Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

Objective:To estimate the radiation dose to caregivers and the public from 177Lu- peptide receptor radionuclide therapy (PRRT) for pediatric neuroblastoma patients and determine the duration of contact restrictions, in order to provide a reference for relevant radiation protection measures. Methods:A retrospective study was conducted by collecting data from 18 pediatric neuroblastoma patients, aged between 3 and 13 (6.72±2.72), who received 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) treatment at the Nuclear Medicine Department of Shandong Cancer Hospital from June 2023 to July 2023. Absorbed dose rate in air at 0, 0.1, 0.5, 1 and 2 m from the patients was measured using a radiation-survey at 1, 4, 24, 48 and 96 h after administration. The whole-body region of interest was delined using HERMES software. Subsequently, curve regression fitting was performed using a biexponential function model. By incorporating hypothesized social contact durations, the effective doses received by family members and the public in contact with patients were estimated. Additionally, MIM software was used to outline the whole-body VOI to obtain the total volume of lesions, and the Pearson or Spearman correlation coefficient was employed to analyze the relationship between the absorbed dose rate in air and clinical indicators as well as the total volume of lesions. Results:The 177Lu-DOTATATE administration dose was (4 353.42±1 451.51) MBq. All patients were discharged from hospital 24 h after 177Lu-DOTATATE administration. At the time of discharge, patients had excreted (76.70±3.99)% of the administered activity, and the absorbed dose rate in air at 0.1, 1 and 2 m from the patients were (32.74±6.98), 3.68(3.01, 4.70) and (1.22±0.51) μSv/h, respectively. After being discharged, the radiation doses to caregivers from children aged 2-5 years and 5-13 years were (2.47±1.80) mSv and (0.88±0.47) mSv, respectively. The contact restriction duration was 2 d for nighttime sleeping with family members and 1 d for contact with other children. On the day of discharge, patients should limit their time on public transportation within 4 h and do not need to restrict private transportation. Conclusions:To ensure the effective dose kept within the safety limits stipulated by current regulations, it is necessary to implement contact restrictions for patients’ family members and the public. After implementing preventive measures, 177Lu-DOTATATE treatment is a safe radionuclide therapeutic option.

Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease, which has become the leading cause of dementia in the elderly. In recent years, non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation, transcranial electrical stimulation, focused ultrasound stimulation and transcranial photobiomodulation, has been widely used in AD treatment. Although NIBS can improve the clinical symptoms of AD patients, its efficacy is still controversial. This article reviews the latest research progress in role of NIBS in AD so as to provide reference for clinical workers.

Objective:To construct a framework for evaluating the quality of health economic evaluation methodology based on the pragmatic clinical trial.Methods:An evaluation framework was constructed based on existing quality evaluation tools for health economic evaluation other quality evaluation tools.The weights of each item in the framework were determined by the Delphi method,and the weighted average was calculated using the expert authority coefficient.Results:A total of 23 experts were consulted,and the expert authority coefficients were 0.88 and 0.90,respectively.The results of the Wilcoxon signed-rank test showed no statistically signifi-cant differences among the expert opinions in two rounds(P＞0.05).Finally,a framework with 3 dimensions and 8 items was estab-lished.Conclusion:The evaluation framework has high scientificity and reliability.

Objective To investigate the functional changes of oligodendrocytes in a mouse model of cognitive impairment induced by microwave radiation and the mechanism.Methods C57BL/6N male mice were exposed to S-band microwave at 2.856 GHz and 8 mW/cm2 for 15 min.The rectal temperature of mice was monitored by an optical fiber thermometer during microwave radiation.The changes of autonomous exploration behavior and learning and memory ability of mice on the 1st and 7th days after microwave radiation were detected via the open field test and novel object recognition test.Immunofluorescence was used to detect the expression and distribution of neuroglia-2 proteoglycan(NG2)and myelin basic protein(MBP)in the hippocampus of mice on the 1st and 7th days after radiation.Clemastine fumarate,a drug that promoted the maturation of oligodendrocyte precursor cells was administered by gavage,and the expression levels of brain-derived neurotrophic factor(BDNF)and fibroblast growth factor 2(FGF2)in hippocampal tissues were detected by radioimmunoassay at 1 and 7 days after radiation.The changes of myelin sheath structure an 1 and 7 days after radiation were observed by transmission electron microscopy.The effects of clemastine fumarate on learning and memory impairment induced by microwave exposure in mice were assessed via open field and new object recognition experiments.Results Under the experimental conditions,the rectal temperature in mice caused by microwave radiation increased by less than 1 ℃,which was within the thermal safety range of the body.The open field test showed that compared with the control group,the microwave radiation group didn't change significant in terms of movement speedon the 1st and 7th days,but the time spent exploring in the central area was significantly reducedon the 1st day after radiation(P＜0.05).In the novel object recognition test,the indexes of the mice on the 1st day were significantly reduced(P＜0.05),indicating that the anxiety like behavior and cognitive function of the mice were impaired after microwave radiation.Compared with the control group,the proportion of NG2+area in the hippocampus was significantly decreased(P＜0.05)in the microwave radiation group,while that of MBP+area hardly changed on the 1st day after microwave radiation(P＞0.05).The expression level of oligodendrocyte related BDNF in the hippocampus was significantly decreased(P＜0.05).The myelin of the corpus callosum was broken,and the myelin g ratio was significantly increased(P＜0.05),suggesting that micro wave radiation could reduce the number of oligodendrocyte precursors and damage the secretion and myelin function of oligodendrocyte.Compared with the radiation group,the expression levels of BNDF and FGF2 in the radiation combined with clemastine fumarate group were up-regulated,the myelin g ratio was significantly decreased on the 1st day after radiation(P＜0.05),and the novel object recognition index was significantly increased(P＜0.05).Conclusion Pulsed microwave radiation below the body's fever threshold can cause cognitive dysfunction and other brain damage in mice.The impaired secretion and myelin function of oligodendrocytes and the decreased self-repair ability are the important mechanisms of cognitive dysfunction induced by microwave radiation.

Due to their good properties of elastic modulus, degradability and ability to promote bone repair, magnesium alloys have become a research hotspot in research of orthopedic implants. Nevertheless, most of the biomedical magnesium alloys currently available fail to meet the requirements in orthopedics because of their rapid degradation after implantation. Rare earth-magnesium alloys possess excellent corrosion resistance and are expected to become important materials as clinical orthopedic implants. This review summarizes the recent progress in studies of the physiological functions of rare earth elements, the effects of supplementation of rare earth elements on biomechanical properties and the in vitro and in vivo biocompatibility of magnesium alloys, and their contribution to tendon-bone healing, addressing also the current clinical orthopedic applications of different rare earth-magnesium alloys, challenges, and future strategies for improving these alloys.
Alloys/chemistry* ; Magnesium/chemistry* ; Metals, Rare Earth/chemistry* ; Humans ; Biocompatible Materials ; Prostheses and Implants

Closed-loop neuromodulation, especially using the phase of the electroencephalography (EEG) rhythm to assess the real-time brain state and optimize the brain stimulation process, is becoming a hot research topic. Because the EEG signal is non-stationary, the commonly used EEG phase-based prediction methods have large variances, which may reduce the accuracy of the phase prediction. In this study, we proposed a machine learning-based EEG phase prediction network, which we call EEG phase prediction network (EPN), to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data. We verified the performance of EPN on pre-recorded data, simulated EEG data, and a real-time experiment. Compared with widely used state-of-the-art models (optimized multi-layer filter architecture, auto-regress, and educated temporal prediction), EPN achieved the lowest variance and the greatest accuracy. Thus, the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Machine Learning ; Signal Processing, Computer-Assisted ; Male ; Adult ; Neural Networks, Computer ; Brain Waves/physiology*

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective To investigate the effects of a 100 mT static magnetic field(SMF)on emotional behavior and brain damage-related molecules in mice.Methods Fifty-eight C57BL/6N mice were randomly divided into control group(n=25)and observation group(n=33).Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days,while mice in control group underwent pseudo-exposure.On the 7 and 14 days of exposure,anxiety-like behavior was assessed using open field and elevated plus maze tests.Cerebral blood flow was monitored using laser speckle imaging,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4,central nervous system specific protein β(S100β),neuron-specific enolase(NSE),and brain-derived neurotrophic factor(BDNF)were measured by radioimmunoassay.BDNF expression in the brain was detected by immunofluorescence.Results On the 7 and 14 days of SMF exposure,the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies,durations,and distance entering the central area of the open field and the open arm of the elevated plus maze(P>0.05).Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period(P>0.05).The results of radioimmunoassay showed that compared with control group,on the 7 d of SMF exposure,the serum IL-1β,NSE and S100β levels were significantly increased(P<0.05),the serum BDNF level was significantly decreased(P<0.05),and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group(P<0.01).On the 14 d of SMF exposure,serum IL-1β,TNF-α,NSE,and S100β levels were significantly increased(P<0.05,P<0.0001),and the brain IL-1β and TNF-α levels were significantly increased(P<0.01)in observation group.No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups(P>0.05).Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice,without inducing anxiety-like behavior.