Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.

Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.

Objective Comprehensively analyzing the epilepsy-related genes by bioinformatics methods,and to explore their functions based on network and pathway analysis.Methods I Collected epilepsy-related genes through OMIM,DisGeNET,GeneCards databases and literatures deposited in PUBMED.Performed gene ontology(GO)and pathway enrichment analysis using"ClusterProfiler"R package,and the correlation between pathways was identified through pathway crosstalk analysis.Epilepsy-related genes were then mapped to human protein-protein interaction network(PPIN)to obtain epilepsy-specific PPIN,and extracted the hub and potential genes based on network topology.Results A total of 572 epilepsy-related genes were collected,642 significant GO biological process items and 80 Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways,including learning,memory and cognition,were obtained by enrichment analysis.Based on PPIN analysis,10 hub genes of the epilepsy were extracted and most of them are gamma-aminobutyric acid(GABA)receptor genes.By integrating PPIN and WGCNA analysis,17 potential genes were extracted,involving heat shock protein,growth factor receptor binding protein,etc.Conclusion Epilepsy is a complex process,involving the abnormality of multiple functional genes,multiple biological processes and pathways are closely contact through multiple functional genes,and collectively lead to the occurrence of epilepsy.

OBJECTIVETo observe the level of intracellular reactive oxygen species (ROS) in rats with severe burn and pulmonary microvascular endothelial cells (PMVECs) treated with serum of rat with burn injury, and to investigate the relationship between ROS and apoptosis of PMVECs.

METHODS(1) Twenty-four SD rats were divided into sham injury group ( n = 3) and burn group (n = 21) according to the random number table (the same grouping method below). Rats in burn group were inflicted with 30% TBSA full-thickness scald on the back, and rats in sham injury group were sham injured. Blood samples were collected from abdominal aorta at post injury hour 6, 12, 24, 36, 48, 60, 72 respectively from 3 rats of burn group. The serum content of ROS was assayed by ELISA. The same determination was performed in rats of sham injury group. (2) Five rats were subjected to scald injury as above, and burn serum was prepared 24 hours after injury. Another 5 rats without receiving any treatment were used to prepare normal serum. (3) Marginal pulmonary tissue was harvested from 20 SD young rats. Cells were cultured with tissue block method and indentified with immunohistochemical staining. The third passage of PMVECs in logarithmic phase were inoculated in 6-well plates and 12-well plates. PMVECs in both plates were divided into 4 groups: normal serum group, burn serum group, normal serum + MnTBAP group, and burn serum + MnTBAP group, with 3 wells in each group. Cells in the former 2 groups were respectively cultured with special nutrient solution of endothelial cells without serum added with 15% healthy rat serum or 15% burn rat serum. Cells in the latter 2 groups were cultured with the same culture conditions as in the former two groups correspondingly with addition of 100 µmol/L MnTBAP in the nutrient solution. After being cultured for 24 h, the content of ROS in PMVECs in 6-well plates was detected with flow cytometry. The apoptosis of PMVECs in 12-well plates was observed with acridine orange-ethidium bromide staining, and the apoptosis rate was calculated. Data were processed with one-way analysis of variance and LSD-t test.

RESULTS(1) The serum contents of ROS in rats of burn group were respectively (187 ± 21), (235 ± 22), (231 ± 25), (291 ± 20), (315 ±23) nmol/mL at post injury hour 24, 36, 48, 60, 72, which were significantly higher than that in sham injury group [(141 ± 19) nmol/mL, with t values respectively 7. 86, 9. 57, 13. 87, 14.98, 18.40, P values below 0.01]. (2) Primary cells grew slowly and showed a cobblestone appearance. After passages, cells grew with orderly distribution. The positive rate of coagulation factor VIII of cells was (96 ± 5)% , and thus they were identified as PMVECs. (3) In normal serum group, burn serum group, normal serum + MnTBAP group, and burn serum + MnTBAP group, the contents of ROS in PMVECs were respectively 798 ± 40, 1 294 ± 84, 763 ± 59, 926 ± 42 ( F =93.01, P <0.01), and the apoptosis rates of PMVECs were respectively (6.2 ± 1.3)%, (57.3 ± 6. 7)%, (3.7 ± 0. 8)%, (28.7 ± 5. 7)% (F = 224.50, P <0.01) after being cultured for 24 h. Compared with those of normal serum group, the content of ROS and apoptosis rate of PMVECs in burn serum group increased significantly (with t values respectively 10.40 and 49.06, P values below 0.01). The content of ROS and apoptosis rate of PMVECs in burn serum + MnTBAP group were significantly lower than those in burn serum group (with t values respectively 7.48 and 23.94, P values below 0.01).

CONCLUSIONSSerum content of ROS was increased in severely burned rats. Burn rat serum stimulation on PMVECs can lead to the increase of the intracellular ROS and induce apoptosis. However application of MnTBAP can scavenge ROS and reduce the apoptosis induced by burn rat serum.

Animals ; Apoptosis ; Burns ; blood ; therapy ; Endothelial Cells ; pathology ; Enzyme-Linked Immunosorbent Assay ; Lung ; blood supply ; Oxygen ; Rats ; Reactive Oxygen Species ; blood ; Serum ; metabolism