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.

Objective To investigate the value of fragmented QRS complex(fQRS)in the electro-cardiogram,heart rate variability(HRV)and LVEF in evaluating the prognosis in patients with dilated cardiomyopathy(DCM).Methods A retrospective analysis was conducted on 59 DCM pa-tients admitted in the Second Affiliated Hospital of Wannan Medical College from January 2020 to December 2023.According to the occurrence of MACE during 6-month follow-up period,they were classified into a poor prognosis group(26 cases)and a good prognosis group(33 cases).Clin-ical baseline data,positive rate of fQRS,HRV and LVEF were compared between the two groups.Time-domain measurements of HRV included standard deviation of normal NN intervals(SDNN),standard deviation of the averages of NN intervals in all 5 min segments of the entire recording(SDANN),mean of the standard deviation of NN intervals for all 5 min segments of the entire recording(SDNN index),root mean square of standard deviation of NN intervals(r-MSSD)and HRV triangular index.Spearman/Pearson correlation analysis was performed to analyze the correlation of prognosis of DCM with positive rate of fQRS,HRV and LVEF.ROC curve was drawn to analyze the efficiency of fQRS,HRV and LVEF in predicting the prognosis of DCM.Results The poor prognosis group exhibited significantly higher positive rate of fQRS and obvi-ously reduced SDNN,SDANN,SDNN index,r-MSSD,triangular index and LVEF when compared with the good prognosis group(P＜0.01).Correlation analysis suggested that poor prognosis of DCM was positively correlated with the positive rate of fQRS(P＜0.01),and negatively with SDNN,SDANN,SDNN index,r-MSSD,triangular index and LVEF(P＜0.05,P＜0.01).ROC curve analysis revealed that the AUC value of above indicators in turn in predicting the prognosis of DCM was 0.718,0.7 56,0.7 62,0.807,0.858,0.805 and 0.747,respectively,and the AUC value of their combination was 0.980(P＜0.01).Conclusion fQRS,HRV and LVEF have important cor-relation with poor prognosis of DCM patients.Their combination can be used as an effective mark-er for clinical evaluation and prediction of poor prognosis of DCM.

Objective To investigate the value of fragmented QRS complex(fQRS)in the electro-cardiogram,heart rate variability(HRV)and LVEF in evaluating the prognosis in patients with dilated cardiomyopathy(DCM).Methods A retrospective analysis was conducted on 59 DCM pa-tients admitted in the Second Affiliated Hospital of Wannan Medical College from January 2020 to December 2023.According to the occurrence of MACE during 6-month follow-up period,they were classified into a poor prognosis group(26 cases)and a good prognosis group(33 cases).Clin-ical baseline data,positive rate of fQRS,HRV and LVEF were compared between the two groups.Time-domain measurements of HRV included standard deviation of normal NN intervals(SDNN),standard deviation of the averages of NN intervals in all 5 min segments of the entire recording(SDANN),mean of the standard deviation of NN intervals for all 5 min segments of the entire recording(SDNN index),root mean square of standard deviation of NN intervals(r-MSSD)and HRV triangular index.Spearman/Pearson correlation analysis was performed to analyze the correlation of prognosis of DCM with positive rate of fQRS,HRV and LVEF.ROC curve was drawn to analyze the efficiency of fQRS,HRV and LVEF in predicting the prognosis of DCM.Results The poor prognosis group exhibited significantly higher positive rate of fQRS and obvi-ously reduced SDNN,SDANN,SDNN index,r-MSSD,triangular index and LVEF when compared with the good prognosis group(P＜0.01).Correlation analysis suggested that poor prognosis of DCM was positively correlated with the positive rate of fQRS(P＜0.01),and negatively with SDNN,SDANN,SDNN index,r-MSSD,triangular index and LVEF(P＜0.05,P＜0.01).ROC curve analysis revealed that the AUC value of above indicators in turn in predicting the prognosis of DCM was 0.718,0.7 56,0.7 62,0.807,0.858,0.805 and 0.747,respectively,and the AUC value of their combination was 0.980(P＜0.01).Conclusion fQRS,HRV and LVEF have important cor-relation with poor prognosis of DCM patients.Their combination can be used as an effective mark-er for clinical evaluation and prediction of poor prognosis of DCM.

Objective:To summarize the best evidence of intracavitary electroencephalogram positioning in peripherally inserted central catheter (PICC) catheterization, and investigate the clinical application of the best evidence.Methods:The literature on the intracavitary electroencephalogram positioning technology in the head end positioning of PICC catheterization was searched through computers on websites or data bases such as Cochrane Library, Infusion Nursing Society, PubMed, ScienceDirect, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from the establishment of the database to June 30, 2022. The literature evaluation standards and evidence grading system of the Joanna Briggs Institute Evidence-Based Health Care Center Database were used for literature quality evaluation and evidence grading, summarizing the best evidence. Based on the summary of evidence, the best evidence for intracavitary electrocardiogram positioning guided PICC catheterization was applied to the survey questionnaire. From November to December 2022, a snowball sampling method was used to select 119 PICC nurses for a questionnaire survey.Results:A total of 31 articles were included, consisting of 24 randomized controlled trials, two systematic reviews, four Meta-analysis, and one group standard. We summarized 20 pieces of evidence from 7 aspects, including preoperative evaluation and preparation, catheter delivery process, guidewire connection, guided intracavitary electroencephalogram, timing of catheter withdrawal, optimal position judgment, and effect evaluation. The survey results showed that more than half of the nurses were consistent with the evidence in terms of evaluation and preparation, catheter delivery process, guided intracavitary electroencephalogram, guidewire connection, and timing of catheter withdrawal. The selection of the optimal location judgment was relatively scattered and needed further research.Conclusions:This study provides evidence-based basis for the PICC catheterization positioning using intracavitary electroencephalogram. Based on clinical practice, specialized nurses select the best evidence and develop a management plan that suits individual circumstances, which can ensure maximum patient benefits and continuously improve nursing quality.

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

In recent years, the role of inhibitor kappa B kinaseβ (IKKβ) in the process of tumorigenesis has gradually been elucidated. IKK is involved in tumor cell proliferation and survival by acting on multiple molecular pathways. Inhibition of IKKβ has been identified as a promising treatment for cancer. Researchers have developed a series of IKKβ inhibitors and found that they can effectively inhibit tumor growth, but no IKKβ inhibitors have been used clinically to treat cancer. We discuss progress in understanding the role of IKKβ in tumorigenesis and review the recent development of main inhibitors of IKKβ.

Objective:To evaluate the incidence of birth defects in offspring using frozen semen from sperm banks by meta-analysis, to provide scientific evidence for the safety and reliability of frozen semen in assisted reproductive technology (ART).Methods:China National Knowledge Infrastructure (CNKI), Wanfang Digital Database (Wanfang), VIP Citation Database (VIP), CBMDisc and PubMed were searched about birth defects using frozen semen in ART since the establishment to October 1, 2019. Literatures were screened according to the predefined inclusion and exclusion criteria and evaluated based on the STROBE statement.Results:Thirteen studies with 33 398 cases were included, the rate of birth defects using frozen semen was 1.09% (95% CI=0.85%-1.32%), lower than that published by the Chinese Ministry of Health (1.53%, P<0.001). The rate was 1.06% (95% CI=0.78%-1.35%) in artificial insemination by donor (AID), 0.60% (95% CI=0.03%-1.22%) in in vitro fertilization (IVF) and 1.35% (95% CI=0.06%-2.75% ) in intracytoplasmic sperm injection (ICSI), the difference was not statistically significant ( P=0.785). Among the birth defects, the cardiovascular system had the highest rate, followed by the central nervous system and musculoskeletal system and congenital urogenital system and so on. Conclusion:ART with cryopreserved donor sperm does not increase the risk of birth defects. However, more studies with large sample sizes are needed to confirm this conclusion because some papers with low study quality were included in this study.

Objective:To evaluate the incidence of birth defects in offspring using frozen semen from sperm banks by meta-analysis, to provide scientific evidence for the safety and reliability of frozen semen in assisted reproductive technology (ART).Methods:China National Knowledge Infrastructure (CNKI), Wanfang Digital Database (Wanfang), VIP Citation Database (VIP), CBMDisc and PubMed were searched about birth defects using frozen semen in ART since the establishment to October 1, 2019. Literatures were screened according to the predefined inclusion and exclusion criteria and evaluated based on the STROBE statement.Results:Thirteen studies with 33 398 cases were included, the rate of birth defects using frozen semen was 1.09% (95% CI=0.85%-1.32%), lower than that published by the Chinese Ministry of Health (1.53%, P<0.001). The rate was 1.06% (95% CI=0.78%-1.35%) in artificial insemination by donor (AID), 0.60% (95% CI=0.03%-1.22%) in in vitro fertilization (IVF) and 1.35% (95% CI=0.06%-2.75% ) in intracytoplasmic sperm injection (ICSI), the difference was not statistically significant ( P=0.785). Among the birth defects, the cardiovascular system had the highest rate, followed by the central nervous system and musculoskeletal system and congenital urogenital system and so on. Conclusion:ART with cryopreserved donor sperm does not increase the risk of birth defects. However, more studies with large sample sizes are needed to confirm this conclusion because some papers with low study quality were included in this study.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.
Carcinoma, Hepatocellular ; drug therapy ; Catheterization, Peripheral ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Hepatic Artery ; Humans ; Liver Neoplasms ; drug therapy ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Prognosis ; Thrombosis ; Vena Cava, Inferior

Objective To explore the shape change characteristics of Oncomelania hupensis snail shell after the snails being passively migrated into Shandong intake area of the South-to-North Water Diversion Project. Methods The snails raised on the Dushan island in Weishan Lake region were captured,and 115 the first filial generation snails and 107 the second filial generation ones were selected. The length and width of shells and apertures,and the labial ridge thickness of those snails were measured,the longitudinal rib number of snail spiral was counted,and 107 parental snails were chosen as controls. Results The labial ridge thickness of the filial generation snail was significantly reduced with the increase of algebras,and the labial ridge thickness among the 3 generations had a significant difference(P<0.01). Both the length of snail shell and the width of snail apertures were de-creased,while the width of snail shell,the length of snail apertures,the multiplication product of snail aperture’s length and width and the longitudinal rib number of snail spiral were all increased. Conclusion The body size of Oncomelania snails in Weishan Lake region becomes smaller,and their shells become thinner,which indicates that the environment of the lake region is not suitable for snail breeding,and the snails have natural decay tendency with the extension of time.