Abnormal synaptic plasticity is an early pathological feature of Alzheimer disease (AD). Synaptic damage and dysfunction initiate neuronal degeneration and death, ultimately leading to cognitive impairment. Traditional Chinese medicine (TCM) can effectively ameliorate cognitive dysfunction through multitarget regulation of synaptic plasticity. This review summarizes the mechanisms by which TCM, including active components, single herbs, and classical formulas, modulates synaptic plasticity, offering new insights for future research and clinical applications. Relevant experimental studies published between 2020 and 2024 were retrieved from major databases, including China National Knowledge Infrastructure, the National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and Web of Science. Network pharmacology and bioinformatics approaches were used to predict the therapeutic effects and mechanisms of TCM on AD-related synaptic plasticity. In total, 15 TCM single herbs and 11 TCM formulas were identified as enhancing AD-related synaptic plasticity. Additionally, 15 active ingredients targeting synaptic plasticity in AD were retrieved from TCM databases over the past decade. This review provides novel perspectives and strategic directions for future AD research and therapeutic development.

In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe²⁺ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe²⁺ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
Ferroptosis/drug effects* ; Dental Pulp/drug effects* ; Animals ; Pulpitis/pathology* ; Rats ; Thymalfasin/pharmacology* ; Humans ; Male ; Thymosin/pharmacology* ; Disease Models, Animal ; Rats, Sprague-Dawley

OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective:To explore the clinical utility of peripheral immune-inflammatory markers in predicting late-life depression with cognitive impairment(LLD+ CI + ). Methods:A cross-sectional study was conducted between January 2020 and December 2021, collecting demographic data, peripheral blood inflammatory markers, and cognitive function scores from 40 patients with LLD+ CI + , 38 patients with late-life depression without cognitive impairment(LLD+ CI -), and 26 healthy controls(HCs). Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were employed to assess the value of peripheral blood inflammatory markers in differentiating LLD+ CI + . Results:Patients with LLD+ CI + exhibited significantly different levels of lymphocytes, C-reactive protein(CRP), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio(NHR), and neutrophil-to-lymphocyte ratio (NLR)compared with the LLD+ CI - group and the HGs group( F=4.000, 11.642, 13.541, 10.441, 6.623, 4.193; P=0.022, 0.003, 0.001, 0.005, 0.036, 0.018). The multivariate logistic regression analysis of factors influencing LLD+ CI + revealed that elevated levels of CRP( OR=4.933, 95% CI: 1.385-17.563, P=0.014), SII( OR=5.534, 95% CI: 1.336-22.927, P=0.018), and NLR( OR=3.386, 95% CI: 1.470-7.797, P=0.004)constitute risk factors for geriatric depression with cognitive impairment, while an increased lymphocyte count( OR=0.206, 95% CI: 0.058-0.725, P=0.014)serves as a protective factor.Further analysis identified CRP, lymphocytes, SII, and NLR as significant predictors for LLD+ CI + , with areas under the curve (AUC) values of 0.849(95% CI: 0.760-0.934), 0.847(95% CI: 0.761-0.933), 0.860(95% CI: 0.777-0.943), and 0.857(95% CI: 0.777-0.938), respectively, in distinguishing LLD with or without cognitive impairment. Conclusions:Peripheral immune-inflammatory markers represent an economical and effective approach for investigating the pathophysiological changes and predictive factors associated with LLD+ CI + .These findings provide valuable insights into the underlying mechanisms and potential therapeutic avenues.

Malignant tumors(commonly referred to as cancer)represent a major global public health challenge and contribute significantly to the worldwide disease burden.Early screening plays a critical role in improving detection rates,enabling timely intervention,and enhancing pa-tient survival rates.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifical-ly rational,multi-cancer screening approach offers several advantages:it optimizes the use of bio-logical samples,reduces time costs for participants,enhances the efficiency and comprehensive-ness of screening,and minimizes overall expenses.Such an approach also facilitates the rational allocation of healthcare resources,ultimately helping to reduce the societal burden of cancer.To address this need,the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China.This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and interna-tional researches on cancer screening,early detection,and treatment for prevalent malignancies.Drawing upon China's unique demographic and healthcare context,as well as practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the principles and methodologies established by the World Health Organization(WHO),aiming to:enhance the effectiveness of combined cancer screening in China,improve early detec-tion rates,and provide a scientific foundation for national cancer prevention and control strategies.

Malignant tumors(commonly referred to as cancers)represent a major global public health challenge and contribute substan-tially to the global disease burden.Early screening plays a crucial role in improving detection rates,enabling timely intervention,and enhan-cing patient survival.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifically rational,multi-cancer screening approach offers several advantages:it optimizes the use of biological samples,reduces the time burden for participants,enhances the efficiency and comprehensiveness of screening,and min-imizes overall expenses.Moreover,this approach facilitates rational allocation of healthcare resources,ultimately helping to reduce the soci-etal burden of cancer.To address gap,the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers.This consensus integrates multidisciplinary expertise and synthesizes the latest do-mestic and international researches on cancer screening,early detection,and treatment of prevalent malignancies.Drawing upon China's unique demographic and healthcare context and practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the prin-ciples and methodologies established by the World Health Organization(WHO),aiming to enhance the effectiveness of combined cancer screening in China,improve early detection rates,and provide a scientific foundation for national cancer prevention and control strategies.

Objective:To compare the effect of transcranial magnetic stimulation (rTMS) of the contralesional hemisphere at different frequencies on the recovery of upper limb motor function after a moderate-to-severe ischemic stroke.Methods:The inter-hemisphere compensation model was applied along with electroencephalogram (EEG) power spectrum density measurements. Thirty stroke survivors were randomly assigned to a sham stimulation group ( n=9), a high-frequency stimulation group ( n=11) or a low-frequency stimulation group ( n=10). In addition to physical and pharmacological therapy, the low-frequency and high-frequency groups received 1Hz or 5Hz rTMS, while the sham group received sham stimulation. The rTMS was delivered over the contralesional (unaffected) hemisphere once daily for 20 minutes over 15 consecutive days. Before, as well as 7 and 15 days after the treatment, all of the subjects′ motor functioning was assessed using the Fugl-Meyer Assessment for the upper extremity (FMA-UE) and their ability in the activities of daily living was assessed using the modified Barthel Index (MBI). Resting-state EEGs with the eyes closed were also recorded, and absolute alpha power across the whole brain was calculated. Changes from baseline FMA-UE and MBI scores and absolute alpha power were analyzed using one-way and repeated-measures analysis of variance. Results:After the treatment, significant within-group improvements from baseline were observed in the FMA-UE scores, MBIs and absolute alpha power, except for absolute alpha power in the low-frequency and sham groups. The repeated-measures analysis of variance revealed significant time × group interactions for FMA-UE ( F=9.926, P≤0.001), MBI ( F=8.789, P≤0.001) and absolute alpha power ( F=4.511, P≤0.05). So the treatment effects varied among the groups. Post hoc Bonferroni-corrected comparisons showed that the high-frequency group exhibited significantly greater improvements from baseline in terms of all three indicators compared with the other two groups. Conclusions:High-frequency (5Hz) rTMS applied to the contralesional hemisphere produced greater improvement than low-frequency (1Hz) stimulation in the upper limb motor function of patients with moderate-to-severe stroke. These findings support the use of the interhemispheric compensation model to guide rTMS therapy, particularly for patients with FMA-UE scores below 43.

Objective To explore the effects of mental fatigue on attention maintenance function by electroencephalogram(EEG)signal characteristics and cortical source analysis.Methods A total of 25 healthy males were recruited as subjects and contingent negative variation(CNV)auditory paradigm was used to assess the differences in EEG characteristics before and after mental fatigue,with the average amplitude of CNV at different processing stages as the analysis indices.Then,the 3-dimensional distribution of cortical current density changes of CNV after mental fatigue were calculated by standardized low-resolution electromagnetic tomography analysis(sLORETA).Results The reaction time of the CNV signal remained unchanged following mental fatigue(P＞0.05),while the lapse rate exhibited a significant increase(P＜0.05).Besides,mental fatigue was related to a notable decrease in the amplitude of CNV early components(500-1 000 ms after warning stimulus)at the central and central parietal electrodes,and a significant reduction in the amplitude of CNV late components(2 550-3 050 ms after warning stimulus)at the prefrontal,frontal,central,and central parietal electrodes(all P＜0.05).The results of sLORETA source analysis showed that the brain activity in the left posterior insular cortex decreased after mental fatigue during the late component of CNV(P＜0.05).Conclusion The decreased activation of the posterior insula,which plays a crucial role in sensorimotor information integration,could potentially serve as a neural mechanism for the reduction of CNV amplitude and the impairment of attention maintenance function following mental fatigue.