INTRODUCTION:Amyloid burden may relate to semantic fluency through tau and astrocytic pathways, but their contributions remain unclear. METHODS:In this cross-sectional study, we analyzed 210 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with amyloid positron emission tomography (PET), tau PET, plasma glial fibrillary acidic protein (GFAP), and animal fluency. Joint mediation models estimated indirect effects through language-network tau and GFAP, with subgroup analyses in amyloid beta (Aβ)-positive participants. RESULTS:In the full sample, both tau and GFAP significantly mediated the association between amyloid burden and animal fluency, with a larger, more robust estimate for tau. Direct effects were non-significant. Among Aβ-positive participants, tau mediation remained significant, whereas GFAP mediation was attenuated. The dual-mediator model showed a significant combined indirect effect (average causal mediation effects [ACME] = -0.211). Exploratory analyses suggested possible apolipoprotein E APOE ε4 moderation of the tau-mediated pathway. DISCUSSION:Amyloid-related semantic fluency impairment was associated with language-network tau and astrocytic reactivity, with tau the stronger mediator, supporting biomarker-defined heterogeneity in language vulnerability across the Alzheimer's continuum.

IntroductionGliomas are the most common primary intracranial tumors, known for their high invasiveness and destructiveness. Sialic acid-binding immunoglobulin-like lectin 7 (SIGLEC7) is present in various immune cells, especially macrophages, and significantly affects immune homeostasis and cancer cell response. However, research on the role and prognostic impact of SIGLEC7 in glioma patients is currently limited.MethodsWe utilized transcriptomic data from 702 glioma patients in The Cancer Genome Atlas (TCGA) and 693 glioma patients in the Chinese Glioma Genome Atlas (CGGA), along with clinical samples we collected, to comprehensively investigate the impact of SIGLEC7 on glioma expression patterns, biological functions, and prognostic value. We focused on its role in glioma-related immune responses and immune cell infiltration and analyzed its expression at the single-cell level. Finally, we validated the role of SIGLEC7 in gliomas through tissue and cell experiments.ResultsSIGLEC7 expression was significantly increased in glioma patients with malignant characteristics. Survival analysis indicated that glioma patients with high SIGLEC7 expression had significantly lower survival rates. Gene function analysis revealed that SIGLEC7 is primarily involved in immune and inflammatory responses and is strongly negatively correlated with tumor-associated immune regulation. Additionally, the expression of most immune checkpoints was positively correlated with SIGLEC7, and immune cell infiltration analysis clearly demonstrated a significant positive correlation between SIGLEC7 expression and M2 macrophage infiltration levels. Single-cell analysis, along with tissue and cell experiments, confirmed that SIGLEC7 enhances macrophage polarization towards the M2 phenotype, thereby promoting glioma invasiveness through the immunosuppressive effects of M2 macrophages. Cox regression analysis and the establishment of survival prediction models indicated that high SIGLEC7 expression is an unfavorable prognostic factor for glioma patients.DiscussionHigh SIGLEC7 expression predicts poor prognosis in glioma patients and is closely associated with M2 macrophages in the tumor environment. In the future, SIGLEC7 may become a promising target for glioma immunotherapy.

BackgroundAdvancements in modern medicine have extended human lifespan, but they have also led to an increase in age-related diseases such as Alzheimer’s disease (AD) and atherosclerosis (AS). Growing research evidence indicates a close connection between these two conditions.MethodsWe downloaded four gene expression datasets related to AD and AS from the Gene Expression Omnibus (GEO) database (GSE33000, GSE100927, GSE44770, and GSE43292) and performed differential gene expression (DEGs) analysis using the R package “limma”. Through Weighted gene correlation network analysis (WGCNA), we selected the gene modules most relevant to the diseases and intersected them with the DEGs to identify crosstalk genes (CGs) between AD and AS. Subsequently, we conducted functional enrichment analysis of the CGs using DAVID. To screen for potential diagnostic genes, we applied the least absolute shrinkage and selection operator (LASSO) regression and constructed a logistic regression model for disease prediction. We established a protein-protein interaction (PPI) network using STRING (https://cn.string-db.org/) and Cytoscape and analyzed immune cell infiltration using the CIBERSORT algorithm. Additionally, NetworkAnalyst (http://www.networkanalyst.ca) was utilized for gene regulation and interaction analysis, and consensus clustering was employed to determine disease subtypes. All statistical analyses and visualizations were performed using various R packages, with a significance level set at p<0.05.ResultsThrough intersection analysis of disease-associated gene modules identified by DEGs and WGCNA, we identified a total of 31 CGs co-existing between AD and AS, with their biological functions primarily associated with immune pathways. LASSO analysis helped us identify three genes (C1QA, MT1M, and RAMP1) as optimal diagnostic CGs for AD and AS. Based on this, we constructed predictive models for both diseases, whose accuracy was validated by external databases. By establishing a PPI network and employing four topological algorithms, we identified four hub genes (C1QB, CSF1R, TYROBP, and FCER1G) within the CGs, closely related to immune cell infiltration. NetworkAnalyst further revealed the regulatory networks of these hub genes. Finally, defining C1 and C2 subtypes for AD and AS respectively based on the expression profiles of CGs, we found the C2 subtype exhibited immune overactivation.ConclusionThis study utilized gene expression matrices and various algorithms to explore the potential links between AD and AS. The identification of CGs revealed interactions between these two diseases, with immune and inflammatory imbalances playing crucial roles in their onset and progression. We hope these findings will provide valuable insights for future research on AD and AS.

Objective:Vaginitis is a disease characterized by inflammation of the vagina, commonly caused by bacterial, fungal, or parasitic infections, which significantly impacts the physical and psychological health of patients. Stem cell therapy, especially using cells with enhanced cytokine secretion capabilities after induction, presents a promising treatment approach. This study aims to explore a method to induce umbilical cord mesenchymal stem cells (UC-MSCs) to secrete higher levels of cytokines and evaluate their efficacy in treating vaginitis. Methods:We developed an induction method using a combination of growth factors and nutrients to significantly stimulate cytokine secretion from UC-MSCs and conducted a comprehensive evaluation of the induced UC-MSCs (iUC-MSCs). This evaluation included cytokine secretion capacity, secretion characteristics, cell phenotype, lipid formation ability, and safety before and after induction. Subsequently, we applied the iUC-MSCs to a vaginitis disease model and assessed the therapeutic effects of iUC-MSCs through pathology and related scoring. Results:Flow cytometry analysis showed no significant differences in the expression of phenotypic markers of UC-MSCs before and after induction. AAH-BLG-1 antibody microarray results indicated that cytokine levels secreted by iUC-MSCs were significantly higher than those of the UC-MSCs group. Additionally, iUC-MSCs exhibited improved lipid formation ability and cell proliferation activity compared to the non-induced group. Following this, iUC-MSCs were used to treat the vaginitis model. Western blot analysis post-cell transplantation revealed a significant reduction in inflammatory factor expression in the iUC-MSCs group. Immunofluorescence results showed that compared to the UC-MSCs group and the control group, iUC-MSCs had significantly higher expression levels of COL I, CD31, and cytokeratin CK. The iUC-MSCs group demonstrated superior regeneration and repair effects at the injury site compared to other control groups. Conclusion:Compared to UC-MSCs, iUC-MSCs exhibited higher cytokine secretion and proliferation capacities. Transplantation of iUC-MSCs not only reduced inflammation levels at the lesion site but also promoted angiogenesis, epithelial keratinization, and collagen type I restoration. These combined effects significantly enhanced the regeneration and repair of the lesion site.

Amyotrophic lateral sclerosis (ALS) is a multi-factor neurodegenerative disease, characterized by the loss of motor neurons. TAR DNA-binding protein 43 (TDP-43) mutation, accumulation and aggregation, as well as oxidative stress are recognized as major pathological denominators and biochemical markers for ALS. Recently, human umbilical cord mesenchymal stem cell-derived conditioned medium (UC-CM) has been introduced to treat ALS patients. However, there is no research for the protective effect of UC-CM on the TDP-43 model of ALS. In this study, we evaluated the potential neuroprotective effect of UC-CM on a cellular ALS model expressing TDP-43mutant M337V, as well as its underlying mechanism. We found that 24 h UC-CM treatment could protect M337V expressing motor neurons by increasing cell viability and reducing LDH leakage. Furthermore, the ag-gregation of M337V, generation of ROS, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), protein carbonyl and 8-OHdG were also reduced by UC-CM, indicating that UC-CM protected cells by reducing oxidative damage. Moreover, UC-CM significantly increased the expression of nuclear Nrf2 and its downstream enzyme HO1. The Nrf2 translocation inhibitor ML385 could inhibit the effect of UC-CM on the cell viability and aggregate of M337V. Our results suggest that UC-CM protect cells against M337V expression by its strong antioxidative effect via Nrf-2/HO-1 axis activation.

RNA N6-methyladenosine (m6A) regulators are essential for a variety of biological functions, such as early development, viral infections, and cancer. However, their roles in Alzheimer disease (AD) are still not very clear. Here, 16 significant m6A regulators were identified using difference analysis between AD patients and non-demented controls based on the GSE132903 dataset from the Gene Expression Omnibus database. Using these 16 m6A regulators, a nomogram model was established to predict the prevalence of AD. We found that patients could obtain a good clinical benefit based on this model. In addition, we revealed 2 distinct m6A patterns and 2 distinct m6A gene patterns in AD and demonstrated their prognostic and risk assessment significance. This present work comprehensively evaluated the functions of m6A regulators in the diagnosis and subtype classification of AD. These results suggested they have potential prognostic and risk assessment significance in AD.

Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.

目的 脊髓损伤患者的比例逐年增多,给家庭及社会带来沉重负担.本文主要目的是对脊髓损伤的致病原因、发病年龄、损伤部位及损伤严重程度等多方面因素进行综合系统分析.方法 对2005—2016年在武警总医院功能神经外科住院治疗的1395例脊髓损伤患者信息进行回顾性分析,其中包括患者年龄、性别、损伤时间、损伤节段及严重程度等.结果 1395例患者中,年龄最小5个月、最大68岁;患者平均损伤年龄为(32.09±12.46)岁.性别比例为4.1:1(男:女).主要致病原因是:交通事故(45.4％)、高处坠落(27.4％)、重物砸伤(10.8％)、摔伤(6.5％)、刀刺伤(2.0％)和肿瘤(2.0％);统计发现损伤原因与损伤的脊髓节段及严重程度之间存在相关性;在损伤的病变部位与损伤的严重程度观察中,主要体现在胸段、腰段之间有明显相关性.结论 交通事故、高处坠落、重物砸伤、摔伤是最常见的脊髓损伤的致病原因.致病原因与损伤的节段、性别、损伤的严重程度等之间存在相关性,因此,以后应从多方面、多角度关注高危人群,提高防护措施,降低发病率.

BACKGROUND:Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children. METHODS:CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 107 hWJSCs) cell therapy were recruited into this study. Assessments of motor function were performed according to scales for gross motor function measurement (GMFM) and fine motor function measurement (FMFM). The measurement data obtained in the two different groups were analyzed by t-test. Univariate repeated measures analysis of variance was used to compare the data obtained at baseline and 6 or 12 months posttransplantation and met the conditions for Mauchly's sphericity test. RESULTS:The results for fifty-seven pediatric CP patients (including 35 male and 22 female patients) who completed follow-up showed that gross and fine motor functions improved after cell therapy. Interestingly, the GMFM and FMFM scores in patients who received one course of transplantation were significantly increased at 6 months after treatment. Moreover, another course of transplantation further improved gross and fine motor function in children. The scores for GMFM and FMFM were significantly higher at 6 months posttransplantation than at baseline and showed a linear upward trend. There was no gender difference in GMFM. Interestingly, there was a significant difference between male and female patients in the B and C dimensions of FMFM. These results reveal a gender-related susceptibility to stem cell therapy, especially for movement capability of the upper extremity joint and grasping ability. Similarly, in the group aged ≤3 years old, the improvement observed in dimension A (lying and rolling) of GMFM was nearly exponential and showed a quadratic trend. The results for FMFM were similar to those for GMFM. Moreover, the improvement in motor function was not age dependent. CONCLUSIONS:In this study, our data collectively reveal that CP children display sex- or age-dependent responses to hWJSC therapy; these results shed light on the clinical utility of this approach in specific populations.

目的 分析脑性瘫痪(脑瘫)患者的临床特征及产前危险因素,为其预防、早期诊断及治疗提供科学依据.方法 以武警总医院功能神经外科2012-10至2016-05收治的2100例脑瘫患者为研究对象(观察组),同时从我院产科选择等量且年龄、性别相匹配的正常产儿作为对照组.回顾性分析观察组脑瘫患者的临床特征,并比较两组在产前的差异及脑瘫形成的影响因素.结果 2100例脑瘫患者中,平均年龄(7.43±6.21)岁,男1390例(66.19％),女710例(33.81％).其中痉挛型脑瘫最常见,占74.10％(1556/2100),粗大运动功能分级系统(Gross Motor Function Classification System,GMFCS)分级Ⅱ级最为多见,占860例(40.62％).剖宫产747例(35.57％),顺产1353例(64.43％).产前危险因素分析显示观察组早产、宫内窘迫、多胎妊娠、高龄产妇、孕期感染、妊高症及子痫等因素显著高于对照组,组间差异有统计学意义(P<0.05).多因素Logistic回归分析结果显示早产、宫内窘迫、多胎、高龄产妇、妊高症及子痫为影响脑瘫发生的独立产前危险因素.结论 脑瘫是多种危险因素共同作用的结果,产前因素在脑瘫发病中起着重要的作用,其中早产、宫内窘迫、多胎妊娠、高龄产妇、妊高症及子痫为影响脑性瘫痪的独立产前危险因素,应对这些因素进行干预,加强孕妇产前检查及相关教育,做到早发现、早干预、早治疗,降低脑瘫的患病率.

Objective To analyze the relationship between the brain magnetic resonance imaging( MRI) and cerebral palsy types/risk factors. Methods Information, including age, risk factors, clinical classification and MRI findings, of 1060 hospitalized patients with cerebral palsy was reviewed. Results Among the 1060 patients, the abnormal rate of brain MRI results was 82.17％, in which periventricular leukomalacia (PVL) (27.93％), enlargement of the lateral ventricles ( 13. 11％) , brain atrophy ( 10. 85％) , delayed myelination ( 10. 28％) , and abnormal corpus callosum (10.19％) were the common types. The abnormal rate of spastic cerebral palsy was 83.65％, in which PVL, enlarge-ment of the lateral ventricles, and delayed myelination were the commen types. The abnormal rate of dyskinetic cerebral palsy was 60.98％, in which basal ganglia damage, PVL and enlargement of the lateral ventricles were the common types. The abnormal rate of ataxic cerebral palsy was 88. 57％, in which cerebellar hypoplasia and abnormal corpus callosum were the common types. The abnormal rate of mixed type was 75.90％. Proportions of PVL, enlargement of the lateral ventricles and schizencephaly were higher in prematurity patients ( all P< 0.05) . Proportions of PVL, delayed myelina-tion, and focal cerebral ischemia were higher in patients with hypoxia asphyxia ( all P<0.05) . Proportions of basal gan-glia damage and focal cerebral ischemia were higher in patients with pathologic jaundice ( both P<0.05) . Conclusion MRI has important clinical significance in children with cerebral palsy and its changes are closely related to cerebral pal-sy types and risk factors.

Objective To study the therapeutic effect of umbilical cord mesenchymal stem cell ( UC-MSC) transplantation on incomplete cervical spinal cord injury.Methods 39 patients with incomplete cervical spinal cord injury were enrolled and received 4 times of UC-MSC transplantation through the pathways of lumbar puncture.ASIA scores and the Barthel index of activities of daily liv-ing (ADL) were used to assess the motion and sensory function, musclar tention, and activities of daily living of spinal cord patients before and half a year after the transplantation.Results The patients had improvement in their motion function, sensory function, musclar tention, and activities of daily living.And the most significant improvement was motor function, the scores changed from 61 ± 22 before operation to 70 ±18 at 6 month after the transplantation.No obvious adverse reactions occurred, such as surgical site infec-tion, cerebrospinal fluid leakage and central nervous system infection, etc.15.4%of patients experienced fever in 24 hours after oper-ation, 7.7% of patients experienced low intracranial pressure and 5.1% of patients experienced flank and lower limber pain. Conclusions UC-MSC transplantation significantly improves the sensory function, motion function, function of urination and defeca-tion and perspiration in patients with incomplete cervical spinal cord injury with few adverse reactions.

The aim of this study was to investigate the effects of transplantation with umbilical cord mesenchymal stem cells in patients with sequelae of traumatic brain injury (TBI). The study hypothesis was that umbilical cord mesenchymal stem cell transplantation could safely and effectively improve neurological function in patients with sequelae of traumatic brain injury. Forty patients with sequelae of TBI were randomly assigned to the stem cell treatment group or the control group. The patients in the stem cell treatment group underwent 4 stem cell transplantations via lumbar puncture. All patients of the group were also evaluated using Fugl-Meyer Assessments (FMA) and Functional Independence Measures (FIM) before and at 6 months after the stem cell transplantation. The patients in the control group did not receive any medical treatment (i.e., neither surgery nor medical intervention), and their FMA and FIM scores were determined on the day of the visit to the clinic and at 6 months after that clinical observation. The FMA results demonstrated an improvement in upper extremity motor sub-score, lower extremity motor sub-score, sensation sub-score and balance sub-score in the stem cell transplantation group at 6 months after the transplantation (P<0.05). The FIM results also exhibited significant improvement (P<0.05) in the patient self-care sub-score, sphincter control sub-score, mobility sub-score, locomotion sub-score, communication sub-score and social cognition sub-score. The control group exhibited no improvements after 6 months (P>0.05). All in all, the study results confirmed that the umbilical cord mesenchymal stem cell transplantation improved the neurological function and self-care in patients with TBI sequels. Umbilical cord mesenchymal stem cell transplantation may be a potential treatment for patients with sequelae of TBI. Further research, including a multicenter and large sample size prospective randomized clinical trial, will be required to define definitively the role of umbilical cord mesenchymal stem cell transplantation on sequelae of TBI.