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.

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Objective To investigate the effect of short-term complications after D2 radical gastrectomy on long-term survival rate of gastric cancer patients. Methods A retrospective case-control study was conducted on 421 patients with gastric cancer who underwent D2 radical gastrectomy. According to the short-term postoperative complications, they were divided into experimental group (complication group, n=76) and control group (without complication group, n=345). In order to reduce the selection bias, the long-term survival rate of the two groups was tested by Kaplan-Meier survival analysis method after balancing the variables by propensity score matching (PSM). Log rank method was used for univariate analysis and Cox multivariate analysis was used for prognostic factors. Results There was no significant difference in long-term survival rate between the experimental group and the control group (P > 0.05). Histological type, lymph node metastasis rate and pTNM stage were independent risk factors for long-term survival. Conclusion The short-term complications after D2 radical gastrectomy have no significant impact on the long-term survival rate of gastric cancer patients, but it has certain clinical significance to actively prevent and control complications.

Objective To compare the effect and safety of stenting versus directional atherectomy (DA) in the treatment of TASCⅡ A and B superficial femoral artery lesions.Methods 100 patients with TASC Ⅱ A and B lesions were divided into percutaneous transluminal stenting(PTS) group (n =50) and DA group (n =50).Patients were compared in terms of technical success rate,treatment success rate,first operation cost,postoperative ankle brachial index (ABI),limb salvage rate,survival,and patency.Results The technical success rate in both PTS and DA group was 100％.The treatment success rate was 98％ vs.86％,P＞0.05.Postoperative ABI:0.82 ±0.19 vs.0.80 ±0.27,P＞0.05.First operation cost:(34 820 ± 1 051) yuan vs.(45 635 ± 1 358) yuan,P ＜0.001;All patients were followed-up for up to 2-year,the cumulative patency rate was 81.6％ vs.72.9％ (P＞0.05).Limb salvage rate was 97.9％ vs.93.8 ％,P ＞ 0.05.Conclusion There were no significant differences in the effect and safety of PTS versus DA in the treatment of TASCⅡ A and B superficial femoral artery lesions.

Objective To investigate methods and results of endovascular treatment in TASC (Ⅱ) D-type femoral artery occlusion. Methods From January 2012 to May 2013, 26 cases (26 branches) of superficial femoral artery occlusion with endovascular treatment of TASC (Ⅱ) D-type superficial femoral artery occlusion were retrospectively reviewed. The effi-cacy was evaluated through ABI, CTA, DSA and symptoms improved. Results 26 branches were treated with endovascular methods. Technical success rate was 80.7%(21/26), including 13 branche with stent implantation, 6 branches with Silver-hawk atherectomy and 2 branches with Viabahn stent implantation. All patients were followed up for a mean period of (10.3 ± 1.2)months, primary patency rates at 6 months were 69.2%in stent group, 66.7%in Silverhawk atherectomy group and 100%in Viabahn stent group. Conclusion Endovascular treatment of TASC (Ⅱ) D-type femoral artery occlusion can lead to satisfactory short term patency rates, and Viabahn stent is the latest treatment.

OBJECTIVE: To study the effects of Tongbi Mixture 2, a compound traditional Chinese herbal medicine for treating rheumatoid arthritis (RA), on immunoregulation of T lymphocytes in rats with collagen-induced arthritis (CIA). METHODS: Forty Wistar rats were randomly divided into normal control group, untreated group, Tongbi Mixture 2-treated group, methotrexate (MTX)-treated group and Tripterygium wilfordii polyglycoside (TWP)-treated group. Except for the rats of the normal control group (injection with normal saline), rats of the other four groups were subcutaneouly multipoint-injected with collagen protein II to induce CIA. The rats were treated with normal saline, Tongbi Mixture 2, MTX tablets and TWP tablets respectively for 36 days. The expressions of CD28 and CD152 were detected by flow cytometry, while the content of tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme-linked immunosorbent assay. RESULTS: The expression of CD28 among the three drug treated groups had no statistical difference (P>0.05), while significantly higher than that of the normal control group (P<0.01) and lower than that of the untreated group (P<0.01). The expression of CD152 in the Tongbi Mixture 2 treated-group was lower than those of the MTX- and TWP-treated groups (P<0.05, P<0.01), but had no statistical difference as compared with the normal control group (P>0.05). There were no statistical differences in content of TNF-alpha between the drug treated groups and the normal control group (P>0.05), but the content of TNF-alpha of the drug treated groups was lower than that of the untreated group (P<0.05 or P<0.01). CONCLUSION: Tongbi Mixture 2 can inhibit T lymphocytes through down-regulating the expressions of CD28 and CD152 and the content of TNF-alpha, which may be the major mechanisms in treating RA.

Recombinant human interleukin-1 receptor antagonist was expressed in E. coli as an insoluble inclusion body. The inclusion body was dissolved in the 8 M urea and then the solution was diluted untill the concentration of urea became 2 M. By ion exchange chromatography the protein in the solution of 2 M urea was refolded and purified. At last the purity of product is more than 95% and its bioactivity is more than 1 x 10(5) IU/mg while it has little endotoxin. Western-Blotting also indicates that recombinant protein can react with antibodies against anti-hIL-1ra.
Escherichia coli ; genetics ; metabolism ; Humans ; Inclusion Bodies ; metabolism ; Interleukin 1 Receptor Antagonist Protein ; biosynthesis ; genetics ; Protein Folding ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification

OBJECTIVETo investigate the diagnosis and treatment of incidental prostate cancer (IPC) following transurethral plasma kinetic vaporization prostatectomy (TUPVP).

METHODSPathological examinations were conducted on 134 benign prostate hyperplasia specimens by means of series microtomy after TUPVP.

RESULTSFifteen cases of IPC were detected from the total number of TUPVP specimens, with a pick-up rate of 11.2%. Dual testicle resection with endocrine therapy was performed in 4 cases of Stage A2 patients, and endocrine therapy alone was conducted in 9 cases of Stage A1 patients. Thirteen patients were followed up for 7 to 15 months and all lived without cancer (PSA 0.15 - 4.0 microg/L).

CONCLUSIONTUPVP and series microtomy may be helpful to the diagnosis of IPC. Patients at Stage A1 need mere endocrine therapy, while those at Stage A2 warrant dual testicle resection.

Aged ; Aged, 80 and over ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Orchiectomy ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; pathology ; surgery ; Prostatic Neoplasms ; pathology ; surgery ; Transurethral Resection of Prostate