ObjectiveThis study aims to explore the neurotoxicity mechanism of Dictamni Cortex by integrating network toxicology and metabolomics techniques. MethodsThe neurotoxicity targets induced by Dictamni Cortex were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCM-ID）， and Comparative Toxicogenomics Database （CTD）. The target predictions of the components were performed by the Swiss Target Prediction tool. Neurotoxicity-related targets were collected from the Pharmacophore Mapping and Potential Target Identification Platform （PharmMapper）， GeneCards Human Gene Database （GeneCards）， DisGeNET Disease Gene Network （DisGeNET）， and Online Mendelian Inheritance in Man （OMIM）， and the intersection targets were identified. Protein-protein interaction （PPI） analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and Gene Ontology （GO） enrichment analysis were conducted. A "drug-compound-toxicity target-pathway" network was constructed via Cytoscape software to display the core regulatory network. Based on the prediction results， the neurotoxicity mechanism of Dictamni Cortex in mice was verified by using hematoxylin-eosin （HE） staining， Nissl staining， enzyme-linked immunosorbent assay （ELISA）， quantitative real-time fluorescence polymerase chain reaction （Real-time PCR）， and Western blot. The effects of Dictamni Cortex on the metabolic profile of mouse brain tissue were further explored by non-targeted metabolomics. ResultsNetwork toxicology screening identified 13 compounds and 175 targets in Dictamni Cortex that were related to neurotoxicity. PPI network analysis revealed that serine/threonine-protein kinase （Akt1） and tumor protein 53 （TP53） were the core targets. Additionally， GO/KEGG enrichment analysis indicated that Dictamni Cortex may regulate the phosphatidylinositol 3-kinase （PI3K）/Akt pathway and affect oxidative stress and cell apoptosis， thereby inducing neural damage. The "Dictamni Cortex-compound-toxicity target-pathway-neural damage" network showed that dictamnine， phellodendrine， and fraxinellone may be the toxic compounds. Animal experiments showed that compared with those in the blank group， the hippocampal neurons in the brain tissue of mice treated with Dictamni Cortex were damaged. The level of superoxide dismutase （SOD） and acetylcholine （ACh） in the brain tissue was significantly reduced， while the content of malondialdehyde （MDA） was significantly increased. The level of Akt1 and p-Akt1 mRNAs and proteins in the brain tissue was significantly decreased， while the level of TP53 was significantly increased. Non-targeted metabolomics results showed that Dictamni Cortex could disrupt the level of 40 metabolites in mouse brain tissue， thereby regulating the homeostasis of 13 metabolism pathways， including phenylalanine， glycerophospholipid， and retinol. Combined analysis revealed that Akt1， p-Akt1， and TP53 were significantly correlated with phenylalanine， glycerophospholipid， and retinol metabolites. This suggested that Dictamni Cortex induced neurotoxicity in mice by regulating Akt1， p-Akt1， and TP53 and further modulating the phenylalanine， glycerophospholipid， and retinol metabolism pathways. ConclusionDictamni Cortex can induce neurotoxicity in mice， and its potential mechanism may be closely related to the activation of oxidative stress， inhibition of the PI3K/Akt signaling pathway， and regulation of phenylalanine， glycerophospholipid， and retinol metabolism pathways.

ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)

Objective To explore the mechanism of acute liver injury induced by Cortex dictamni through network pharmacology and in vivo experiment in animal.Methods The chemical constituents and targets of Cortex dictamni were retrieved from TCMSP,TCMIP and SwissTargetPrediction databases,and the related targets of liver injury diseases were identified through GeneCards and CTD databases.The protein interaction network of the intersection targets was analyzed by STRING database and the core targets were selected.The GO function and KEGG pathway enrichment analysis were completed by DAVID database,and the multi-level association network diagram of"drug-component-target"was constructed by Cytoscape software.In the animal study,Cortex dictamni was administered to mice at a dosage of 92.7 g/(kg·d)via intragastric administration,and the biological samples were collected after 7 days.The pathological changes of liver were observed by hematoxylin-eosin(HE),Masson and Oil Red O staining.The expression levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in serum,as well as malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin(IL)-1β in liver tissues,were quantified using enzyme-linked immunosorbent assay(ELISA).The expressions of protein kinase B1(AKT1),IL-6,TNF-α,tumor protein p53(TP53),cystatin 3(CASP3),and IL-1β mRNA in liver tissues were determined using real-time quantitative reverse transcription PCR(qRT-PCR).Molecular docking was employed to verify the binding affinity of potentially toxic components to their respective targets.Results A total of 14 chemical constituents,244 predicted targets and 202 intersection targets with liver injury were obtained.The GO biological process analysis mainly involved positive regulation of gene expression,negative regulation of apoptosis process.KEGG pathway enrichment analysis mainly included cancer pathway and PI3K-Akt,TNF,IL-17 signaling pathways.The pathological sections revealed severe hemorrhage,a considerable amount of hepatocyte necrosis,nuclear fragmentation or dissolution in the liver tissues of mouse with HE staining after the administration of Cortex dictamni.Masson staining showed evident fibrosis in the liver tissues,while Oil Red O staining indicated a substantial production of lipid droplets.Compared with the control group,the ELISA results demonstrated a significant increase in serum AST,ALT,ALP,LDH levels,as well as hepatic MDA,TNF-α,and IL-1β levels(P<0.05),and a decrease in hepatic SOD levels(P<0.05)in the treated group.The qRT-PCR results indicated a significant elevation in the expression levels of relevant mRNAs in the liver tissues of the treated mice(P<0.05).Molecular docking showed that the potentially toxic components of obacunone,dictamnine and fraxinellon had good binding affinity to AKT1,IL-6,TNF-α,TP53,CASP3 and IL-1β.Conclusion Obacunone,dictamnine,fraxinellon,and limonin might be the potential toxic components of acute liver injury induced by Cortex dictamni in mice.Cortex dictamni could act on the liver by changing the expressions of AKT1,IL-6,TNF-α,TP53,CASP3,IL-1β and other proteins,affecting energy metabolism,cell differentiation,inflammation,oxidative stress and immunity,leading to liver injury.

Dictamni cortex is the root bark of Rutaceae plants.It is the main medicinal part and the key drug of 'Zhuhuang Fengbi'.It has the effects of clearing heat and detoxifying,dispelling wind and drying dampness,and relieving itching.Dictamni cortex mainly contains 228 chemical components such as alkaloids,sesquiterpenes,limonoids,fatty acids,volatile oils,flavonoids,steroids,etw.Its pharmacological activities in vivo and in vitro include antibacterial activity,anti-inflammatory activity,hepatoprotective activity,cardiovascular protection activity,insecticidal activity,anticancer activity,anti-allergic activity,and improvement of gastrointestinal activity.It has been reported that Dictamni cortex also has potential hepatotoxicity,among which dictamnine,fraxinellone and limonin compounds are potential hepatotoxic components.In this paper,the chemical constituents,pharmacological effects and toxicity of Dictamni cortex are reviewed by consulting domestic and foreign literature,to provide theoretical support for the clinical rational application and related product development of Dictamni cortex.

Bupleuri radix is the dried root of Bupleuri radix or narrow-leaved Bupleuri radix of the umbelliferae family,and it is the most commonly used traditional Chinese medicine,which was first published in Shennong's Classic of Materia Medica.It has a variety of pharmacological effects such as anti-inflammatory,antioxidant,hepatoprotective,antitumor,antidepressant,et al.In the modern study,the extract of Bupleuri radix mainly includes a variety of chemical components such as Bupleuri radix saponin,flavonoids and volatile oil.By reviewing the relevant literature at home and abroad,this paper summarizes the research progress on the chemical composition and pharmacological effects of Bupleuri radix,and points out the future research direction to provide a certain reference basis for the subsequent research.

Vanin-1 is highly expressed in many organs such as liver, intestine, and kidney. Its main function is mainly related to the activity of pantoyl enzyme mercaptoethylamine. Several studies have shown that Vanin-1 is related to oxidative stress and inflammatory response under physiological conditions, and its role in pathological conditions depends on the diseased organ. This article summarizes the structure, properties, functions of Vanin-1 and its role in the field of kidney disease.

Objective To explore the relationship between the level of plasma ADAMTS4 and the vulnerability of carotid atherosclerotic plaque in patients with carotid artery stenosis and the clinical value of evaluating the vulnerability of the carotid atherosclerotic plaque.Methods 60 patients with carotid artery stenosis were divided into stable plaque group and vulnerable plaque group according to the histopathological typing after carotid endarterectomy (CEA).30 patients who had atherosclerosis but no carotid plaque formation served as control.Using ELISA to measure the level of plasma ADAMTS4.Results The level of plasma ADAMTS4 was significantly higher in the vulnerable-plaque group (112.74 ± 17.47) ng/ml compared with the stable plaque group (56.67 ± 22.14)ng/ml and the control group (56.67 ± 22.14)ng/ ml,P ＜ 0.001.Logistic analysis showed that high level of plasma ADAMTS4 was risk factor for vulnerability of carotid atherosclerotic plaque (P ＜ 0.05,OR =8.240,95 ％ CI:1.512-22.915).ROC curve showed that ADAMTS4 =100.935 ng/ml could accurately predict significant vulnerability with accuracy of 94.3％.Conclusion ADAMTS4 is an effective,sensitive and non-invasive biomarker to evaluate the vulnerability of carotid atherosclerotic plaque.

Objective To study the correlation between the polymorphisms of NR3C1 gene and aggressive behavior in Yunnan Han population.Methods Five SNPs of the NR3C1 gene (rs6190,rs6191,rs6198,rs41423247 and rs56149945) were genotyped in 194 unrelated prisoners who committed violent-crimes and 301 healthy controls using improved Multiplex-ligase-detection reaction(iMLDR) method,and the data were statistically analyzed with the SPSS19.0soflware and PHASE2.1platform.Results Single locus analysis showed that the allelic distribution of rs6191and rs41423247did not show significant differencesbetween the control groupand the aggressive-behavior group as well as the robbery sub-group and intentional injury sub-group.However,significant difference was foundin the rs41423247 genotype distribution betweencontrol groupand robbery sub-group (p=0.048).In addition,there were no significant differences for the four haplotypes between the control group,the attack group,the robbery subgroup and the intentional injury subgroup.Conclusion These findings indicate that rs41423247 polymorphism of the NR3C1gene might play a role in susceptibility to aggressive behavior and rs6191 polymorphismmay not be correlated withaggressive behavior.

Objective To evaluate the effect of motivational interviewing (MI) on the quality of life and self-behaviour in peritoneal dialysis patients with poor control of volume management. Methods Totally 41 peritoneal inpatients with poor control of volume management were selected as the research object and were randomly divided into two groups. The patients in the control group received routine diabetes education, while the patients in the experimental group received intervention of motivational interviewing. The patients′ Brain Natriuretic Peptide (BNP), cardiothoracic ratio (CTR), systolic blood pressure (SBP), diastolic blood pressure (DBP), self-management score and quality of life were measured before intervention and 6 months after intervention.Results The CTR and SBP level after 6 months were lower than baseline(P<0.05). The improvement of self-management and quality of life was much more significant in experimental group(P<0.05). Conclusions Motivational interviewing is more effective than routine peritoneal education on the improvement of self-management and quality of life in peritoneal dialysis patients with poor control of volume management.