Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

OBJECTIVES: To investigate the role of circular RNA circ_0000437 in regulating biological behaviors of breast cancer cells and the molecular mechanism. METHODS: Breast cancer MCF-7 and MDA-MB-231 cells were transfected with sh-circ_0000437, mimics, inhibitor, si-CTPS1, or their respective negative controls. qRT-PCR was used to detect the expression levels of circ_0000437, let-7b-5p, CTPS1, Notch1, Hes1, and Numb in breast cancer cell lines and tissues. RNase R digestion was used to confirm the circular structure of circ_0000437 and its subcellular localization in the breast cancer cells was determined by cellular distribution analysis. The changes in proliferation, invasion and migration of the transfected cells were assessed using CCK-8 assay, Transwell assay and scratch assay. Dual-luciferase reporter gene and RNA immunoprecipitation assays were employed to validate binding interactions among circ_0000437, let-7b-5p, and CTPS1. The cellular expressions of CTPS1, E-cadherin, N-cadherin, and vimentin proteins were detected with Western blotting. A tumor-bearing mouse model was used to verify the oncogenic mechanism of circ_0000437 and CTPS1. RESULTS: Circ_0000437 and CTPS1 were upregulated while let-7b-5p was downregulated in breast cancer tissues and cell lines. Circ_0000437 or CTPS1 knockdown obviously suppressed breast cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT). Overexpression of let-7b-5p produced similar inhibitory effects, whereas inhibition of let-7b-5p significantly enhanced malignant behaviors of the cells. In the tumor-bearing mouse models, circ_0000437 knockdown significantly suppressed tumor growth, but co-transfection of the cells with pcDNA-CTPS1 accelerated tumor growth. Binding sites were identified between circ_0000437 and let-7b-5p and between let-7b-5p and CTPS1, and circ_0000437, let-7b-5p, and CTPS1 showed functional interactions in breast cancer cells. CONCLUSIONS Circ_0000437 is upregulated in breast cancer tissues and cells, and its high expression promotes proliferation, invasion, migration and EMT of breast cancer cells through the let-7b-5p/CTPS1 axis.
Humans ; Epithelial-Mesenchymal Transition ; Cell Proliferation ; MicroRNAs/metabolism* ; RNA, Circular ; Breast Neoplasms/metabolism* ; Cell Movement ; Female ; Neoplasm Invasiveness ; Cell Line, Tumor ; MCF-7 Cells ; Animals ; Mice

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

To explore the pathogenesis of type 2 diabetes mellitus(T2DM)based on the trinity life view of physique-qi-spirit,and point out that the occurrence and development of T2DM are the three elements of life,i.e.physique,qi and spirit,which have patho-logical changes.This paper discusses from three aspects:physique,qi,and spirit.The changes in physique include structural chan-ges,abnormal physical movements,and changes in tangible and subtle substances;the changes in qi include qi deficiency and abnor-mal qi transformation;the changes in spirit include carnal desire excess and emotional imbalance.This paper provides new ideas for the clinical diagnosis and treatment of T2DM.

Objective To compare the cost and utility of aflibercept and conbercept for the treatment of wet age-related macular degeneration(wetAMD),in order to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods The incremental cost-utility ratio(ICUR)was obtained by using Markov model to simulate the survival of the two treatment regimens over the 5-year period,calculating costs and health outputs separately.Univariate sensitivity analysis was used to determine the impact of the parameter on ICUR,and probability sensitivity analysis was used to determine the influence of the uncertainty of each model parameter on the research results.One times the 2022 gross domestic product(GDP)per capita of China was used as the willingness-to-pay threshold(WTP)to judge its economy.Results Over the simulation period,the compazine regimen was significantly economical against the aflibercept regimen,with an ICUR of-1 528 840 per quality-adjusted life year(QALY),which was lower than the WTP.Univariate sensitivity analysis showed that the transition probability between mild and moderate visual status between the two regimens and the number of aflibercept injections per year were significant influencing factors of ICUR.Probabilistic sensitivity analysis pointed to a significant cost-utility advantage for conbercept at a WTP of one times GDP(probability of 65.9％),which was a more robust result.Conclusion For the treatment of wetAMD,conbercept has a cost-utility advantage compared with aflibercept.

ObjectiveIn view of the problems of large errors and poor accuracy in pulmonary function testing in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a predictive classification model of pulmonary function in patients with AECOPD was proposed by comparing the prediction performance of different machine learning models to find the optimal model. MethodsFrom January, 2018 to February, 2020, 90 patients with different degrees of COPD from the Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University were collected. Six machine learning model algorithms (K-nearest neighbor, logistic regression, support vector machine, naive Bayes, decision tree and random forest) were used to establish AECOPD predictive classification models. Their area under the curve of receiver operating characteristic (AUC-ROC) and accuracy were compared. Ten-fold cross-validation method was used to validate the data set. ResultsThe model based on random forest worked best in predicting and classifying AECOPD patients, with an accuracy rate of 0.844 and an AUC-ROC of 0.916. ConclusionRandom forest-based predictive model is a powerful tool for identifying patients with AECOPD, providing decision support when it is difficult to give a definitive diagnosis.

Objective:To evaluate the outcomes of posterior-column dominating three-column tibial plateau fractures treated by raft-nailing and cannulated screwing via the posteromedian approach.Methods:From October 2017 to June 2019, 15 patients with posterior-column dominating three-column tibial plateau fracture were surgically treated at Department of Orthopedics, The First Affiliated Hospital to Harbin Medical University. They are 11 males and 4 females, aged from 26 to 65 years (average, 41.2 years). All patients were operated on under general anesthesia or spinal anesthesia. After full exposure via the posteromedian approach using a popliteal S-shaped incision, their fractures were treated with raft-nailing and cannulated screwing. Wound healing and neurovascular injury were observed after operation. X-ray films were taken regularly to monitor fracture union and measure the tibial plateau angle (TPA) and posterior slope angle (PA) of the tibial plateau. The knee function was assessed using The Hospital for Special Surgery (HSS) scoring system at 12 months after operation.Results:Incisions healed by the first intention after surgery in 14 patients but the healing was delayed due to fat liquefaction in one patient. No symptoms of neurovascular injury were observed in the 15 patients who were followed up for 12 to 29 months (average, 16.5 months). All fractures united after 12 to 20 weeks (average, 15.4 weeks). At 3 days and 12 months after operation, respectively, their PA was 9.3°±2.1° and 9.7°±1.6° and their TPA 4.3°±1.2° and 4.1°±1.1°, showing no significant difference ( P>0.05). At 12 months after operation, their HSS scores ranged from 84 to 95 (average, 89.3), their knee flexion from 105° to 138° (average, 126.5°) and their knee extension from 0° to 8° (average, 3.4°). Conclusions:In the treatment of posterior-column dominating three-column tibial plateau fractures, raft-nailing combined with cannulated screwing via the posteromedian approach can achieve not only full exposure by a single incision but also stable plateau fixation, reduce operative invasion, and simplify operative procedures, leading to fine surgical outcomes.

Objective:To explore therapeutic effect of rosuvastatin combined clopidogrel bisulfate tablet on patients with coronary heart disease (CHD).Methods: A total of 124 patients, who were diagnosed as CHD by coronary angiography, were selected, randomly and equally divided into routine treatment group (received routine treatment,including clopidogrel bisulfate tablet) and combined treatment group (received rosuvastatin based on routine treatment group), both groups were treated for six months.Cardiac function, serum levels of angiotensin II (Ang II), vascular endothelial growth factor (VEGF) and nitric oxide (NO), and therapeutic effect were measured and compared between two groups before and after treatment.Results: Total effective rate of combined treatment group was significantly higher than that of routine treatment group (96.77% vs.83.87%, P=0.015).Compared with routine treatment group after treatment, there were significant rise in left ventricular ejection fraction [(61.89±7.02)% vs.(68.96±8.23)%] and NO level [(75.25±9.45) μmol/L vs.(82.25±10.22) μmol/L], and significant reductions in wall motion score index [(1.35±0.39)% vs.(1.11±0.29)%], levels of Ang Ⅱ [(102.25±6.93) ng/L vs.(52.99±5.36) ng/L] and VEGF [(328.25±23.41) ng/L vs.(228.69±22.69) ng/L] in combined treatment group, P<0.01 all.Conclusion: Rosuvastatin combined clopidogrel bisulfate tablet can effectively improve heart function, serum levels of Ang II, VEGF and NO in patients with coronary heart disease, the therapeutic effect is significant, which is worth extending.

Objective To observe the curative effect of traditional Chinese medicine (TCM) Gubiao Pixie prescription on the prevention of nosocomial infection in elderly patients with susceptible factors.Methods A prospective observational study was conducted. The elderly patients aged over 70 years admitted to the Department of Integrated TCM and Western Medicine of Tianjin First Center Hospital from March 2015 to March 2016 were enrolled. The patients were divided into experiment group and control group by random number table. The patients in control group were given conventional treatment without special intervention; and those in experimental group were given Gubiao Pixie prescription particles (prescription composition:Radix Astragali 30 g,Bran fried Rhizoma Atracylodis 20 g,Raidix Saposhnikoviae 12 g,Radix Scutellariae 10 g,Fructus Tsaoko 6 g) on the basis of conventional treatment. The Gubiao Pixie prescription particles were taken in warm water 300 mL, twice a day in morning and evening respectively, taking half an hour after meals, and were increased or decreased according to the disease condition. The changes in immune function parameters before and after treatment, as well as the incidence of nosocomial infection, the abnormal increase rate of body temperature, white blood cell (WBC), and C-reactive protein (CRP) after 10 days of treatment in the two groups were observed.Results A total of 110 elderly patients with susceptible factors during hospitalization were included. After the exclusion of vomiting, abdominal distension and failure to conform the trial requirements, hospitalization time less than 10 days of patients, a total of 100 patients were enrolled in the analysis finally, with 50 patients in control group and in experimental group respectively. There were no significant differences in immune function parameters including IgA, IgG, IgM before treatment between the two groups. After 10 days of treatment, the immune function parameters showed no significant improvement in control group, and those in experiment group were improved significantly, and IgA (g/L: 1.59±0.32 vs. 1.29±0.29), IgG (g/L: 12.07±2.37 vs. 10.23±1.91), and IgM (g/L: 1.01±0.29 vs. 0.88±0.24) were significantly increased as compared with those of control group (allP < 0.01). Compared with the control group, the incidence of nosocomial infection (20% vs. 38%) and the abnormal increase rate of body temperature (24% vs. 44%), WBC (28% vs. 52%), and CRP (28% vs. 50%) 10 days after treatment in experimental group were significantly decreased (allP < 0.05).Conclusions TCM Gubiao Pixie prescription has a role in enhancing immune function and antibacterial and bactericidal effect. It has certain preventive effect on nosocomial infection in susceptible people.

Objective To investigate the epidemiological trend of human intestinal helminth infections in Yancheng City,Ji?angsu Province from 2006 to 2015,so as to provide the evidence for formulating further control strategies. Methods The sur?veillance data of human intestinal helminth infections were collected and analyzed in Yancheng City from 2006 to 2015. Re?sults From 2006 to 2015,110 746 person?times of residents in Yancheng City were surveyed in Yancheng City,and 1 732 samples were positive of human intestinal helminth infections. The infection rate of human intestinal helminthes was highest in 2006[4.59%(410/8 941)],and lowest in 2013[0.19%(23/12 165)]. The infection rate of human intestinal helminthes was significantly decreased over time(χ2=27.78,P<0.001). The human infection rates of Ascaris lumbricoides,hook worm and Trichuris trichura were all decreased over time(Z=-27.75,-22.23 and-16.17,all P<0.001)from 2006 to 2015,with the re?duction rates of 96.57%,92.31%and 96.47%,respectively. The average EPG of A. lumbricoides,hook worm and T. trichura were 2 534,360 and 154 respectively,and 1 694(97.81%)cases were light infections. Totally 1 174 cases of Enterobius vermic?ularis were found in children under 12 years old,and the cases were decreased over time(χ2 =12.46,P<0.001). Conclu?sions The infection rate of human intestinal helminthes in Yancheng City decreases over time from 2006 to 2015,and the con?trol work is effective. The control work of focus groups and environmental management and health education should be strength?ened in the future.