively, and the specificity was 78.26%, 73.33% and 82.54% respectively. Conclusions: Propionic acid showed diagnostic capacity to diagnose septic shock and revealed prognostic information for mortality.

Serum Metabolomics in Rats after Acute Paraquat Poisoning

Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers.

Comparative study of two perfusion routes with different flow in decellularization to harvest an optimal pulmonary scaffold for recellularization

Decellularization processes may variably distort or degrade extracellular matrix (ECM) structure. In this study, two perfusion routes (PR) were tested on SD rat lung samples. One decellularization protocol, PR1, was perfused through the pulmonary artery. The other decellularization protocol, PR2, was perfused through the trachea. Both decellularization protocols were used by the same detergent-based (sodium dodecyl sulphate and Triton X-100) with different flow continuous perfusion. There was no visible difference in vessel architecture between PR1- and PR2-decellularized scaffold. However, the airway structure and alveoli architecture of pulmonary decellularized scaffolds generated through PR2 at a flow rate of 8 mL/min were destroyed partly when compared to that in native lung and PR1-decellularized scaffold. Ultramicroscopic assessment of scaffolds was similar in both protocols and showed filamentous ECM with preserved fiber disposition and structure. Histological analysis and immunostaining showed no detectable cells remaining in the pulmonary scaffolds compare with native lung. The DNA concentration was significantly reduced in the decellularized scaffolds compared to the native lungs. A549 cells reseeded onto decellularized pulmonary scaffolds were no significant difference between PR1 and PR2 in cell viability, p > 0.05. We conclude that under the same high flow velocity status, perfusion decellularization through the pulmonary artery may be an optimal pathway to obtain decellularized scaffolds for pulmonary regeneration. This article is protected by copyright. All rights reserved.

Risk Factors for Early Postoperative Small Bowel Obstruction after Anterior Resection for Rectal Cancer: Methodological Issues

Dear Editor, We were interested to read the paper authored by Suwa and colleagues published in the World Journal of Surgery in 2017 [1]. Their study was to assess the risk factors for small bowel obstruction (SBO) in early postoperative period after anterior resection (AR) for rectal cancer. The results provide evidence that the D3 lymph node dissection and DI formation are independent risk factors for EPSBO in AR [1]; however, some methodological issues should be noticed. In this study, multivariate analysis was performed using the factors that were considered significant in the univariate analysis (factors with p values less than 0.05). The risk factors with p values less than 0.05 which have large effect on outcome and p values less than 0.2 may have a relatively small effect on outcome. If we selected only those with p value\0.05 in multivariable analysis, the effect of such predictors will be overestimated and in following the prediction power will be decreased. So, independent variables with p values less than 0.2 should be selected to be imported into the multivariable model. Otherwise, it can induce testimation bias in the results [2]. In the study, some odds ratios (ORs) and CIs were relatively large such as 17.25 (3.49–312.55) for low anterior resection and 13.61 (2.75–246.69) for D3 lymph node dissection in Table 2. This is probably due to the multicollinearity [2]. Although, the authors have mentioned it in their study, the multivariate model may be affected by bias because of the multicollinearity [2]. The authors concluded that D3 lymph node dissection and DI formation are independent risk factors for early postoperative SBO in AR. However, the prediction models were not be validated through using some appropriate methods such as cross-validation and bootstrapping, otherwise, these results would be optimistic interpretation. Correcting optimism problem in study with small sample size have been more emphasized [3].

Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy: Methodological issues

Dear Editor, Wewere interested to read the article “Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy” published in Journal of Surgical Oncology recently, which shows an incidence of 28% of delirium, occurring after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and suggests a role for systemic inflammation in the development of postoperative delirium. Although the results were interesting, some methodological issues should be noticed. In the study, some odds ratios (ORs) and CIs were relatively large such as 18.19 (2.11-156.82) for sepsis in Table 3. This is probably due to the multicollinearity. So, the multicollinearity between independent variables must be initially examined. Otherwise, regression model may be affected by bias because of the multicollinearity. The authors concluded that surgery extensiveness and serum level of CRP were independent predictors for delirium postoperatively. However, the prediction models were not be validated through using some appropriatemethods such as cross-validation and bootstrapping, otherwise, these results would be optimistic interpretation. Correcting optimism problem in study with small sample size have been more emphasized.

Metabolic changes in methomyl poisoned rats treated by vitamin E

In this study, we developed a serum and urine metabolomic method based on gas chromatography–mass spectrometry (GC-MS) combination with biomedical results to evaluate the effect of vitamin E treatment on methomyl poisoning rats. The rats were divided into three groups: the control group, methomyl poisoning group, and vitamin E treatment group. Partial least squares discriminate analysis (PLS-DA) showed that methomyl poisoning induced metabolic perturbations. Compared to the control group, based on the urinary metabolomics data, the level of ribitol, l-proline, xylitol, hydrocinnamic acid, 11-cis-octadecenoic acid, octadecanoic acid, and hexadecanoic acid of methomyl poisoning group increased, while the level of 2,3,4-trihydroxybutyric acid, ethanimidic acid, pantothenic acid, and retinoic acid decreased. Vitamin E pretreatment effectively normalized the levels of metabolites in rat urine in vitamin E treatment group. There was no significant difference in rat plasma metabolomic data after acute methomyl poisoning. The results indicate that metabolomic method based on GC-MS may be useful to elucidate the vitamin E treatment for methomyl poisoning.

Amiodarone induces epithelial-mesenchymal transition in A549 cells via activation of TGF-β1

Abstract Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal transition (EMT) was a significant process in pulmonary fibrosis. So far, there are no studies about whether EMT was associated with amiodarone-induced pulmonary fibrosis, which was therefore explored in this study. In addition, the underlying mechanisms of amiodarone-induced pulmonary fibrosis were examined in vitro. We found the EMT marker (α-SMA) was significantly increased, while the E-cadherin was significantly decreased in adenocarcinomic human alveolar basal epithelial cells (A549) after amiodarone treatment, suggesting that the epithelial cells were an important source of mesenchymal cells. Transforming growth factor beta1 (TGF-β1) was also increased significantly after amiodarone treatment. In conclusion, this study suggested amiodarone could induce pulmonary fibrosis via EMT, and the TGF-β1 may be a key profibrotic cytokine in mechanisms of amiodarone-induced pulmonary fibrosis.

Risk factors for postoperative ileus after colorectal cancer surgery: methodological issues

We read the study by Rybakov and colleagues [1] in which the authors assess the rate and independent risk factors for postoperative ileus (POI) after colorectal cancer surgery. The results provide evidence of at least two surgeon-dependent risk factors, i.e. open approach and opioids in the postoperative period. Although the study was interesting, some methodological points need to be taken into account. This article is protected by copyright. All rights reserved.

Letter to the Editor: Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone

• The factors with P values <0.2 in the univariate analysis should be proceeded to the multivariate analysis.