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.

Allergic conjunctivitis is a common ocular inflammatory disease, with intense itching being the most typical and distressing symptom for patients. In recent years, with the in-depth study of the interaction between the nervous and immune systems, significant progress has been made in understanding the mechanism of itching in allergic conjunctivitis. This review elaborates on the neurobiological basis of itching in allergic conjunctivitis, with a focus on the complex dialogue between immune cells and sensory neurons, particularly the core role of the IL-33-ST2-CGRP signaling axis in mediating itching. Additionally, this article introduces new findings in genetic susceptibility research, including the identification of susceptibility genes for allergic conjunctivitis through transcriptome-wide association studies. The sensory nervous system not only transmits itch signals but also actively participates in the formation of antigen channels related to conjunctival goblet cells, thereby regulating the local uptake of allergens and the initiation of the immune response. Moreover, targeted novel therapeutic strategies offer hope for patients with refractory allergic conjunctivitis. Exploring the molecular and cellular mechanisms of itching in allergic conjunctivitis will provide a theoretical basis for the development of more effective treatment methods.

The introduction of immunotherapy has changed the traditional paradigms in cancer treatment and has demonstrated substantial clinical benefits across various malignancies. However, this progress is accompanied with emerging challenges, such as immune evasion and low response rates to immunotherapy. As an immunomodulatory molecule, zymogen granule protein 16 (ZG16) plays a crucial role in immunotherapy by inhibiting the binding of programmed death 1 (PD-1) to its ligand PD-L1, preventing immune evasion and restoring the immune system's ability to recognize and eliminate tumor cells. ZG16 is downregulated in multiple gastrointestinal tumors, and its regulatory mechanisms vary depending on the tumor type. ZG16 expression is closely associated with patient prognosis, and it has been identified as a favorable prognostic marker in colorectal cancer. This article provides a systematic overview of the structural characteristics, expression regulation mechanisms, and antitumor immune functions of ZG16.

Objective To investigate the preventive and therapeutic effects of ethanol extracts derived from three sources of traditional Chinese medicine: Stellera chamaejasme L., Euphorbia fischeriana Steud. and Euphorbia kansuensis Prokh., on imiquimod （IMQ）-induced psoriasis in mice. Methods Thirty-six male BALB/c mice were randomly divided into the following 6 groups with 6 mice in each group: blank control, model, Stellera chamaejasme, Euphorbia fischeriana, Euphorbia kansuensis, and calcipotriol. Psoriasis area and severity index（PASI） scores were used to record the changes of skin lesions in every group; Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of skin and measure the thickness of the epidermis. Immunohistochemistry was used to detect the expression of nuclear antigen Ki67 in the skin tissues of mice. Results Compared with the model group, the three kinds of ethanol extracts could reduce the PASI score, inhibit epidermal thickening, and decrease expression of Ki67 in the psoriasis mice. Among them, the therapeutic effect of Stellera chamaejasme was the most significant and it was better than the commonly used topical drug calcipotriol. Conclusion The ethanol extract of Stellera chamaejasme had good anti-psoriatic activity, which could inhibit the abnormal proliferation of keratinocytes, reduce the expression of Ki67, and significantly improve psoriasis-like skin lesions.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Objective To investigate the current situation of frailty in patients with home peritoneal dialysis and analyze its influencing factors,so as to provide bases for early identification of high-risk groups and targeted clinical intervention.Methods From October to December 2024,205 home-based peritoneal dialysis patients under long-term follow-up at a tertiary A hospital in Zhongshan,Guangdong Province,were selected by convenience sampling.The General Information Questionnaire,Fried Phenotype Scale,Nutritional Risk Screening Tool,Exercise Self-Efficacy Scale,and Social Support Rating Scale were used to investigate the influencing factors of frailty in home-based peritoneal dialysis patients by ordinal logistic regression analysis.Results A total of 201 valid questionnaires were collected.The prevalence of frailty among home-based peritoneal dialysis patients was 24.3％,while 39.3％were in the pre-frailty stage,and 36.3％showed no frailty.0rdinal logistic regression analysis revealed that age,residence location,primary disease,sleep status,serum albumin concentration,and exercise self-efficacy level were influencing factors of frailty in the home peritoneal dialysis patients(P＜0.05).Conclusion The incidence of frailty in patients with home peritoneal dialysis is higher,and patients with advanced age,living in rural areas,other types of primary diseases,insomnia,low serum albumin concentration and low exercise self-efficacy are more likely to develop frailty.Specialist doctors and nurses of peritoneal dialysis should pay attention to the early screening of frailty in patients with peritoneal dialysis at home,and take personalized intervention measures to prevent or delay the occurrence of frailty according to the relevant risk factors.

Objective To study the application of autologous natural killer(NK)cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients.Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group(31 cases,given supportive treatment combined with sunitinib malate capsules)and cell group(30 cases,autologous NK cells combined with targeting group)according to the patient's willingness to treat combined with propensity score matching.6 weeks was a treatment cycle,and all patients were treated for 4 cycles.The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed.The levels of serum cytokines,tumor markers,lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment.Results After 4 cycles of treatment,the objective remission rate and disease control rate in the cell group were higher than those in the targeting group(P<0.05).After 4 cycles of treatment,the levels of serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF),carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment,and those in the cell group were lower than those in the targeting group(P<0.012 5).After 4 cycles of treatment,the levels of serum interleukin-2,interleukin-6,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+,CD4+,NK cells and CD4+/CD8+in the two groups were higher than those before treatment.The levels of serum interleukin-2,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+and NK cells in the cell group were higher than those in the targeting group(P<0.012 5).The level of CD8+in peripheral blood was lower than that before treatment(P<0.012 5),but there was no significant difference between the two groups(P>0.012 5).During the treatment,there was no significant difference in the incidence of diarrhea,nausea and vomiting,alopecia,liver function damage,decreased platelet level and decreased neutrophil level between the cell group and the targeting group(P>0.05).Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines,reduce the level of tumor markers,regulate the function of lymphocytes and immune function,and had a good therapeutic effect.At the same time,it would not increase the incidence of adverse reactions,and the safety was good.

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

A detection model based on Gramian angular field(GAF)and parallel KConvNeXt network is proposed for accurately detecting the abnormal conditions caused by sample needle blockage in the sampling system during the sampling,thus improving the testing accuracy and detection efficiency of automated biochemical analyzers.GAF-based method is employed to transform the time series of one-dimensional pressure signals into two-dimensional image representations.Subsequently,an improved attention mechanism integrated with a parallel dual-channel KConvNeXt network is used to classify the pressure signals,and achieves a final classification accuracy of 94.58%.The experimental results show that the proposed method can effectively capture the key characteristics of the pressure signals,offering an efficient solution for the anomalous pressure detection in biochemical analyzer sampling system and exhibiting important practical significance.