Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.

Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.

Neurocutaneous syndrome is a multi-system disease involving the nervous system and skin,with onset in various forms and typically in infancy,which are difficult to cure with a poor prognosis.The etiology of neurocutaneous syn-drome is complex,mostly caused by gene mutations,including heritable mutations and occasionally non-hereditary postzy-gotic somatic mutations.Cases of different types of neurocutaneous syndrome have been reported,such as Sturge-Weber syndrome,tuberous sclerosis,and neurofibromatosis.Specific medications are lacking among current therapeutic ap-proaches including symptomatic treatment,drug therapy,chemoradiotherapy,surgery,and physical therapy.With the in-creasing understanding of the pathogenesis and progress in drug research and development,new drugs could be on the hori-zon.Remarkable evidence in the field of genetic diseases suggests that gene therapy may hold promise as a treatment for neurocutaneous syndrome through fixing the pathogenic gene defects.Considering the lack of systematic review on the rare and diverse conditions,we summarize relevant studies to provide a reference for clinical workers in the diagnosis and treat-ment of neurocutaneous syndrome.

Smoking is a major concern in today's society,and the nicotine in tobacco is the major cause of addiction and difficulty in withdrawal.Long-term use of nicotine not only results in abnormal neural oscillations in the brain,but also impairs reward circuits as well as emotion regulation,thus reducing neuroplasticity and increasing susceptibility to addiction.As electrophysiological signals,electroencephalogram(EEG)signals are associated with a variety of states including cognitive function,emotion regulation,inhibitory control,and sleep.The researches on nicotine addiction reveal that changes in EEG signals are associated with abnormalities in cognitive function and inhibitory control in nicotine addicts.Therefore,exploring the abnormal neural oscillation patterns of nicotine addicts through EEG-related techniques can deepen the understanding of the intrinsic neural mechanisms of nicotine addiction and provide a scientific basis for the intervention and treatment of nicotine addiction.Herein the study summarizes the research achievements of scholars at home and abroad in recent years from the aspects of the application status of EEG in nicotine addiction researches as well as the current technology.It is found that nicotine addicts have obvious abnormalities in sleep quality,cognitive function and inhibitory control.In addition,the functional brain connectivity,event-related potentials and EEG power spectra of addicts are significantly changed.Finally,an outlook on the research prospects of EEG signals in nicotine addiction is provided,emphasizing the potential applications of EEG signals in addiction mechanisms,withdrawal responses,and assessment of treatment efficacy.

Smoking is a major concern in today's society,and the nicotine in tobacco is the major cause of addiction and difficulty in withdrawal.Long-term use of nicotine not only results in abnormal neural oscillations in the brain,but also impairs reward circuits as well as emotion regulation,thus reducing neuroplasticity and increasing susceptibility to addiction.As electrophysiological signals,electroencephalogram(EEG)signals are associated with a variety of states including cognitive function,emotion regulation,inhibitory control,and sleep.The researches on nicotine addiction reveal that changes in EEG signals are associated with abnormalities in cognitive function and inhibitory control in nicotine addicts.Therefore,exploring the abnormal neural oscillation patterns of nicotine addicts through EEG-related techniques can deepen the understanding of the intrinsic neural mechanisms of nicotine addiction and provide a scientific basis for the intervention and treatment of nicotine addiction.Herein the study summarizes the research achievements of scholars at home and abroad in recent years from the aspects of the application status of EEG in nicotine addiction researches as well as the current technology.It is found that nicotine addicts have obvious abnormalities in sleep quality,cognitive function and inhibitory control.In addition,the functional brain connectivity,event-related potentials and EEG power spectra of addicts are significantly changed.Finally,an outlook on the research prospects of EEG signals in nicotine addiction is provided,emphasizing the potential applications of EEG signals in addiction mechanisms,withdrawal responses,and assessment of treatment efficacy.

This study explores the application effect of the case-based teaching method based on Xuexitong learning platform in the online teaching of Digestive System, and analyzes the learner's emotional experience, learning behavior, and learning effect in the case-based online teaching. The results of the study show that the case-based online teaching model based on Xuexitong learning platform improves students' online learning interest, and the students have good emotional experience, high learning enthusiasm, good classroom interaction, enhanced self-learning ability before and after class, and good learning effect. In addition, precise teaching can be used for individual students who are not enthusiastic about online learning.

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

Objective To investigate the correlation between plasma cystatin C (CysC) level and carotid atherosclerotic plaque in patients with ischemic stroke.Methods The clinical data in patients with acute ischemic stroke were analyzed retrospectively.According to the results of carotid artery ultrasound,the patients were divided into either a non-plaque group or a plaque group.Then the plaque group was redivided into a stable plaque subgroup and a vulnerable plaque subgroup.Multivariate logistic regression analysis and Pearson correlation analysis were used to explore the risk factors for carotid atherosclerotic plaque.Results A total of 226 patients with acute ischemic stroke were enrolled,172 of them had carotid plaque,and 54 had no plaque.Of the patients with carotid plaque,94 were stable plaque and 78 were vulnerable plaque.The age (71.82 ± 9.94 years vs.60.74 ± 13.81 years; t =6.160,P =0.014),proportion of patients with ischemic heart disease (11.6％ vs.1.9％; x2=6.169,P=0.020),systolic blood pressure (148.770± 21.007 mm Hg vs.142.240 ± 19.404 mm Hg; t =2.029,t =0.044),plasma CysC concentration (1.046 ± 0.438 mg/L vs.0.860 ±0.214 mg/L; t =3.006,P =0.003),and carotid IMT (1.122 ±0.278 mm vs.0.878 ±0.250 mm; t =5.762,P=0.000) in the plaque group were significantly higher than those in the non-plaque group.Multivariate logistic regression analysis showed that the age (odds ratio [OR] 1.079,95％ confidence interval [CI] 1.044-1.116; P=0.000) and IMT (OR 31.450,95％ CI 6.233-158.692; P=0.000) was the independent risk factor for carotid plaque,while there was no significant independent correlation between the plasma CysC level and carotid plaque (P =0.217).Only IMT in the stable plaque subgroup was significantly higher than the vulnerable plaque group (1.176 ±0.285 mm vs.1.058 ±0.258 mm; t =-2.824,P =0.005),and it was the independent protective factor for the carotid plaque stability (OR 0.195,95％ CI 0.059-0.064; P =0.007).Pearson correlation analysis showed that the plasma CysC level was positively correlated with the age (r =0.375,P =0.000) and serum creatinine level (r =0.462,P =0.000),but it was not significantly correlated with carotid IMT (r =0.075,P =0.264).Conclusions In patients with ischemic stroke,no correlations were found between the plasma CysC level and carotid atherosclerotic plaque,plaque stability,and IMT.

OBJECTIVETo develop a high performance liquid chromatography coupled with a photodiode array detector (HPLC-DAD) method for simultaneous determination of 7 nucleosides and nucleobases in Fritillaria taipaiensis.

METHODThe analyses were performed on an Agilent Zorbax-SB-Aq-C18 column (4.6 mm x 250 mm, 5 microm) eluted with water and methanol in gradient mode. The flow rate was 1.0 mL x min(-1). The detection wavelength was 260 nm. The temperature of sample manager was set at 25 degrees C, and the injection volume was 20 microL.

RESULTThe investigated compounds including uracil, cytidine, uridine, guanosine, thymidine, adenosine and adenine were shown good linearity (r > or = 0.999 8) over the tested ranges. The average recoveries were within 96.96% - 103.5% with RSD < or = 3.8%.

CONCLUSIONThe accuracy, stability, repeatability and average recovery of the method are satisfying, and the seven nucleosides and nucleobases components in F. taipaiensis can be rapidly and accurately quantified by HPLC-DAD. This work provided helpful information for comprehensive quality evaluation of F. taipaiensis.

Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Fritillaria ; chemistry ; Nucleosides ; analysis ; Reproducibility of Results ; Water ; chemistry