Objective To investigate the feasibility of a novel molecular probe 99Tcm-3P4-RGD2 in evaluating arterial plaque stability after atorvastatin intervention in rabbits with SPECT/CT. Methods Eighteen male New Zealand rabbits were randomly divided into group A (stable plaque), group B (vulnerable plaque), and group C (vulnerable plaque with statin intervention). All rabbits were fed with high-fat food for 12 weeks. After high-fat feeding for two weeks, sham surgery was performed on group A. In the meantime, abdominal aorta injury was performed on group B and group C. After that, rabbits of group C were given oral atorvastatin (2.5 mg·kg-1·d-1). 99Tcm-3P4-RGD2 SPECT/CT imaging was performed on each group at the end of 4, 8 and 12 weeks. T/NT ratios were calculated. Animals were sacrificed at the end of 12 week after imaging studies. The abdominal aortas were collected, imaged with SPECT/CT, and evaluated by pathological HE staining and immunohistochemical analysis. MVD was calculated. Differences among 3 groups were analyzed using one-way analysis of variance. Results There was no significant radioactive uptake in the abdominal aortas of three groups on the 4th week′s imaging. The radioactive uptake in abdominal aortas increased slightly on the 8th week, with the highest radioactive uptake in group B. The radioactivity in abdominal aortas of the 3 groups maintained increasing on the 12th week, with T/NT ratios of 1.579±0.217, 1.873±0.226 and 1.524±0.237, respectively (F=8.984, P<0.05). In ex vivo abdominal aorta images, especially images of group B, radioactivity in lesion sites was higher than that in normal tissue. Accordingly, results of HE staining showed that artery plaques of group A and group C were grade Ⅱ and group B was grade Ⅳ. The MVD of group A, B and C was 8.17±1.17, 15.86±1.07 and 7.17±1.60, respectively (F=9036, P<0.05). Conclusion 99Tcm-3P4-RGD2 SPECT/CT imaging has a high sensitivity in the evaluation of arterial plaque stability after statin intervention in rabbits.

Objective:To explore the core targets and potential molecular mechanisms of tetramethylpyrazine in the treatment of rats with acute necrotizing pancreatitis (ANP) based on network pharmacology.Methods:The related co-targets of tetramethylpyrazine and ANP were screened out by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and human disease information-related databases (CTD, DisGeNET, GeneCards, OMIM); Uniprot data were used to co-link and put into the STRING database to build protein-protein interaction (PPI) networks; the Cytoscape software was used for further analysis and the key targets were obtained by using the cytoHubba plug-in. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these key targets, and finally the molecular docking models were constructed by using PyMol and AutoDockTools software. 30 male SD rats were randomly divided into the control group, ANP group, and tetramethylpyrazine treatment group (tetramethylpyrazine group). ANP rats were induced by retrograde infusion of 4% sodium taurocholate into the biliary-pancreatic duct, and the tetramethylpyrazine group rats were injected with 10 ml/kg tetramethylpyrazine through the abdominal cavity after ANP was induced. After 12 h, pancreatic tissue was taken, a pathological examination was performed routinely, and immunohistochemical staining was performed to observe the protein expression of key targets in pancreatic tissue. Blood was taken from orbits, and then the serum IL-6 and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA).Results:The drug platform screened 137 tetramethylpyrazine action targets, and the disease database screened out 513 ANP-related targets; then 25 targets were obtained through intersection, finally resulting in a total of 5 key targets: albumin (ALB), epidermal growth factor receptor (EGFR), caspase 3 (CASP3), mitogen-activated protein kinase 1 (MAPK1) and B-cell lymphoma-2-like protein 1 (BCL2L1). GO functional enrichment analysis of biological processes mainly involved reproductive structure or system development, response to antibiotics, chemical stress and reactive oxygen species, and the cellular components were mainly vesicle lumen, membrane raft, membrane microdomain, and secretory granule lumen; molecular functions mainly included SH2 domain, phosphotyrosine residue, protease binding, protein tyrosine kinase and nuclear receptor activity; KEGG pathway enrichment analysis were mainly enriched in Ras signaling pathway, PI3K-Akt signaling pathway, platinum drug resistance, phospholipase D signaling pathway, and EGFR tyrosine kinase inhibitor resistance. The average binding energy of the 5 key targets molecule docking was -4.20 kcal/mol. After hematoxylin-eosin staining, it could be seen that the gland structure of rats in the ANP group was disordered, the interlobular space was significantly increased, and neutrophil infiltration was observed in the acinar, perivascular and gland space. The pancreatic lobule space of tetramethylpyrazine group rats was slightly increased, with mild neutrophil infiltration. The protein expressions of EGFR, CASP3 and MAPK1 in the ANP group were significantly higher compared with those in the control group, and EGFR, CASP3 and MAPK1 expression in tetramethylpyrazine group was significantly lower than those in ANP group ( P<0.01); the protein expression of BCL2L1 in the ANP group were significantly higher than that in control group, and the protein expression of BCL2L1 in tetramethylpyrazine group were significantly higher than that in ANP group (all P value <0.05). The serum levels of IL-6 and TNF-α in the ANP group were significantly higher than those in the control group, and IL-6 and TNF-α in tetramethylpyrazine group were significantly lower than those in the ANP group (all P value <0.01). Conclusions:Tetramethylpyrazine could reduce the inflammatory response and oxidative stress injury after ANP by activating a variety of signaling pathways, enhancing the expression of anti-apoptotic genes, and blocking the enzymatic cascade reaction of apoptotic caspase, thus playing a protective role in pancreatic tissues of rats with ANP.

Clinical data were retrospectively reviewed for one case of penicillium marneffei infection after renal transplantation (RT) to explore a proper management of peniciliosis marneffei (PSM)transplantation.This case had a history of pulmonary tuberculosis and underwent RT due to uremia.After discharging, postoperative recovery was excellent.Recurrent cough occurred at Month 7 post-operation.Fiberoptic bronchoscopy and pulmonary CT indicated a possibility of pulmonary tuberculosis.However, a definite diagnosis of PSM was confirmed by next generation sequencing (NGS) and pathogenic bacteria culture of alveolar lavage fluid.After adjusting immunosuppressive agents and regular antifungal treatment with voriconazole, respiratory symptoms improved and pulmonary CT hinted at a resorption of lesion.Features of pulmonary CT and bronchoscopic examination were nearly similar to those of tuberculosis.Thus early bacterium culture and NGS may aid an definite diagnosis.Voriconazole is an effective treatment of the disease.

Indole-3-carbinol(I3C),an important anticancer compound found in broccoli,has attracted considerable attention.The rapid extraction and accurate analysis of I3C in the pharmaceutical industry in broccoli is challenging as I3C is unstable at low pH and high temperature.In this study,a rapid,accurate,and low-cost ultrasound-assisted dispersive-filter extraction(UADFE)technique based on poly(deep eutectic solvent)-graphene oxide(PDES-GO)adsorbent was developed for the isolation and analysis of I3C in broccoli for the first time.PDES-GO with multiple adsorption interactions and a fast mass transfer rate was synthesized to accelerate adsorption and desorption.UADFE was developed by combining dispersive solid-phase extraction(DSPE)and filter solid-phase extraction(FSPE)to realize rapid extraction and separation.Based on the above two strategies,the proposed PDES-GO-UADFE method coupled with high-performance liquid chromatography(HPLC)allowed the rapid(15-16 min),accurate(84.3％-96.4％),and low-cost(adsorbent:3.00 mg)analysis of I3C in broccoli and was superior to solid-phase extraction,DSPE,and FSPE methods.The proposed method showed remarkable linearity(r=0.9998;range:0.0840-48.0 μg/g),low limit of quantification(0.0840 μg/g),and high precision(relative standard deviation≤5.6％).Therefore,the PDES-GO-UADFE-HPLC method shows significant potential in the field of pharmaceutical analysis for the separation and analysis of anti-cancer compounds in complex plant samples.