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.

ObjectiveTo investigate whether the effect of Danggui Shaoyaosan （DSS） on cognitive impairment is related to its promotion of ketone body metabolism in the brain and regulation of glutamate/α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor （AMPAR） pathway. MethodsMale APP/PS1 mice were randomized into model， low-dose （3.2 g·kg^-1） DSS， medium-dose （6.4 g·kg^-1） DSS， high-dose （12.8 g·kg^-1） DSS， ketogenic diet， and inhibitor （talampanel， 5 mg·kg^-1） groups. C57BL/6J wild-type mice were selected as the normal group. The talampanel group was intragastrically administered for 2 consecutive weeks from the 6th week， and the other groups were continuously treated for 8 weeks before behavioral testing. The ultrastructure of synapses in hippocampal CA1 region was observed by transmission electron microscopy， and calcium/calmodulin-dependent kinase Ⅱ （CaMKⅡ） expression was detected by immunohistochemistry （IHC）. The levels of β-hydroxybutyrate （BHB） and lactic acid （LAC） were measured by biochemical kits， and those of glutamate （Glu）， glutamine （Gln）， γ-aminobutyric acid （GABA）， and synaptophysin （SYP） by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of glutamine synthetase （GS）， glutaminase （GLS）， glutamate decarboxylase （GAD）， CaMKⅡ， and AMPAR subunits GluA1 and GluA2 were quantified by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of GS， GLS， GAD， GluA1， and GluA2 by Western blot. ResultsCompared with the normal group， the model group exhibited decreased recognition index， spontaneous alternation rate， and residence time in the target quadrant （P<0.01）， increased escape latency and ratio of the time in the opposite side of the target quadrant to the time in the target quadrant （P<0.05， P<0.01）， damaged synaptic ultrastructure of hippocampal CA1 region， increased positive expression of CaMKⅡ， no significant difference in BHB level， elevated LAC and Glu levels （P<0.01）， declined SYP， Gln， and GABA levels （P<0.01）， downregulated mRNA and protein levels of GS， GAD， and GluA2 （P<0.05， P<0.01）， and upregulated mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and mRNA level of CaMKⅡ （P<0.01）. Compared with the model group， DSS intervention improved the behavioral indexes of mice （P<0.05， P<0.01）， enhanced the synaptic ultrastructure plasticity in hippocampal CA1 region， decreased the positive expression of CaMKⅡ， raised the BHB level （P<0.01）， reduced the LAC and Glu levels （P<0.01）， elevated the SYP， Gln， and GABA levels （P<0.01）， upregulated the mRNA and protein levels of GS， GAD， and GluA2， and downregulated the mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and the mRNA level of CaMKⅡ （P<0.01）. ConclusionDSS can improve the learning and memory and enhance the synaptic plasticity of APP/PS1 mice. Its neuroprotective effect is coupled with the promotion of ketone body formation and remodeling of brain energy metabolism， and is related to the regulation of glutamate/AMPAR pathway.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

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.

Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

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

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 patient 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 scientifically rational, multi-cancer screening approach offers several advantages: it optimizes the use of biological samples, reduces time costs for participants, enhances the efficiency and comprehensiveness 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 international 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 detection rates, and provide a scientific foundation for national cancer prevention and control strategies.

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