Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

In recent years,studies have shown that C/EBP β plays an important role in the occurrence and development of liver cancer,but its specific molecular regulatory mechanism is still unclear.In this study,we analyzed the GEO database and the Kaplan-Meier Plotter database and found that the mRNA expression of C/EBP β was low in hepatocellular carcinoma(HCC)cells(P＜0.05),and its low ex-pression was closely related to the prognosis of HCC patients.Furthermore,functional enrichment analy-sis and TIMER database analysis showed that C/EBP β was mainly involved in biological processes such as cell cycle and DNA transcription,and the expression level of C/EBP β had a strong correlation with the immune infiltration of CD4+T cells and macrophages(P＜0.05).To further investigate the effect of C/EBP β on the proliferation and migration of HCC cells.In the experiment,HCC cells were transiently transfected with C/EBP β siRNA and divided into si-NC group and siC/EBP β group.The mRNA and protein levels of C/EBP β in HCC cells were significantly reduced by qRT-PCR and Western blot(P＜0.05),and MTT detection,plate cloning assay,and 5-ethynyl-2'deoxyuracil nucleoside(Edu)assay confirmed that knockdown of C/EBP β promotes the proliferation of HCC cells(P＜0.05);Transwell and scratch assays confirmed that knockdown of C/EBP β promote the migration of HCC cells;Western blot method was used to detect the effect of knockdown of C/EBP β on the expression of migration-related proteins(E-cadherin,N-cadherin)and Wnt/β-catenin signaling pathway proteins.The results showed that knockdown of C/EBP β promotes epithelial-mesenchymal transition(EMT)and activates gene ex-pression of Wnt/β-catenin signaling pathway in HCC cells(P＜0.05).In conclusion,C/EBP β was un-derexpressed in HCC tissues and was positively correlated with the survival prognosis of patients.Knock-down of C/EBP β may promote the proliferation,migration,and epithelial-mesenchymal transformation of HCC cells by activating the Wnt/β-catenin signaling pathway,which provides a basis for the role of C/EBP β in the occurrence and development of HCC and may be a potential target in the diagnosis and treatment of HCC.

Objective:To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism.Methods:Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group(untreated NB4 cells),shikonin group(0.3 μmol/L shikonin treatment),740Y-P group(15 μmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment),shikonin+740Y-P group(0.3 μmol/L shikonin and 15 μmol/L 740Y-P co-treatment),after 24 hours of treatment,the cells were used for subsequent experiments.CCK-8 method was used to detect cell viability,monodansylcadaverine(MDC)staining to detect the aggregation of autophagic vesicles,flow cytometry to detect cell apoptosis,and Western blot to detect the expression of Beclinl,LC3,p62,Bax,cleaved caspase-3,Bcl-2 and PI3K/Akt/mTOR pathway related proteins.Results:Compared with the control group,the purple punctate fluorescence intensity,apoptosis rate,Beclinl,LC3-Ⅱ/LC3-Ⅰ,cleaved caspase-3,and Bax protein expression in NB4 cells were increased in the shikonin group,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were decreased(all P＜0.05).Compared with the control group,the purple punctate fluorescence intensity,apoptosis rate,Beclin1,LC3-Ⅱ/LC3-1,cleaved caspase-3,and Bax protein expression in NB4 cells were decreased,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group(all P＜0.05).Compared with the shikonin group,the purple punctate fluorescence intensity,apoptosis rate,Beclinl,LC3-Ⅱ/LC3-1,cleaved caspase-3,and Bax protein expression in NB4 cells were decreased,while OD450 value(24,48 h)and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group(all P＜0.05).Compared with the control group,the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K,p-Akt,and p-mTOR in NB4 cells were significantly decreased in the shikonin group,while those in the 740Y-P group were increased(all P＜0.05).Compared with the shikonin group,the expressions of p-PI3K,p-Akt,and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group(all P＜0.05).Conclusion:Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Objective:To investigate the clinical efficacy of ibrutinib combined with venetoclax in the treatment of relapsed/refractory diffuse large B-cell lymphoma(R/R DLBCL),and to analyze the factors affecting efficacy and prognosis.Methods:Clinical data of 62 R/R DLBCL patients admitted to our hospital from August 2017 to July 2022 were retrospectively analyzed.All patients were treated with ibrutinib combined with venetoclax.The clinical efficacy and drug safety were evaluated.The effects of clinical features on short-term efficacy and overall survival(OS)were analyzed.Results:The objective response rate(ORR)of 62 patients was 48.39％.The extranodal lesions,intermediate-high/high risk of NCCN-IPI,intermediate-high/high risk of IPI,progression or recurrence time＜12 months were the risk factors affecting the short-term efficacy of chemotherapy in R/R DLBCL patients(all P＜0.05).The most common adverse effect was neutropenia(75.19％),and the incidence of grade Ⅱ-Ⅳ neutropenia was 52.71％.The l-year and 2-year OS rates of 62 patients were 48.51％and 31.56％,respectively,and the median OS time was 12 months.Multivariate analysis showed that objective remission after chemotherapy[HR=0.080(95％CI:0.028-0.235)]was a protective factor for OS in R/R DLBCL patients,and intermediate-high/high risk of NCCN-IPI[HR=4.828(95％CI:1.546-15.080)]was an independent risk factor affecting the prognosis of R/R DLBCL patients.Conclusion:Ibrutinib combined with venetoclax can be used as an effective treatment regimen for R/R DLBCL,and NCCN-IPI can be used as a prognostic indicator.Objective remission after chemotherapy is beneficial for R/R DLBCL patients to achieve better OS.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.