Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Elderly patients are a crucial population for medical treatment and referral.The establishment of standardized and efficient referral channels is essential for enhancing the referral process, improving treatment outcomes for the elderly, and optimizing the allocation of medical resources.Referral network analysis examines the integrity, structure, and dynamics of referrals to infer the characteristics of the network.This can offer insights for enhancing referral policies and elevating medical service standards.While existing research predominantly concentrates on referral networks within the general population, there is a noticeable gap in studies focusing on elderly patients.This review article assesses domestic and international research on networks formed between medical institutions or physicians through patient referrals, aiming to inform and enhance referral policies in our country.

Objective: To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation. Methods: Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot. Results: A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05). Conclusion MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Objective:To analyze the effects of different psychological interventions on cancer patients' fear of cancer recurrence(FCR).Methods:Randomized controlled trials examining the effects of various psychological interventions on FCR among cancer patients were searched for in both Chinese and English literature databases.A network meta-analysis was conducted to explore the intervention effects,utilizing standardized mean difference(SMD),95％confidence interval(CI),and surface under the cumulative ranking(SUCRA)of FCR as the effect indicators.Results:A total of 34 studies involving 3 772 participants were included,of which five types of psycho-logical interventions were evaluated,namely acceptance and commitment therapy(ACT),gratitude-expansion thera-py(GET),cognitive behavioral therapy(CBT),mindfulness therapy(MT),and multi-component psychological in-tervention(Mul).According to the time of effect evaluation,three effect evaluation timing were confirmed,with immediate post-intervention group,1-2 months post-intervention group,and 3-6 months post-intervention group identified.Compared with conventional care,in the immediate post-intervention group,ACT(SMD=-1.80,95％CI:-2.47--1.13),GET(SMD=-1.33,95％CI:-2.07--0.59),MT(SMD=-0.59,95％CI:-1.03--0.14)and CBT(SMD=-0.54,95％CI:-0.93--0.15)could effectively reduce FCR,and the SUCRA val-ue of ACT was upmost to 0.96.In the 1-2 months post-intervention group,GET(SMD=-2.32,95％CI:-2.99--1.65)and ACT(SMD=-1.46,95％CI:-2.23--0.70)could effectively reduce FCR,and the SUCRA value of GET was upmost to 0.99.In the 3-6 months post-intervention group,Mul(SMD=-1.82,95％CI:-3.03--0.61)and MT(SMD=-1.43,95％CI:-2.33--0.54)could effectively reduce FCR,and the SU-CRA value of Mul was upmost to 0.90.Conclusion:Different psychological interventions vary in their effectiveness on FCR across effect evaluation time points,highlighting the need for tailored approaches on mitigating FCR in clin-ical practice.

In order to explore the potential of nanoparticles from ethanol extracts of Euphorbia he-lioscopia L.(ZQNPs)in antibacterial application.In this study,ZQNPs were prepared by the self-assembly method using alcohol extract of Euphorbia helioscopia L.,polylysine and polyethylene glycol 1 000 as raw materials.The morphology and structure of ZQNPs were characterized by transmission electron microscopy,UV-vis spectrophotometer,and Fourier transform infrared spec-troscopy.The growth and biofilm inhibition of ZQNPs against methicillin-resistant Staphylococcus aureus(MRSA)were tested by broth microdilution,crystal violet,and checkerboard assays.The broad-spectrum antibacterial activity and antibacterial activity of ZQNPs against three clinical strains were evaluated by broth microdilution method.Finally,the antibacterial mechanism of ZQNPs was preliminarily explored by morphological observation and soluble protein detection of MRSA.The results showed that ZQNPs were self-assembled and cross-linked multi-faceted spheres with an average diameter of 67 nm.The MIC of ZQNPs against MRSA was 8 mg/L,and the antibacterial effect was much better than that of Euphorbia helioscopia L.mongolicum alcohol extract(MIC＞32 mg/L).The time killing curve again showed that ZQNPS had a good antibacteri-al effect on MRSA(8 mg/L)biofilm inhibition rate of 89％,and the antibacterial effect of ZQNPS combined with cefquinome sulfate showed additive results.The mics of ZQNPs against Gram-posi-tive bacteria(S.aureus)and gram-negative bacteria(E.coli)were 16 mg/L and 8 mg/L,respec-tively.The mics of ZQNPS against E.coli clinical strains were stable between 8 and 16 mg/L.The MIC of Salmonella clinical strains was 32-64 mg/L,and the MIC of S.aureus clinical strains was 8-64 mg/L.Preliminary antibacterial mechanism showed that ZQNPs could destroy the membrane structure of MRSA,lead to the release of intracellular substances,and affect the growth of MRSA.These results indicate that ZQNPs have a good antibacterial effect and have potential application value in antimicrobial therapy.

In order to explore the potential of nanoparticles from ethanol extracts of Euphorbia he-lioscopia L.(ZQNPs)in antibacterial application.In this study,ZQNPs were prepared by the self-assembly method using alcohol extract of Euphorbia helioscopia L.,polylysine and polyethylene glycol 1 000 as raw materials.The morphology and structure of ZQNPs were characterized by transmission electron microscopy,UV-vis spectrophotometer,and Fourier transform infrared spec-troscopy.The growth and biofilm inhibition of ZQNPs against methicillin-resistant Staphylococcus aureus(MRSA)were tested by broth microdilution,crystal violet,and checkerboard assays.The broad-spectrum antibacterial activity and antibacterial activity of ZQNPs against three clinical strains were evaluated by broth microdilution method.Finally,the antibacterial mechanism of ZQNPs was preliminarily explored by morphological observation and soluble protein detection of MRSA.The results showed that ZQNPs were self-assembled and cross-linked multi-faceted spheres with an average diameter of 67 nm.The MIC of ZQNPs against MRSA was 8 mg/L,and the antibacterial effect was much better than that of Euphorbia helioscopia L.mongolicum alcohol extract(MIC＞32 mg/L).The time killing curve again showed that ZQNPS had a good antibacteri-al effect on MRSA(8 mg/L)biofilm inhibition rate of 89％,and the antibacterial effect of ZQNPS combined with cefquinome sulfate showed additive results.The mics of ZQNPs against Gram-posi-tive bacteria(S.aureus)and gram-negative bacteria(E.coli)were 16 mg/L and 8 mg/L,respec-tively.The mics of ZQNPS against E.coli clinical strains were stable between 8 and 16 mg/L.The MIC of Salmonella clinical strains was 32-64 mg/L,and the MIC of S.aureus clinical strains was 8-64 mg/L.Preliminary antibacterial mechanism showed that ZQNPs could destroy the membrane structure of MRSA,lead to the release of intracellular substances,and affect the growth of MRSA.These results indicate that ZQNPs have a good antibacterial effect and have potential application value in antimicrobial therapy.

Objective:To analyze the effects of different psychological interventions on cancer patients' fear of cancer recurrence(FCR).Methods:Randomized controlled trials examining the effects of various psychological interventions on FCR among cancer patients were searched for in both Chinese and English literature databases.A network meta-analysis was conducted to explore the intervention effects,utilizing standardized mean difference(SMD),95％confidence interval(CI),and surface under the cumulative ranking(SUCRA)of FCR as the effect indicators.Results:A total of 34 studies involving 3 772 participants were included,of which five types of psycho-logical interventions were evaluated,namely acceptance and commitment therapy(ACT),gratitude-expansion thera-py(GET),cognitive behavioral therapy(CBT),mindfulness therapy(MT),and multi-component psychological in-tervention(Mul).According to the time of effect evaluation,three effect evaluation timing were confirmed,with immediate post-intervention group,1-2 months post-intervention group,and 3-6 months post-intervention group identified.Compared with conventional care,in the immediate post-intervention group,ACT(SMD=-1.80,95％CI:-2.47--1.13),GET(SMD=-1.33,95％CI:-2.07--0.59),MT(SMD=-0.59,95％CI:-1.03--0.14)and CBT(SMD=-0.54,95％CI:-0.93--0.15)could effectively reduce FCR,and the SUCRA val-ue of ACT was upmost to 0.96.In the 1-2 months post-intervention group,GET(SMD=-2.32,95％CI:-2.99--1.65)and ACT(SMD=-1.46,95％CI:-2.23--0.70)could effectively reduce FCR,and the SUCRA value of GET was upmost to 0.99.In the 3-6 months post-intervention group,Mul(SMD=-1.82,95％CI:-3.03--0.61)and MT(SMD=-1.43,95％CI:-2.33--0.54)could effectively reduce FCR,and the SU-CRA value of Mul was upmost to 0.90.Conclusion:Different psychological interventions vary in their effectiveness on FCR across effect evaluation time points,highlighting the need for tailored approaches on mitigating FCR in clin-ical practice.