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 analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.

OBJECTIVES: To investigate the correlation of serum levels of bridging integrating factor 1 (BIN1) with acute myocardial infarction (AMI) and Killip class of the patients. METHODS: We retrospectively collected the data from 94 patients with AMI and 30 healthy individuals for analysis of the correlations of serum BIN1 levels with Killip class, TIMI scores, and neutrophil-to-lymphocyte ratio (NLR). We also assessed the diagnostic value of BIN1 combined with NLR for AMI. RESULTS: Serum BIN1 levels were significantly lower in AMI patients than in the healthy individuals (P=0.032). The AMI patients with Killip class I had significantly lower serum BIN1 levels than the healthy individuals (P=0.008). Serum BIN1 level was an independent predictor of AMI with a predictive value of 0.630 (95% CI: 0.513-0.748) at the optimal cutoff level of 0.341 ng/mL, a specificity of 50%, and a sensitivity of 78.5%. Serum BIN1 level was also an independent predictor for Killip class I group in the AMI patients with a predictive value of 0.672 (95% CI: 0.548-0.797) at the optimal cutoff level of 0.287 ng/mL, a specificity of 74.1%, and a sensitivity of 60%. For AMI diagnosis, the combination of NLR and serum BIN1 level had a predictive value of 0.811 (95% CI: 0.727-0.895) at the optimal cutoff level of 0.548 ng/mL, with a specificity of 92.6% and a sensitivity of 62.2%. There was a positive correlation between serum BIN1 level and TIMI score in AMI patients (r=0.186, P=0.003). CONCLUSIONS BIN1 is correlated with AMI and can be helpful for predicting short-term prognosis of the patients, and BIN1 combined with NLR has a high diagnostic value for AMI.
Humans ; Myocardial Infarction/diagnosis* ; Tumor Suppressor Proteins/blood* ; Adaptor Proteins, Signal Transducing/blood* ; Retrospective Studies ; Nuclear Proteins/blood* ; Lymphocytes/cytology* ; Neutrophils/cytology* ; Female ; Male ; Prognosis ; Middle Aged

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 clinicopathological features of early gastric cancer ( EGC) with micropapillary pattern. Methods In 447 consecutive EGC patients at Changzhou No. 2 People′s Hospital admitted from January 2006 to December 2016, 8 ( 1. 8％) with micropapillary adenocarcinoma (≥5％) were enrolled in the observation group and the remaining 439 were included in the control group. Clinicopathologic features including age, gender, gross pattern, tumor location, size, invasion depth, lymphovascular invasion, lymphatic metastasis and pathological stage were analyzed and compared between the two groups. Results There were no significant differences between the two groups in age, gender, gross pattern, tumor location or size (all P>0. 05). The observation group showed significantly more frequent submucosal invasion ( 100. 0％, 8/8 ) , lymphovascular invasion ( 62. 5％, 5/8 ) , lymphatic metastasis (62. 5％, 5/8), and higher pathological stage (Ⅱ+Ⅲ 25. 0％, 2/8) compared with those in the control group, which were 52. 4％ ( 230/439 ) , 9. 1％ ( 40/439 ) , 13. 9％ ( 61/439 ) , and 5. 9％ ( 26/439 ) , respectively ( all P<0. 05 ) . Conclusion EGC with micropapillary pattern is rare with a high liability to lymphovascular invasion, lymphatic metastasis, and higher pathological stage, compared to EGC without micropapillary pattern.

Objective To explore a clear picture of the health human resources allocation in tertiary general hospitals in Beijing ,and propose strategies to optimize the configuration of human resources at the same level hospitals ,so as to improve the medical service quality for society. Methods Basic operational data and human resources configuration of 16 tertiary general hospitals with more than 800 beds in Beijing were col?lected by using clustering sampling and literature review ,and then a descriptive analysis of the human resource configuration data at the same level hospitals was carried out by SPSS18.0 and Excel2010. Results The number of patients increased year by year,but the average days of hospitaliza?tion showed a downward trends during 2009?2011. According to the previous way of beds to determine personnel ,there was significantly different from the actual situation. A significant quantitative correlation was foung between the physicians and the nurses,pharmacists,medical laboratory technician,and the ratio between physicians and these staffs is stable. Conclusion With the development of hospital service and increase of health human resources,health manpower ratio has changed significantly in tertiary general hospitals. A stable proportion of physicians can be used as the reference standard for hospital human resources configuration at the same level hospitals.

OBJECTIVETo assess the predictive value of Neuropad test on occurrence of diabetic foot ulceration (DFU) among type 2 diabetic patients.

METHODSWe divided 725 cases of type 2 diabetic patients into the high-risk and the non-high-risk groups of DFU based on the results of vibration perception thresholds(VPT) examination, which was widely used as a criteria for predicting DFU. Receiver operating characteristic (ROC) analysis was used to compare the effectiveness of Neuropad with 10 g Semmes-Weinstein monofilament (10 g SWMF) testing in predicting the risk of DFU.

RESULTSAmong 725 patients of type 2 diabetes, 6.1% were at a high risk of DFU. Compared to non-high-risk group, patients in high-risk group had older age, longer diabetes duration, higher values of complete colour change time (CCC time) of Neuropad and higher abnormal rate of 10 g SWMF (P<0.01). CCC time of Neuropad was shown to be better in predicting the risk of DFU than 10 g SWMF, and the area under the ROC curve was about 0.8, and the best cut-off value was 22.25 min.

CONCLUSIONNeuropad is an effective means for predicting of the risk of DFU, and can be used to prevent diabetic foot ulceration.

Adult ; Aged ; Diabetic Foot ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Neurologic Examination ; methods ; Predictive Value of Tests ; Risk Assessment

BACKGROUND:Studies about low-frequency pulsed electromagnetic fields interfering with bone marrow mesenchymal stem cells proliferation and differentiation are many, but the Raman spectra of single stem cells irradiated in electromagnetic fields analyzed by surface Raman spectroscopy analysis are rarely reported. OBJECTIVE:To compare the difference in Raman spectra of bone marrow mesenchymal stem cells with or with no irradiation of 3 000 Hz pulsed electromagnetic fields. METHODS:Bone marrow mesenchymal stem cells isolated from Sprague-Dawley rats were cultured and identified. Passage 3 cells were inoculated into 6-wel plates and divided into two groups:pulsed electromagnetic field irradiation group and blank control group. After cultured for 7 days, cells in the two groups were transferred to physiological saline, and 30 cells were randomly col ected from each group. Four Raman spectra were harvested from each celland the average relative intensity of Raman spectra was calculated and compared between two groups. RESULTS AND CONCLUSION:There were the same Raman peaks in the two groups, and the waveforms were basical y same in the two group based on the curve mapping by origin 7.0 software. The peak value in the irradiation group was decreased compared with the blank control group. Laser optical tweezers Raman spectroscopy can be applied to study the biochemical changes of a single stem cellat the molecular level. The Raman spectra of bone marrow mesenchymal stem cells irradiated by 3 000 Hz pulsed electromagnetic fields differ from those without irradiation, and the peak also lowered after irradiation.

Objective To assess the predictive value of Neuropad test on occurrence of diabetic foot ulceration (DFU) among type 2 diabetic patients. Methods We divided 725 cases of type 2 diabetic patients into the high-risk and the non-high-risk groups of DFU based on the results of vibration perception thresholds(VPT) examination, which was widely used as a criteria for predicting DFU. Receiver operating characteristic (ROC) analysis was used to compare the effectiveness of Neuropad with 10 g Semmes-Weinstein monofilament (10 g SWMF) testing in predicting the risk of DFU. Results Among 725 patients of type 2 diabetes, 6.1% were at a high risk of DFU. Compared to non-high-risk group, patients in high-risk group had older age, longer diabetes duration, higher values of complete colour change time (CCC time) of Neuropad and higher abnormal rate of 10 g SWMF (P<0.01). CCC time of Neuropad was shown to be better in predicting the risk of DFU than 10 g SWMF, and the area under the ROC curve was about 0.8, and the best cut-off value was 22.25 min. Conclusion Neuropad is an effective means for predicting of the risk of DFU, and can be used to prevent diabetic foot ulceration.

Objective To assess the predictive value of Neuropad test on occurrence of diabetic foot ulceration (DFU) among type 2 diabetic patients. Methods We divided 725 cases of type 2 diabetic patients into the high-risk and the non-high-risk groups of DFU based on the results of vibration perception thresholds(VPT) examination, which was widely used as a criteria for predicting DFU. Receiver operating characteristic (ROC) analysis was used to compare the effectiveness of Neuropad with 10 g Semmes-Weinstein monofilament (10 g SWMF) testing in predicting the risk of DFU. Results Among 725 patients of type 2 diabetes, 6.1% were at a high risk of DFU. Compared to non-high-risk group, patients in high-risk group had older age, longer diabetes duration, higher values of complete colour change time (CCC time) of Neuropad and higher abnormal rate of 10 g SWMF (P<0.01). CCC time of Neuropad was shown to be better in predicting the risk of DFU than 10 g SWMF, and the area under the ROC curve was about 0.8, and the best cut-off value was 22.25 min. Conclusion Neuropad is an effective means for predicting of the risk of DFU, and can be used to prevent diabetic foot ulceration.