With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

OBJECTIVE To optimize the salt-processing technology for Anemarrhena asphodeloides. METHODS Taking soaking time， stir-frying temperature， and stir-frying time as factors， Box-Behnken response surface methodology was employed to optimize the salt-processing technology of A. asphodeloides using the contents of mangiferin， neomangiferin， isomangiferin， timosaponin BⅡ， timosaponin AⅢ， timosaponin BⅢ， total flavonoids， and total saponins as evaluation indicators. The entropy weight method was applied to determine the weight of each indicator and calculate the comprehensive score. Based on the 17 sets of Box-Behnken response surface methodology results， a genetic algorithm （GA）-back propagation （BP） neural network was used to further optimize the salt-processing technology， with soaking time， stir-frying temperature， and stir-frying time as input layers and the comprehensive score as the output layer. The salt-processing parameters obtained from the two methods were validated and compared to determine the optimal salt-processing technology for A. asphodeloides. RESULTS The optimal salt-processing conditions obtained via the Box-Behnken response surface methodology were as follows： soaking time of 23 min， stir-frying temperature of 160 ℃ ， and stir-frying time of 12 min， yielding a comprehensive score of 63.370 2. The GA-BP neural network optimization resulted in the following conditions： soaking time of 24 min， stir-frying temperature of 163 ℃， and stir-frying time of 12 min， with a comprehensive score of 65.163 8. The GA-BP neural network optimization outperformed the results obtained by Box-Behnken response surface methodology. CONCLUSIONS This study successfully optimized the salt-processing technology for A. asphodeloides. Specifically， the technology involves adding 15 mL of 0.1 g/mL saline solution to 50 g of the herbal slices， allowing them to moisten for 24 minutes， and then stir-frying at 163 ℃ for 12 minutes.

ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg^-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg^-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot. ResultCompared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）. ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.

Objective:To explore the role of serum cholinesterase (CHE) levels in the prognosis of patients with acute decompensated heart failure (ADHF).Methods:Total of 244 consecutive patients with ADHF who were admitted to the emergency department and were successfully discharged were prospectively enrolled from January 2018 to June 2020. Patients were divided into groups according to the first and third quartile of CHE level and the clinical data, laboratory tests and other nutritional indices were recorded after discharge, and then were followed up. The primary end points were the composites of cardiovascular death and hospitalization for worsening HF (composite end points). The secondary end points were all-cause mortality and cardiovascular death. Cox proportional risk analysis, time-dependent Cox regression model or stratified cox regression were used to identify the risk of primary and secondary endpoints. Clinical, biomarker and the compound models of clinical and biomarker were constructed. Kaplan-Meier method was used to plot the survival curves of different groups and compare their differences. Receiver Operating characteristics (ROC) curves were used to compare the area under the curve for CHE levels and other nutritional or prognostic indicators to identify composite end-point events.Results:During a follow-up period of 350(100,683) days, 158 patients reached the composite end points. In the multivariable Cox analysis, cholinesterase level was significantly associated with the composite end points after adjustment for major confounders. Cox proportional risk analysis or time-dependent Cox regression model showed that CHE level was significantly associated with the composite end points, all-cause mortality and cardiovascular mortality in both clinical, biomarker and composite models (all P< 0.05). A Kaplan–Meier analysis revealed that patients with low cholinesterase levels had significantly greater risk of reaching the composite end points than those with middle or high cholinesterase levels (78.1% vs 66.7% vs. 46.7%, P<0.001); Cholinesterase level showed the largest area under the receiver operating characteristic curve (AUROC) of 0.736 (95% CI, 0.664-0.888) for prediction of the composite end points among other nutritional indices. The AUROC of the Global Meta-Analysis Group Chronic Heart Failure (MAGGIC) Risk Score for prediction of the composite end points was increased from 0.704 to 0.762 ( P=0.038), when cholinesterase level was added. Conclusions:Cholinesterase may serve as a simple and effective prognostic marker for predicting adverse outcomes in ADHF patients.

Objective:To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery.Methods:The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators.Results:A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR ( OR=1.467, 95% CI 1.308-1.645, P<0.001), age ( OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation ( OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin ( OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve ( AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825, P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions:For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.

Objective To investigate the efficacy and complications of one-step and two-step ultrasound-guided percutaneous transhepatic hepatic duct drainage(PTHD)in the treatment of advanced low-level biliary obstruction.Methods A total of 112 patients with advanced low-level biliary obstruction who underwent palliative surgery for reducing jaundice in the hospital from January 2019 to July 2023 were selected,and divided into the one-step group and the two-step group according to the principle of complete randomization(grouped by random number table method).The one-step group(n=56)underwent one-step PTHD,while the two-step group(n=56)underwent two-step PTHD.Surgery related indicators,serum total bilirubin(TBIL),alkaline phosphatase(ALP),alanine transaminase(ALT),the incidence of postoperative complications,and satisfaction were compared between the two groups.Results There was no difference in intraoperative blood loss[(2.96±0.50)ml vs.(3.02±0.53)ml],drainage volume in 48 hours after surgery[(555.84±90.51)ml vs.(560.52±104.23)ml]between the two groups(P＞0.05).Operation time and postoperative VAS score of the one-step group were significantly shorter/lower than those of the two-step group[(32.50±4.26)min vs.(36.43±3.58)min,(3.72±1.57)points vs.(4.53±1.34)points],and the success rate of puncture was significantly higher than that in the two-step group(96.43％vs.76.69％),with statistically significant differences(P＜0.05).After treatment,the levels of TBIL,ALP and ALT in the two groups were significantly reduced(P＜0.05),but there was no statistically significant difference between the groups(P＞0.05).There was no statistically significant difference in the incidence of complications between the two groups(3.57％vs.7.14％,Fisher's exact probability=0.679).The satisfaction rate in the one-step group was significantly higher than that in the two-step group(94.64％vs.75.00％),with a statistically significant difference(P＜0.05).ConclusionThe operation time of one-step PTHD is shorter and the success rate of puncture is higher.In addition,patients undergoing one-step PTHD have milder pain,and are more satisfied.

Objective:Care bundles for critically ill patients with early enteral nutrition up to goal was constructed. Its purpose was to improve early enteral nutrition, prognosis and provide reference basis for improving the rate of standard of early enteral nutrition in critically ill patients.Methods:By conducting systematic searching of domestic and foreign Chinese and English databases, related guide websites, relevant documents on early enteral nutrition in critically ill patients up to goal, which were obtained, evaluated, extracted, summarized and graded. After discussion by the research group, the first draft was prepared. Delphi method was used to conduct two rounds of expert correspondence, and the final draft of the proposal was established through the reliability analysis of correspondence results.Results:Twenty experts participated finally, and their opinions tended to be consistent after two rounds of expert inquiry. The authority coefficients were 0.92 and 0.91 respectively. The variation coefficients of the importance and operability of the two rounds of correspondence items were 0.05-0.20 and 0.05-0.21, 0.00-0.17 and 0.00-0.20 respectively. The Kendall concordance coefficients for the importance and operability of the two rounds of correspondence items were 0.16 and 0.13, 0.27 and 0.18 respectively. The differences were statistically significant ( χ2 values were 117.01-228.43, all P<0.05). Finally, the final draft of bundle of care for early enteral nutrition up to goal in critically ill patients was established which included three aspects related to evaluation, implementation, and effectiveness monitoring, besides care bundle included 12 intervention perspectives and 29 specific intervention measures. Conclusions:Based on evidence-based and delphi method constructing care bundles for critically ill patients with early enteral nutrition up to goal was scientific, reliable and practical which could provide theoretical and practical guidance for bundled nursing interventions to meet early enteral nutrition standards in critically ill patients.

Objective To evaluate the dynamic efficacy of Invigorating Qi and Dissipating Depression Herbs in the treatment of depressive disorders and its effect on recurrence rate and suicidal thoughts.Methods The prospective cohort study was used to divide the patients into three cohorts according to the different exposure factors(treatment regimens):Western medicine group,integrated traditional Chinese and Western medicine group,and Invigorating Qi and Dissipating Depression Herbs group,and followed up for 2 years,and the treatment effects of each cohort at half a year,one year,one and a half years,and two years were observed respectively,and the evaluation indicators were Montgomery Depression Scale(MADRS),Hamilton Anxiety Scale(HAMA)and Social Deficit Screening Scale(SDSS)reduction rates,and endpoint events(relapse,suicidal ideation)incidence;By comparing the efficacy and endpoint event rate of the three cohorts,the effect of Invigorating Qi and Dissipating Depression Herbs on improving depressive disorders was evaluated.Results A total of 409 patients(67 in the Western medicine group,131 in the integrated traditional Chinese and Western medicine group,and 211 cases in the Invigorating Qi and Dissipating Depression Herbs group)were enrolled,and the rate of score reduction after treatment with MADRS,HAMA and SDSS increased compared with the pre-treatment treatment with the extension of the drug taking time.The difference between the MADRS and SDSS reduction rates in the Invigorating Qi and Dissipating Depression Herbs group on taking the drug for half a year and the SDSS reduction rate on one year of taking the drug were statistically significant compared with the Western medicine group,and there was no significant difference compared with the integrated Chinese and Western medicine group.On one and a half years and two years of medication,the integrated Chinese and Western medicine group had more advantages in MADRS reduction rate than the Invigorating Qi and Dissipating Depression Herbs group.The recurrence rates of depression in the three groups within 2 years were 20.9％,30.5％and 36.0％,and the difference was not statistically significant,and the length of taking medication was used as a protective factor by logistic regression analysis.The incidence rates of suicidal thoughts were 44.8％,19.1％and 17.5％,and the differences were statistically significant,and the exposure factors and income level were the protective factors by logistic regression analysis.Conclusion Invigorating Qi and Dissipating Depression Herbs can significantly improve the depressive state of patients,promote the recovery of social function,reduce the occurrence of long-term suicidal ideation,and appropriately extend the time of taking medicine can increase the long-term efficacy and reduce recurrence.

Humans ; Stroke/therapy* ; Thrombectomy ; Treatment Outcome ; Brain Ischemia/therapy* ; Retrospective Studies