ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Pancreatic ductal adenocarcinoma is profoundly treatment-resistant, due to intrinsic properties of the tumor cells and the complex tumor microenvironment. Consequently, surgical resection of the primary tumor is still the only intervention that significantly prolongs patient survival. This points at an urgent need for more effective (neo)adjuvant strategies to increase the fraction of patients eligible to surgery and to counter post-surgery disease recurrence. The advent of single-cell RNA-sequencing has created an opportunity for the development of a highly potent, patient-tailored adjuvant treatment that is based on the infusion of genetically engineered autologous T-cells armed with tumor-reactive T-cell receptors as identified in the patient′s own tumor sample.

Objective To explore the predictive efficacy of several multimodal MRI-based machine learning models for the promoter methylation states of O6-methylguanine-DNA methyltransferase(MGMT)of glioblastoma muliforme(GBM)patients in terms of the GBM heterogeneity and the complexity of the tumor microenvironment.Methods Firstly,the multimodal MRI images of 317 GBM patients from The University of Pennsylvania Glioblastoma(UPENN-GBM)dataset were pre-processed,with four sequences involved in including T1-weighted imaging(T1WI)sequence,T1-weighted contrast-enhanced imaging(T1CE)sequence,T2-weighted imaging(T2WI)sequence and fluid-attenuated inversion recovery(FLAIR)sequence,and the radiomics features were extracted for two regions of interest(ROIs)such as the tumor core region and the tumor edema region.Secondly,the data of the 317 GBM patients were randomly divided into a training set(254 cases)and a test set(63 cases),which underwent normalization with Z-scores and feature selection and dimensionality reduction with Lasso regression.Finally,three models were established respectively with particle swarm optimization-support vector machine(PSO-SVM),C-support vector classification(C-SVC)and adaptive boosting(adaptive boosting(Adaboost)algorithms,and the predictive efficacy of the three models for glioblastoma multiforme MGMT promoter methylation states were evaluated in terms of accuracy and AUC.Results The Adaboost model based on T2WI sequence and radiomics features of the tumor core region had the highest predictive efficacy with accuracy and AUC values of 67％and 0.74,respectively,higher than those of other combinations of sequences,models and regions of interest.Conclusion The multimodal MRI-based machine learning models can be used for the prediction of glioblastoma multiforme MGMT promoter methylation states,which provides powerful support for personalized treatment and prognostic assessment of GBM.[Chinese Medical Equipment Journal,2025,46(6):7-13]

Medical device related infections caused by bacteria are common complications in clinical practice,and preventing bacterial colonization on the surface of medical materials is one of the important challenges in the medical field.Therefore,there is an urgent need to construct medical coatings that combine antibacterial properties and biocompatibility.In this study,a γ-polyglutamic acid(γ-PGA)complex with long-chain alkyl quaternary ammonium salts formed by electrostatic and hydrophobic interactions was prepared,which was insoluble in water but soluble in organic solvents(e.g.,ethanol),and was capable of constructing antimicrobial coatings on the surfaces of medical materials in a simple and efficient manner.The bactericidal effect of the coating was verified using viable bacteria counting experiments,and the results showed that the bactericidal rate of the coated thermoplastic polyurethane(TPU)membrane against Staphylococcus aureus was greater than 99.9%compared with that of the uncoated TPU membrane.In addition,a cytotoxicity assay was performed using the L929 fibroblast and cell proliferation detection kit(CCK-8),which showed that the survival rate of L929 fibroblasts on coated TPU was greater than 90%.Meanwhile,the hemolysis rate of coated erythrocytes was tested using fresh rabbit red blood cells(RBCs),and the hemolysis rate on the coated TPU surface was 1.5%.The above results indicated that the coating had good biocompatibility.The preparation method of medical antibacterial coating reported in this study provided a new idea for preventing bacterial infections related to implantable/interventional medical devices.

Objective:To investigate the clinical characteristics of patients with high-myopia macular hole retinal detachment (MHRD) combined with choroidal detachment and to preliminarily analyze factors associated with postoperative hole closure.Methods:A retrospective clinical case series study. A total of 68 patients with high myopia (68 eyes) with MHRD diagnosed by Department of Ophthalmology, Peking University People’s Hospital from January 2019 to April 2024 were included in this study. Among them, there were 14 males (14 eyes) and 54 females (54 eyes). The mean age was (61.10±9.66) years. All eyes were treated with pars plana vitrectomy (PPV) combined with silicone oil or gas filling. Best corrected visual acuity (BCVA), intraocular pressure, and B-mode ultrasonography were performed. The BCVA test was performed using the Snellen visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The range of choroidal detachment was defined according to the number of involved quadrants observed in B-mode ultrasound or surgery, which was divided into 1 to 4 quadrants. Axial length (AL) was measured under retinal reattachment. In 68 eyes, there were 17 eyes with choroidal detachment and 51 eyes without choroidal detachment, respectively. There were 17 eyes with choroidal detachment, and the detachment range involved 1, 2, 2 and 12 eyes in 1, 2, 3 and 4 quadrants, respectively. During operation, 13% C 3F 8 was filled in 2 eyes, all of which were not complicated with choroidal detachment. 66 eyes were filled with silicone oil. According to whether the patients were complicated with choroidal detachment, the patients were divided into the group without choroidal detachment and the group with choroidal detachment. Independent sample t test, Welch two-sample t test or Mann-Whitney U test were used for comparison between groups. Generalized linear regression and logistic regression were used to analyze the relationship between the aperture size of postoperative unclosed holes and the closed hole after surgery and clinical factors. Results:At 3 months after surgery, the logMAR BCVA of the affected eye was 1.29±0.43, with a preoperative to postoperative difference ranging from -1.60 to 0.70 (-0.51±0.51) logMAR units. The AL ranged from 26.6 to 34.3 (29.60±2.12) mm. Among 68 eyes, macular hole of 37 (54.4%, 37/68) eyes were open and 31 (45.6%, 31/68) eyes were closed, respectively. The hole diameter of the open eye was (753±424) μm. There was no significant difference in age, course of disease and AL between the two groups ( W=412.0, 477.5, 427.0; P>0.05). Before operation, BCVA in patients with choroidal detachment was worse ( W=257.5) and intraocular pressure was lower ( t=4.051) in patients with choroidal detachment compared with those without choroidal detachment, with statistical significance ( P<0.05). At 3 months after surgery, BCVA in patients with choroidal detachment was significantly worse than that in patients without choroidal detachment, with statistical significance ( W=284.0, P<0.05). There were no significant differences in logMAR BCVA difference ( t=0.616) and macular hole closure rate ( χ 2=0.000) before and after surgery ( P>0.05). The reoperation rate of retinal detachment due to persistent or recurrent retinal detachment was significantly higher in the group with choroid detachment than in the group without choroid detachment, and the difference was statistically significant (odds ratio=6.424, P<0.05). Logistic regression analysis showed that young age was significantly correlated with macular hole closure failure after surgery ( β=0.077, P=0.015). There was no correlation between AL, duration of disease, BCVA before surgery, intraocular pressure, wether combined with choroid detachment range and postoperative hole closure ( β=-0.072, 0.000, 0.672, -0.085, -0.391; P>0.05). Conclusions:Concomitant choroidal detachment adversely affected on both pre-operative and post-operative visual acuity in high myopia MHRD. It is closely associated with the risk of recurrent retinal detachment and the needs of multiple operations, but has no significant effect on hole closure rate. Lower age of onset may be a risk factor for macular hole closure.

Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.

Abstract To clarify the relationship between sports participation and adolescent suicide risk, as well as its underlying mechanisms for preventing suicidal behaviors, the study employs a literature review approach to analyze, synthesize, and summarize relevant research. The findings reveal that physical exercise can reduce suicide rates among middle school students, with high intensity aerobic exercise performed 5-7 days per week demonstrating the most significant effect. However, daily physical activity and muscle strengthening exercises show no significant correlation with suicide related behaviors. The mechanisms through which physical activity reduces the risk of suicide among adolescents include emotional release leading to self help skills, helping adolescents build social connections, and improving physical and brain function. It is recommended that families and schools help adolescents discover the joy of participating in sports, assist in forming sports teams, and ensure at least 60 minutes of moderate to vigorous physical activity daily to reduce the risk of suicidal behavior among adolescents.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*