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.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide(FeNO)and conventional ventilatory lung function parameters in diagnosing bronchial asthma(referred to as"asthma")in children.Methods A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group,and 85 healthy children undergoing routine health checks as the control group.The study compared the differences in serum 14-3-3β protein concentrations between the two groups,analyzed the correlation of serum 14-3-3β protein with clinical indices,and evaluated the diagnostic efficacy of combining 14-3-3β protein,FeNO,and conventional ventilatory lung function parameters for asthma in children.Results The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group(P<0.001).Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E,and a negative correlation with conventional ventilatory lung function parameters(P<0.05).Cross-validation of combined indices showed that the combination of 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume had an area under the curve of 0.948 for predicting asthma,with a sensitivity and specificity of 88.9%and 93.7%,respectively,demonstrating good diagnostic efficacy(P<0.001).The model had the best extrapolation.Conclusions The combination of serum 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume can significantly improve the diagnostic efficacy for asthma in children.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

The allocation of policy attention is a crucial element in policy process.Under China's administrative system,the policy design pattern based on pilot exploration,experience accumulation,and innovation diffusion in the healthcare sector needs to be interpreted by focusing on the allocation of policy attention and the opening of the policy decision-making agenda in the specific policy context of pilot innovation.This study is based on textual data from the State Council's briefing on deepening medical and healthcare system reform.Utilizing topic modeling analysis techniques,we attempt to analyze the interactive relationship between the national-level medical reform policy framework and local institutional innovation,as well as the structural characteristics of local institutional innovation cases.The study found that the textual content of institutional innovation cases further reveals the goal value and effects of policies from a policy discourse perspective and carries the dual function of addressing the problems of the previous policy agenda setting and opening a new round of policy agenda.