ObjectiveTo investigate the contamination levels of zearalenone (ZEN) in commercially available edible vegetable oils in Ningbo City and to assess its health risks to local residents. MethodsA total of 330 samples of commercially available edible vegetable oil samples (50 each of peanut oil, corn oil, and olive oil; 40 each of rapeseed oil and blended oil; 30 each of soybean oil, rice oil, and sunflower seed oil; and 10 of camellia oil) were collected in 2024. The samples were tested for ZEN using the first method specified in GB 5009.209‒2016 National Food Safety Standard―Determination of Zearalenone in Food, namely the liquid chromatography method, and the contamination status was analyzed. Additionally, combined with dietary consumption data of residents, the Monte Carlo simulation method was employed to evaluate the health risks of ZEN in edible vegetable oils. ResultsZEN was detected in 267 out of 330 samples, with a detection rate of 80.91%, and the median (P₅₀) and the 25th, 75th percentiles (P₂₅, P₇₅) of ZEN concentrations were 2.02 (0.37, 17.90) μg·kg^-1, with a maximum value of 342.00 μg·kg^-1. The ZEN detection rates in corn oil, peanut oil, and blended oil were all 100.00%. The daily average exposure (P₅₀) and daily high exposure (P₉₅) to ZEN via edible vegetable oils among Ningbo residents were 0.001 μg·kg^-1 (normalized to body weight, same below) and 0.060 μg·kg^-1, respectively. However, 1.22% of Ningbo residents had a daily ZEN exposure exceeding the tolerable daily intake (TDI) of 0.25 μg·kg^-1. The hazard quotients (HQ) for the daily average exposure (P₅₀) and daily high exposure (P₉₅) levels were 0.004 and 0.020, respectively, both substantially below 1. Nevertheless, the probability of health risk for Ningbo residents due to ZEN exposure from vegetable oil consumption remained at 1.02%. ConclusionEdible vegetable oils in Ningbo City were contaminated with ZEN, but the probability of ZEN exposure exceeding the TDI through edible vegetable oils was relatively low, and the associated health risk probability were also minimal, indicating an overall insignificant health risk.

Basilar artery pseudoaneurysm (BAPA) is an extremely rare yet life-threatening intracranial vascular lesion, characterized by insidious clinical onset and a remarkably high mortality risk upon rupture. In this case report, we describe a patient who was admitted to our department with spontaneous subarachnoid hemorrhage (SAH). Emergency digital subtraction angiography performed on admission revealed no vascular anomalies. One month after SAH onset, a comprehensive multimodal imaging evaluation ultimately confirmed the diagnosis of BAPA. Given the technical challenges in conventional management for this specific case, Traxcess-14 microguidewire-assisted endovascular electrocoagulation was performed as a last-resort therapy. Finally, follow-up imaging at 6 months demonstrated complete resolution of BAPA. Thus, we propose that Traxcess-14 microguidewire-assisted endovascular electrocoagulation may serve as a potential salvage treatment for highly selective BAPA cases in which conventional therapeutic approaches are unfeasible or have failed.

[摘 要] 目的：探讨m6A调控因子在宫颈癌预后评估、免疫微环境特征及治疗反应中的作用，构建基于m6A调控因子的预后风险模型，并分析其与免疫浸润、药物敏感性及细胞间通信的关系。方法：基于TCGA和GEO数据库中宫颈鳞癌及腺癌（CESC）转录组数据，分析22个m6A调控因子的表达与突变情况；采用LASSO‑Cox回归构建m6A相关预后风险模型，并依据风险评分将患者分为高、低风险组。利用CIBERSORT和ESTIMATE算法评估两组免疫细胞浸润及微环境特征；通过oncoPredict预测抗肿瘤药物敏感性。整合单细胞转录组数据（E-MTAB-12305），采用CellChat分析细胞间通信网络。结果：共鉴定出12个在宫颈癌中差异表达的m6A调控因子。高风险组患者总生存期缩短（P < 0.05），免疫评分降低，且对紫杉醇、氟尿嘧啶、多柔比星等抗肿瘤药物敏感性较差（IC50较高）。单细胞分析显示宫颈癌组织中细胞间通信网络发生改变，其中T细胞与内皮/上皮细胞间的相互作用可能主要由CCL5‑ACKR1和MIF‑（CD74 + CXCR4）配体‑受体介导。在临床样本中，对关键的m6A调控因子进行mRNA和蛋白水平的验证，结果显示部分调控因子在宫颈癌组织中的表达水平高于正常宫颈组织（P < 0.05）。结论：m6A调控因子特征可有效预测宫颈癌患者预后，其风险评分与肿瘤免疫浸润、药物敏感性及细胞通信密切相关，为宫颈癌的预后分层及个体化治疗提供了新的分子依据。

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To investigate the relationship between different interleukins (ILs) and gynecological tumors, including cervical cancer, endometrial cancer, and uterine leiomyoma using two-sample Mendelian randomization (MR) analysis. Methods IL and gynecological tumor data were obtained from European populations by using the IEU OpenGWAS open database. Two-sample MR analysis was applied, different interleukins were used as exposure factors, significant SNP in GWAS data were selected as instrumental variables, and the instrumental variables were independent of each other. The risk of three kinds of gynecological tumors was analyzed separately to explore the causal relationship between ILs predicted by genes and outcome indicators. The TwoSampleMR package in R language (4.3.1) software was used for statistical analysis. MR analysis was performed using inverse variance weighted, MR Egger regression, weighted median, simple mode, and weighted mode methods. Results IL-18 receptor 1 (P=0.039) and IL-24 (P=0.025) were negatively correlated with the risk of cervical cancer. IL-4 (P=0.040), IL-21 (P=0.026), and IL-37 (P=0.027) were positively correlated with the risk of endometrial cancer. IL-15 receptor subunit alpha (P=0.005) was negatively correlated with the risk of endometrial cancer. IL-17A (P=0.005) and IL-37 (P=0.018) were negatively correlated with the risk of uterine leiomyoma. IL-21 (P=0.035) was positively correlated with the risk of uterine leiomyoma. Conclusion Genetically predicted IL-4, IL-15Rα, IL-17A, IL-18R1, IL-21, IL-24, and IL-37 are causally associated with the risk of three gynecological tumors. Further exploration of the molecular mechanism of ILs in gynecological tumors may provide potential therapeutic targets for the treatment of gynecological tumors.

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

Objective To explore the functional mechanism of spinal cord fragile X mental retardation protein(FMRP)involved in neuropathic pain(NP)by using the sciatic nerve model of chronic compression injury(CCI).Methods First,to investigate the changes of spinal cord FMRP and β-catenin following the development of NP,this study compared the 50%mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)in CCI rats,as well as changes of FMRP and β-catenin in the spinal dorsal horn post-surgery,through random grouping.Immunofluorescence staining was performed on spinal cord tissue sections from CCI rats.Second,to further validate the alterations in pain behavior when the FMRP function was lost,we measured the 50%MWT,TWL,and FMRP and β-catenin in the spinal dorsal horn after FMRP knockdown in CCI rats.Finally,we measured the 50%MWT,TWL,and FMRP and β-catenin in the case of FMRP hyperfunction for validation.Results Compared with the baseline CCI group and the naive and sham groups after modeling,the CCI group after modeling showed decreases in 50%MWT and TWL(all P<0.001).After modeling,compared with the naive group and the sham group,the CCI group presented up-regulated expression of FMRP(P=0.027,P=0.022)and β-catenin(P<0.001,P=0.001)in the spinal dorsal horn.No co-localization of FMRP with astrocytes and microglia was observed in the spinal cord,while the co-localization with neurons was observed.Compared with the baseline,the CCI+FMRP knockdown group showed decreases in 50%MWT(P=0.015)and TWL(P=0.001)after modeling.After intrathecal injection of small interfering RNA(siRNA),the 50%MWT(P=0.020)and TWL(P=0.009)of the CCI+FMRP knockdown group were increased.Moreover,compared with the CCI group and the CCI+solvent group,the CCI+FMRP knockdown group showed increases in 50%MWT(both P<0.001)and TWL(P=0.005,P=0.006).After intrathecal injection of siRNA,the expression levels of FMRP(P=0.012,P=0.007)and β-catenin(both P<0.001)in the spinal dorsal horn of the CCI+FMRP knockdown group were lower than those of the CCI group and the CCI+solvent group.Compared with the baseline FMRP overexpression group and the naive and negative control groups after adeno-associated virus(AAV)injection,the FMRP overexpression group after AAV injection showed decreases in 50%MWT and TWL(all P<0.001).After AAV injection,compared with the naive group and the negative control group,the FMRP overexpression group demonstrated up-regulated expression of FMRP(both P<0.001)and β-catenin(P=0.006,P=0.008)in the spinal cord.Conclusions This study confirms that spinal cord FMRP and β-catenin are involved in NP induced by CCI.Spinal cord FMRP may be one of the potential therapeutic targets for NP.
Animals ; beta Catenin/metabolism* ; Neuralgia/metabolism* ; Fragile X Mental Retardation Protein/physiology* ; Spinal Cord/metabolism* ; Rats ; Rats, Sprague-Dawley ; Male

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

OBJECTIVE: To review the clinical applications of functional perforator flaps in restoring human body functions. METHODS: An extensive literature review was conducted on both domestic and international publications to summarize the clinical use of functional perforator flaps for functional restoration. RESULTS: Perforator flaps are among the most commonly used flaps in reconstructive surgery. Beyond providing soft tissue repair, they are increasingly employed to reconstruct diverse bodily functions, leading us to propose the concept of the "functional perforator flap". Although various forms of functional perforator flaps are currently utilized, reports are predominantly scattered case studies, lacking systematic organization. Commonly used functional perforator flaps can be categorized into five types: chimeric perforator flaps, perforator flaps for nerve function restoration, perforator flaps for lymphatic drainage enhancement, flow-through perforator flaps, and perforator flaps for restoring bone and joint motion. These flaps significantly broaden the application scope of perforator flaps, elevating the goal of reconstruction from mere wound repair to achieving repair concurrent with functional reconstruction. CONCLUSION The application of various functional perforator flap designs significantly improves wound reconstruction outcomes and represents an effective approach for managing complex defects. Future developments will undoubtedly see more forms of functional perforator flaps reported to meet increasingly sophisticated reconstructive demands.
Humans ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Soft Tissue Injuries/surgery* ; Skin Transplantation/methods* ; Wound Healing