Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective:To study the effect of lower limb hip and knee hyperextension compensation on gait characteristics of Parkinson's disease patients at different stages.Method:A total 149 patients with primary Parkinson's disease admitted to Huashan Hospital of Fudan Universi-ty from 2020 to 2022 were divided into three groups based on the duration of the disease:short course group(duration≤5years),medium course group(5 years10 years).Additionally,37 healthy subjects were selected as the control group.A wearable gait acquisition device was used to collect the temporal and spatial parameters of gait and movement parameters of the three groups of patients and the healthy control group.The differences in gait parameters among the groups were compared.Result:The gait parameters of Parkinson's disease patients changed significantly with the progression of the dis-ease.Compared with the healthy control group,the stride length and stride speed of Parkinson's disease pa-tients showed the most significant impairment.Additionally,the angles of hip flexion and knee flexion during walking decreased significantly with the progression of the disease and were proportional to the duration of the disease,while the angles of compensatory activity of hip extension and knee extension increased in the early stage of the disease,and the compensatory function gradually subsided with the progression of the disease(the regression of hip extension compensation was earlier than that of knee extension compensation),leading to the gradual aggravation of abnormal gait.Conclusion:The compensatory mechanism of hip and knee hyperextension in the lower extremities presents a dynamic evolution pattern through the course of Parkinson's disease.This has guiding significance for function-al diagnosis,rehabilitation treatment and disease prediction in Parkinson's disease.

Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

We retrospectively analyzed 8 patients who had been on hemodialysis for over 30 years from two dialysis centers in Dalian, China. A literature review was conducted by searching PubMed, CNKI, Wanfang databases,and Chinese Medical Journal Network for cases of patients on hemodialysis for over 30 years. The 8 patients had good baseline health, with chronic glomerulonephritis as the primary renal disease and no comorbidities before initiating dialysis. They started hemodialysis between 21 and 38 years of age, predominantly using arteriovenous fistulas for vascular access. Dialysis was regular and adequate (KT/V 1.23-1.88). Key laboratory parameters, including hemoglobin (88-118 g/L), albumin (27.7-39.7 g/L), calcium (1.88-2.55 mmol/L), and phosphate (0.76-1.99 mmol/L), were generally within target ranges. Body mass index ranged from 15.20 to 22.96 kg/m2. This literature review of the study included 12 case reports and 4 orginal articles. Factors influencing long-term survival included baseline health status, primary renal disease, absence of comorbidities before dialysis initiation, age at dialysis initiation, type of vascular access, dialysis adequacy, complication management, and medical support. Standardized management and timely correction of complications can significantly improve prognosis and enhance long-term survival in hemodialysis patients.

Objectives:This study aims to explore the value of the baseline extracellular volume(ECV)measured by cardiac magnetic resonance(CMR)in predicting cardiac response in patients with light chain cardiac amyloidosis(AL-CA)after treatment.Methods:This single-center retrospective cohort study included AL-CA patients diagnosed between May 2020 and March 2023.Baseline ECV measurement and other relevant parameters were derived from CMR.Therapeutic cardiac response was assessed through serial measurements of N-terminal pro-B-type natriuretic peptide(NT-proBNP).Complete recovery was defined as achieving NT-proBNP≤350 pg/ml post-treatment.Patients demonstrating>60%reduction from baseline NT-proBNP without attaining complete response criteria were classified as very good partial recovery.Those showing 31%-60%decreases from baseline NT-proBNP without meeting the threshold for very good partial recovery were qualified as partial recovery,while≤30%reductions from baseline were considered as non-recovery.The study evaluated two endpoints:the initial emergence of any cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery)and the subsequent attainment of optimal cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery).The patients were divided into two groups based on whether they experienced cardiac recovery at the end of follow-up:the recovery group(n=24,comprising 7 with partial recovery,14 with very good partial recovery,and 3 with complete recovery)and the non-recovery group(n=16).Cox Proportional hazards regression models were used to analyse the impact of baseline ECV on the cardiac recovery.The Kaplan-Meier method and log-rank test were used to assess and compare the probability and timing of cardiac recovery between different baseline ECV groups.Results:Among the 40 patients,28(70%)were male,with a mean age of(58?±?8)years.32 patients(80%)had the λ subtype of AL-CA.During a median follow-up of 568(155,1 049)days,15 patients showed partial cardiac recovery at 60 days post-treatment,and 3 patients achieved very good partial cardiac recovery;by 720 days of treatment and until the end of follow-up,3 patients achieved complete cardiac recovery.Multivariate Cox regression analysis revealed that baseline ECV(HR=0.937,95%CI:0.879-0.999,P=0.045)and daratumumab-based regimens(HR=3.279,95%CI:1.098-9.796,P=0.033)were significant predictors of the initial cardiac recovery.Similarly,baseline ECV(HR=0.931,95%CI:0.867-1.000,P=0.048)and daratumumab-based regimens(HR=3.132,95%CI:1.052-9.319,P=0.040)were also independent predictors for the best cardiac recovery.Kaplan-Meier analysis demonstrated that patients with baseline ECV<54%achieved an earlier first cardiac recovery than those with baseline ECV≥54%(log-rank P=0.014)and the group with baseline ECV<55%were more likely to achieve the best cardiac recovery compared to those with baseline ECV≥55%(log-rank P=0.006).Conclusions:Baseline ECV measured by CMR can serve as an independent predictor of cardiac recovery in AL-CA patients after treatment.Lower baseline ECV levels are associated with a faster and more favorable cardiac recovery.The daratumumab-based regimens demonstrated superior cardiac recovery outcomes.

Objective:To investigate the level of urinary serine protease(Corin) in early diabetic kidney disease(DKD) and its correlation with clinical stage.Methods:One hundred and seventy-three patients with type 2 diabetes mellitus(DM) from two tertiary A hospitals in Henan, diagnosed between April 2023 and December 2023 were selected as the research group, and 120 healthy subjects were selected as the control group. Basic clinical information and laboratory data were collected, and urinary Corin level was detected. DM patients were classified into G1-G5 stages based on estimated glomerular filtration rate(eGFR), and those in the early DKD stages(G1-G3) were further divided into A1-A3 subgroups based on urinary albumin/creatinine ratio(ACR). Spearman correlation analysis was performed to assess relationships between urinary Corin and other indicators, linear regression analysis identified factors influencing urinary Corin in early DKD patients, logistic regression analysis evaluated the risk factors for early DKD, and receiver operating characteristic(ROC) curve analysis determined the diagnostic value of urinary Corin in early DKD. Results:Urinary Corin levels were significantly higher in early DKD patients compared to healthy controls, with levels increasing as ACR rose( P<0.05). Urinary Corin was positively associated with serum creatinine( r=0.570), urea( r=0.458), cystatin C( r=0.693), ACR( r=0.616), urinary transferrin( r=0.448), urinary α1 microglobulin( r=0.507), urinary n-acetyl-β-D-glucosaminase( r=0.388) and A subgroup( r=0.692) while was negatively correlated with eGFR( r=-0.647), albumin( r=-0.312)(all P<0.05). eGFR was the only independent factor affecting urinary Corin. After adjusting for confounding factors in logistic regression analysis, urinary Corin was still an independent influencing factor for early DKD. ROC curve analysis indicated that urinary Corin had a diagnostic AUC of 0.842(95% CI 0.791-0.892, P<0.001), with a cut-off value of 2 226.04 pg/mL, sensitivity of 0.712, and specificity of 0.858 for early DKD diagnosis. Conclusions:Urinary Corin was elevated in early DKD patients and correlated with clinical stage. Urinary Corin is an independent factor of early DKD, and a reliable predictor of early DKD diagnosis.

Objective:To analysis the possible behavior of coders in the reform of Diagnosis Related Groups(DRG)payment mode.Methods:To collect through questionnaires the possible coders'behaviors,and extract the common factors of possible behaviors according to factor analysis,and cluster the coders by the K-means clustering method.Results:Classify the possible coders'behaviors into positive behaviors such as following coding norms and standards,and negative behaviors such as directly coding without detailed reading of medical records.Less than 25 years old were more inclined to adopt negative behaviors,and associate senior titles and higher cognitive level of DRG were more inclined to adopt positive behaviors.The coders are divided into"positive group"who tend to take positive behaviors and"negative group"who take negative behaviors.Conclusion:Coders are more likely to adopt positive behavior,and we should be pay attention to the impact of different demographic characteristics on coders.To adopt different management strategies for different categories of coders,and strengthen training through hierarchical classification,and enhance coders'cognitive of DRG are more conducive to the selection of positive behaviors.

Objective:To explore the experiences and needs of discharged patients with ischemic stroke during the implementation of home-based digital-intelligent blood pressure management.Methods:Using purposive sampling method, 13 acute ischemic stroke patients admitted to the Department of Neurology of Xuanwu Hospital of Capital Medical University and discharged to receive home-based digital-intelligent blood pressure management were selected for face-to-face semi-structured interviews between March and May 2024. Colaizzi 7-step analysis was used for the analysis.Results:A total of three themes and six sub-themes were extracted, namely, the double-edged effect under digital-intelligent empowerment (current situation of collision between technological novelty and cognitive generation gap, and contradiction between precision priority and lagging user experience), inertial resistance and behavioral reshaping in the process of digital-intelligent intervention (behavioral intervention exclusion under life inertia and self-efficacy enhancement driven by digital intelligence), and the "support disconnection" and the need for system reconstruction in home-based rehabilitation (professional guidance "vacuum" identity anxiety, and imbalance in the tension of family support networks) .Conclusions:Home-based blood pressure digital-intelligent management devices and programs for ischemic stroke patients need to be improved and developed. The role of multidisciplinary teams should be actively utilized, the digital divide should be emphasized, and post-disease family relationships should be reconstructed to further enhance patients' awareness of long-term blood pressure management.

Objectives:This study aims to explore the value of the baseline extracellular volume(ECV)measured by cardiac magnetic resonance(CMR)in predicting cardiac response in patients with light chain cardiac amyloidosis(AL-CA)after treatment.Methods:This single-center retrospective cohort study included AL-CA patients diagnosed between May 2020 and March 2023.Baseline ECV measurement and other relevant parameters were derived from CMR.Therapeutic cardiac response was assessed through serial measurements of N-terminal pro-B-type natriuretic peptide(NT-proBNP).Complete recovery was defined as achieving NT-proBNP≤350 pg/ml post-treatment.Patients demonstrating>60%reduction from baseline NT-proBNP without attaining complete response criteria were classified as very good partial recovery.Those showing 31%-60%decreases from baseline NT-proBNP without meeting the threshold for very good partial recovery were qualified as partial recovery,while≤30%reductions from baseline were considered as non-recovery.The study evaluated two endpoints:the initial emergence of any cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery)and the subsequent attainment of optimal cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery).The patients were divided into two groups based on whether they experienced cardiac recovery at the end of follow-up:the recovery group(n=24,comprising 7 with partial recovery,14 with very good partial recovery,and 3 with complete recovery)and the non-recovery group(n=16).Cox Proportional hazards regression models were used to analyse the impact of baseline ECV on the cardiac recovery.The Kaplan-Meier method and log-rank test were used to assess and compare the probability and timing of cardiac recovery between different baseline ECV groups.Results:Among the 40 patients,28(70%)were male,with a mean age of(58?±?8)years.32 patients(80%)had the λ subtype of AL-CA.During a median follow-up of 568(155,1 049)days,15 patients showed partial cardiac recovery at 60 days post-treatment,and 3 patients achieved very good partial cardiac recovery;by 720 days of treatment and until the end of follow-up,3 patients achieved complete cardiac recovery.Multivariate Cox regression analysis revealed that baseline ECV(HR=0.937,95%CI:0.879-0.999,P=0.045)and daratumumab-based regimens(HR=3.279,95%CI:1.098-9.796,P=0.033)were significant predictors of the initial cardiac recovery.Similarly,baseline ECV(HR=0.931,95%CI:0.867-1.000,P=0.048)and daratumumab-based regimens(HR=3.132,95%CI:1.052-9.319,P=0.040)were also independent predictors for the best cardiac recovery.Kaplan-Meier analysis demonstrated that patients with baseline ECV<54%achieved an earlier first cardiac recovery than those with baseline ECV≥54%(log-rank P=0.014)and the group with baseline ECV<55%were more likely to achieve the best cardiac recovery compared to those with baseline ECV≥55%(log-rank P=0.006).Conclusions:Baseline ECV measured by CMR can serve as an independent predictor of cardiac recovery in AL-CA patients after treatment.Lower baseline ECV levels are associated with a faster and more favorable cardiac recovery.The daratumumab-based regimens demonstrated superior cardiac recovery outcomes.

Objective:To study the effect of lower limb hip and knee hyperextension compensation on gait characteristics of Parkinson's disease patients at different stages.Method:A total 149 patients with primary Parkinson's disease admitted to Huashan Hospital of Fudan Universi-ty from 2020 to 2022 were divided into three groups based on the duration of the disease:short course group(duration≤5years),medium course group(5 years10 years).Additionally,37 healthy subjects were selected as the control group.A wearable gait acquisition device was used to collect the temporal and spatial parameters of gait and movement parameters of the three groups of patients and the healthy control group.The differences in gait parameters among the groups were compared.Result:The gait parameters of Parkinson's disease patients changed significantly with the progression of the dis-ease.Compared with the healthy control group,the stride length and stride speed of Parkinson's disease pa-tients showed the most significant impairment.Additionally,the angles of hip flexion and knee flexion during walking decreased significantly with the progression of the disease and were proportional to the duration of the disease,while the angles of compensatory activity of hip extension and knee extension increased in the early stage of the disease,and the compensatory function gradually subsided with the progression of the disease(the regression of hip extension compensation was earlier than that of knee extension compensation),leading to the gradual aggravation of abnormal gait.Conclusion:The compensatory mechanism of hip and knee hyperextension in the lower extremities presents a dynamic evolution pattern through the course of Parkinson's disease.This has guiding significance for function-al diagnosis,rehabilitation treatment and disease prediction in Parkinson's disease.