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.

The periodontal ligament (PDL) plays a crucial role in transmitting and dispersing occlusal force, acting as mechanoreceptor for muscle activity during chewing, as well as mediating orthodontic tooth movement. It transforms mechanical stimuli into biological signals, influencing alveolar bone remodeling. Recent research has delved deeper into the biological and mechanical aspects of PDL, emphasizing the importance of understanding its structure and mechanical properties comprehensively. This review focuses on the latest findings concerning both macro- and micro- structural aspects of the PDL, highlighting its mechanical characteristics and factors that influence them. Moreover, it explores the mechanotransduction mechanisms of PDL cells under mechanical forces. Structure-mechanics-mechanotransduction interplay in PDL has been integrated ultimately. By providing an up-to-date overview of our understanding on PDL at various scales, this study lays the foundation for further exploration into PDL-related biomechanics and mechanobiology.
Periodontal Ligament/cytology* ; Humans ; Biomechanical Phenomena ; Mechanotransduction, Cellular/physiology* ; Stress, Mechanical

Objective:To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method.Methods:Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. Results:A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. ① MR analysis showed that TMAO may increase the risk of AP [odds ratio ( OR) = 1.100, 95% confidence interval (95% CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95% CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. ② There was a positive causal relationship between plasma TMAO level and circulating monocyte count ( OR = 1.017, 95% CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. Conclusion:TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Objective Based on exosomal miRNA and their downstream pathways,we investigated the mechanisms related to the alleviation of cartilage damage in the knee damp-heat type osteoarthritis(KOA)model in rats by Si-Miao-San.Methods Damp-heat type KOA rat model was successfully established and divided into normal control group,model group,positive drug group,and low,medium and high dose groups of Si-Miao-San.The general conditions of the rats were observed daily;behavioural,imaging and histopathological methods were used to assess the effects of Si-Miao-San on pain,swelling,cartilage degeneration,subchondral bone damage and osteophyte formation in rats with damp-heat type KOA.The miRNA high-throughput sequencing technology was used to screen the differentially expressed miRNA after Si-Miao-San intervention in model rats;Western blot was used to test the expression of PI3K/Akt/mTOR pathway(downstream pathway of differentially expressed miRNA)and autophagy-related proteins in the cartilage tissues of rats in each group.Results Compared with the model group,Si-Miao-San could effectively improve the symptoms of damp-heat,mechanical pain threshold and knee joint swelling in rats with damp-heat type KOA model,and at the same time,it could reduce the cartilage damage of the knee joints of the model rats,inhibit the destruction of the subchondral bone and the formation of osteophyte,and the overall efficacy was better in the high-dose group.A total of seven differentially expressed exosomal miRNA were screened after Si-Miao-San intervention in model rats,among which the PI3K/Akt/mTOR pathway might be its key downstream pathway.Si-Miao-San significantly down-regulated the phosphorylation levels of PI3K,AKT,mTOR,and the expression level of P62 protein,and up-regulated the expression level of Beclin-1 protein.Conclusion Si-Miao-San can exert anti-KOA effects by affecting the differential expression of serum exosomal miRNA while inhibiting the PI3K/Akt/mTOR pathway and enhancing chondrocyte autophagy.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Objective Based on exosomal miRNA and their downstream pathways,we investigated the mechanisms related to the alleviation of cartilage damage in the knee damp-heat type osteoarthritis(KOA)model in rats by Si-Miao-San.Methods Damp-heat type KOA rat model was successfully established and divided into normal control group,model group,positive drug group,and low,medium and high dose groups of Si-Miao-San.The general conditions of the rats were observed daily;behavioural,imaging and histopathological methods were used to assess the effects of Si-Miao-San on pain,swelling,cartilage degeneration,subchondral bone damage and osteophyte formation in rats with damp-heat type KOA.The miRNA high-throughput sequencing technology was used to screen the differentially expressed miRNA after Si-Miao-San intervention in model rats;Western blot was used to test the expression of PI3K/Akt/mTOR pathway(downstream pathway of differentially expressed miRNA)and autophagy-related proteins in the cartilage tissues of rats in each group.Results Compared with the model group,Si-Miao-San could effectively improve the symptoms of damp-heat,mechanical pain threshold and knee joint swelling in rats with damp-heat type KOA model,and at the same time,it could reduce the cartilage damage of the knee joints of the model rats,inhibit the destruction of the subchondral bone and the formation of osteophyte,and the overall efficacy was better in the high-dose group.A total of seven differentially expressed exosomal miRNA were screened after Si-Miao-San intervention in model rats,among which the PI3K/Akt/mTOR pathway might be its key downstream pathway.Si-Miao-San significantly down-regulated the phosphorylation levels of PI3K,AKT,mTOR,and the expression level of P62 protein,and up-regulated the expression level of Beclin-1 protein.Conclusion Si-Miao-San can exert anti-KOA effects by affecting the differential expression of serum exosomal miRNA while inhibiting the PI3K/Akt/mTOR pathway and enhancing chondrocyte autophagy.

More and more evidence shows that there is a close relationship between the inflammatory state and coronary heart disease. Inflammatory state triggers the damage of vascular endothelium in the early stage of coronary heart disease and ultimately mediates the formation of atherosclerotic plaque. The mechanism of occurrence and development of heart disease is of great significance. Phlegm is a pathological product formed by the subtle imbalance of the spleen and stomach in the transportation and transformation of water and grain. It is the general summary of a series of abnormally accumulated inflammatory substances， such as low density lipoprotein， inflammatory cells， and inflammatory factors. The nature of Phlegm determines the invasiveness and turbidity of Phlegm. Phlegm invades the meridians， causing damage to the meridians and gradually accumulating， which eventually causes the local meridian damage to aggravate. This process is similar to the persistent damage of the vascular endothelium caused by inflammation. Phlegm blocks the meridians， affects the operation of Qi and blood， causes Qi stagnation and blood stasis， and finally forms the outcome of heart and blood stasis. This process is similar to the mechanism of atherosclerotic plaques formed by continuous inflammatory damage. Heart blood stasis， depression and heat， heat toxin endogenous， forming the syndrome of heat toxin stasis， which is similar to the process of atherosclerotic plaque rupture and thrombosis causing acute cardiovascular events.The formation of Phlegm is rooted in the deficiency of spleen. Based on the ''phlegm，stasis，toxin'' theory， spleen deficiency is the intrinsic pathogenesis of the inflammatory state of coronary heart disease， and the invasion of phlegm， blood stasis of heart， heat and blood stasis are the evolution of inflammatory damage of coronary heart disease. Traditional Chinese medicine differentiation and treatment is based on strengthening the spleen and nourishing Qi to treat the root and removing phlegm and blood stasis， and clearing heat and detoxifying to treat symptoms. The related Chinese medicine compounds， Chinese patent medicines， and single Chinese medicines can reduce the inflammatory indicators of coronary heart disease， thereby improving the prognosis of coronary heart disease.

Post-stroke fatigue is one of the common symptoms of stroke patients. Continuous fatigue will affect the rehabilitation of patients' limb functions, lead to the decline of daily living ability, and at the same time, make patients lack energy, lose the initiative of rehabilitation exercise, and seriously affect the quality of life and social function. This article reviews the epidemiology, clinical characteristics, evaluation scales, influencing factors, pathophysiological mechanism and treatment of post-stroke fatigue.