ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

This paper reports the diagnosis and treatment of a child with eustachian hairy polyp. The patient was a female, aged 1 year and 4 months, and visited our clinic due to "intermittent purulent discharge of the left ear, nasal congestion and sleep snoring for 1 year". Preoperative endoscopic examination found white masses at the posterior part of the nasal cavity on both sides. The imaging findings showed masses with streaks and circular-like mixed signal accompanied by slightly uneven enhancement at the left eustachian duct and the posterior wall of the nasopharyngeal cavity, and soft tissue density in the left tympanic antrum. Left modified radical mastoidectomy and radical endoscopic resection surgery for nasopharyngeal tumors was performed under general anesthesia. Histopathological examination revealed polyp of the left eustachian tube hair. The patient's symptoms improved after surgery, and no tumor recurrence was found after 3 months of follow-up.
Humans ; Female ; Eustachian Tube/surgery* ; Polyps/surgery* ; Infant ; Endoscopy

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

OBJECTIVE: Pseudomonas aeruginosa( P. aeruginosa) is a prevalent pathogenic bacterium involved in meningitis; however, the virulence factors contributing to this disease remain poorly understood. METHODS: The virulence of the P. aeruginosa A584, isolated from meningitis samples, was evaluated by constructing in vitro blood-brain barrier and in vivo systemic infection models. qPCR, whole-genome sequencing, and drug efflux assays of A584 were performed to analyze the virulence factors. RESULTS: Genomic sequencing showed that A584 formed a phylogenetic cluster with the reference strains NY7610, DDRC3, Pa58, and Pa124. Its genome includes abundant virulence factors, such as hemolysin, the Type IV secretion system, and pyoverdine. A584 is a multidrug-resistant strain, and its wide-spectrum resistance is associated with enhanced drug efflux. Moreover, this strain caused significantly more severe damage to the blood-brain barrier than the standard strain, PAO1. qPCR assays further revealed the downregulation of the blood-brain barrier-associated proteins Claudin-5 and Occludin by A584. During systemic infection, A584 exhibited a higher capacity of brain colonization than PAO1 (37.1 × 10 ⁶ CFU/g brain versus 2.5 × 10 ⁶ CFU/g brain), leading to higher levels of the pro-inflammatory factors IL-1β and TNF-α. CONCLUSION This study sheds light on the virulence factors of P. aeruginosa involved in meningitis.
Pseudomonas aeruginosa/genetics* ; Virulence Factors/metabolism* ; Animals ; Virulence ; Mice ; Pseudomonas Infections/microbiology* ; Blood-Brain Barrier/microbiology* ; Humans ; Female

This paper summarized the clinical experience of using the method of “returning fire to its origin” for treatment of paroxysmal sympathetic hyperactivity （PSH）. According to the causes and clinical characteristics of PSH， the author believes that the deficiency of kidney qi， and the loss of yin and yang are the basis of the pathogenesis of PSH. Fright causes qi to be chaotic as the triggering mechanism of PSH. The key mechanism of PSH is that the deficiency yang with upper manifestation， and the fire does not return to its origin. The treatment should be nourishing yin and astringing yang， by taking modified Yinhuo Decoction （引火汤） internally， and receiving warm moxibustion as the first choice externally with selected acupoints Guanyuan （CV 4）， Mingmen （GV 4）， and bilateral Yongquan （KI 1）； For prevention， attention should be paid to take care of stomach qi， support healthy qi， and cultivate original qi.

The increasing prevalence of the aging population, and inadequate and uneven distribution of medical resources, have led to a growing demand for telemedicine services. Gait disturbance is a primary symptom of neurological disorders such as Parkinson's disease (PD). This study proposed a novel approach for the quantitative assessment and analysis of gait disturbance from two-dimensional (2D) videos captured using smartphones. The approach used a convolutional pose machine to extract human body joints and a gait phase segmentation algorithm based on node motion characteristics to identify the gait phase. Moreover, it extracted features of the upper and lower limbs. A height ratio-based spatial feature extraction method was proposed that effectively captures spatial information. The proposed method underwent validation via error analysis, correction compensation, and accuracy verification using the motion capture system. Specifically, the proposed method achieved an extracted step length error of less than 3 cm. The proposed method underwent clinical validation, recruiting 64 patients with Parkinson's disease and 46 healthy controls of the same age group. Various gait indicators were statistically analyzed using three classic classification methods, with the random forest method achieving a classification accuracy of 91%. This method provides an objective, convenient, and intelligent solution for telemedicine focused on movement disorders in neurological diseases.
Humans ; Aged ; Parkinson Disease/diagnosis* ; Aging ; Algorithms ; Gait ; Lower Extremity

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

OBJECTIVE: To investigate the effect of hydrogen gas on NOD-like receptor protein 3 (NLRP3) inflammasomes in the cerebral cortex of rats with traumatic brain injury (TBI). METHODS: 120 adult male Sprague-Dawley (SD) rates were randomly divided into 5 groups (n = 24): sham operation group (S group), TBI model group (T group), TBI+NLRP3 inhibitor MCC950 group (T+M group), TBI+hydrogen gas group (T+H group), TBI+hydrogen gas+MCC950 group (T+H+M group). TBI model was established by controlled cortical impact. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected for 14 consecutive days before TBI operation in T+M and T+H+M groups. 2% hydrogen inhalation was given for 1 hour at 1 hour and 3 hours after TBI operation in T+H and T+H+M groups. At 6 hours after TBI operation, the pericontusional cortex tissues were obtained, the content of Evans blue (EB) was detected to evaluate the permeability of the blood-brain barrier. Water content in brain tissue was detected. The cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) and the neuronal apoptosis index was calculated. The expressions of Bcl-2, Bax, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 p20 were detected by Western blotting. The levels of interleukins (IL-1β, IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the S group, the content of EB in cerebral cortex, water content in brain tissue, apoptosis index and the expressions of Bax, NLRP3, ASC, caspase-1 p20 in T group were significantly increased, the expression of Bcl-2 was down-regulated, the levels of IL-1β and IL-18 were increased [the content of EB (μg/g): 87.57±6.89 vs. 10.54±1.15, water content in brain tissues: (83.79±2.74)% vs. (74.50±1.19)%, apoptotic index: (62.66±5.33)% vs. (4.61±0.96)%, Bax/β-actin: 4.20±0.44 vs. 1, NLRP3/β-actin: 3.55±0.31 vs. 1, ASC/β-actin: 3.10±0.26 vs. 1, caspase-1 p20/β-actin: 3.28±0.24 vs. 1, Bcl-2/β-actin: 0.23±0.03 vs. 1, IL-1β (ng/g): 221.58±19.15 vs. 27.15±3.27, IL-18 (ng/g): 87.26±7.17 vs. 12.10±1.85, all P < 0.05]. Compared with the T group, the T+M, T+H and T+H+M groups had significant reductions in the content of EB and water content in brain tissue, apoptotic index of the cerebral cortex, the expressions of Bax, NLRP3, and caspase-1 p20 in the brain tissue and the levels of IL-1β and IL-18, significant increases in the expression of Bcl-2. However, there was no significant difference in ASC expression. Compared with the T+H group, the content of EB in the cerebral cortex, water content in brain tissue, and apoptotic index, and the expressions of Bax, NLRP3 and caspase-1 p20 were further down-regulated in T+H+M group, the expression of Bcl-2 was further up-regulated, the levels of IL-1β and IL-18 were further decreased [the content of EB (μg/g): 40.49±3.15 vs. 51.96±4.69, water content in brain tissue: (76.58±1.04)% vs. (78.76±1.16)%, apoptotic index: (32.22±3.44)% vs. (38.54±3.89)%, Bax/β-actin: 1.92±0.16 vs. 2.56±0.21, NLRP3/β-actin: 1.94±0.14 vs. 2.37±0.24, caspase-1 p20/β-actin: 1.97±0.17 vs. 2.31±0.19, Bcl-2/β-actin: 0.82±0.07 vs. 0.52±0.04, IL-1β (ng/g): 86.23±7.09 vs. 110.44±10.48, IL-18 (ng/g): 40.18±3.22 vs. 46.23±4.02, all P < 0.05], but there were no statistical significance in all the indicators between T+M group and T+H group. CONCLUSIONS The mechanism by which hydrogen gas alleviates TBI may be related to inhibiting NLRP3 inflammasomes in the cerebral cortex of rats.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Actins ; Interleukin-18 ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; bcl-2-Associated X Protein ; Brain Injuries, Traumatic ; Cerebral Cortex ; Caspases

INTRODUCTION: This study aimed to elucidate the cognitive profile of patients with mild cognitive impairment with Lewy bodies (MCI-LB) and to compare it to that of patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD). METHODS: Subjects older than 60 years with probable MCI-LB (n = 60) or MCI-AD (n = 60) were recruited. All patients were tested with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess their global cognitive profile. RESULTS: The MCI-AD and MCI-LB patients did not differ in total MMSE and MoCA scores. However, some sub-items in MMSE and MoCA were shown to be screening markers for differentiating MCI-LB from MCI-AD. In the visuoconstructive test, the total score and hands subitem score in the clock-drawing test were significantly lower in MCI-LB than in MCI-AD. As for the executive function, the 'animal fluency test', 'repeat digits backward test' and 'take paper by your right hand' in MMSE all showed lower scores in MCI-LB compared with MCI-AD. As for memory, 'velvet' and 'church' in MoCA and 'ball' and 'national flag' in MMSE had lower scores in MCI-AD than in MCI-LB. CONCLUSION This study presents the cognitive profile of patients with MCI-LB. In line with the literature on Dementia with Lewy bodies, our results showed lower performance on tests for visuoconstructive and executive function, whereas memory remained relatively spared in the early period.
Humans ; Cognitive Dysfunction ; Alzheimer Disease/diagnosis* ; Neuropsychological Tests ; Cognition