Cardiovascular diseases， a group of major non-infectious diseases， are characterized by high morbidity and mortality， significantly influencing patients' quality of life. Hence， it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death， autophagy has been demonstrated to be associated with the pathogeneses of hypertension， diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， atherosclerosis， and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine （TCM）. Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases， and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress， inflammation， and apoptosis under the regulation of autophagy， exhibiting the unique advantages of multiple targets， multiple components， and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases （such as diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， and atherosclerosis） in recent years and summarizes the research shortcomings， providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.

Cardiovascular diseases， a group of major non-infectious diseases， are characterized by high morbidity and mortality， significantly influencing patients' quality of life. Hence， it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death， autophagy has been demonstrated to be associated with the pathogeneses of hypertension， diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， atherosclerosis， and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine （TCM）. Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases， and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress， inflammation， and apoptosis under the regulation of autophagy， exhibiting the unique advantages of multiple targets， multiple components， and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases （such as diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， and atherosclerosis） in recent years and summarizes the research shortcomings， providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.

BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring,and the advantages of Chinese medicine such as many targets,wide range,rich mechanisms,and few side effects have great potential in the treatment of various diseases. OBJECTIVE:Based on the nuclear transcription factor kappa B signaling pathway,this paper systematically expounded and summarized the research progress of kaempferol,safflower yellow,baicalin,and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS:Search terms"spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids"were searched in CNKI and PubMed databases.Totally 67 articles were finally included. RESULTS AND CONCLUSION:(1)The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse,which can regulate neutrophils,microglia,astrocytes,and macrophages,and mediate the occurrence and development of inflammation after injury.(2)The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein,the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway,and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body,thereby promoting the recovery of neurological function.(3)The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury,and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury.Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors,improve the antioxidant capacity of cells,and promote the activation of immune cells,but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis.(4)Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway,how to achieve precise intervention for nervous system inflammation and injury,and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways,in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases.

BACKGROUND:Ferroptosis is an iron-dependent regulatory form of cell death characterized by iron-dependent lipid peroxidation.Long-chain acyl-coenzyme A synthase 4(ACSL4)is involved in the formation of lipid peroxidation substrates,thereby resulting in ferroptosis.Recent studies have shown that ACSL4-mediated ferroptosis plays a key role in atherosclerotic cardiovascular disease. OBJECTIVE:To summarize the structural function and regulatory mechanism of ACSL4 and its potential molecular mechanism mediating ferroptosis,and to elaborate the application of ACSL4 driving ferroptosis in atherosclerosis,ischemic stroke and myocardial infarction,in order to provide a new therapeutic strategy for the treatment of atherosclerotic cardiovascular diseases. METHODS:Relevant literature was searched in PubMed database from database inception to August 2023 using the keywords of"atherosclerosis,ferroptosis,long-chain acyl-coenzyme A synthase 4,ACSL4,glutathione peroxidase 4,ischemic stroke,myocardial infarction,endothelial cell,smooth muscle cells,foam cell."Finally,76 documents were included for review and analysis. RESULTS AND CONCLUSION:ACSL4 participates in the formation of coenzyme derivatives of polyunsaturated fatty acids and inserts them into phospholipids to provide substrates for lipid peroxidation,the core mechanism of iron death.Among the regulatory factors of ACSL4 expression,integrin α6β4,intracellular vesicular transport factor p115,and zinc lipoprotein A20 negatively regulate its expression.Meanwhile,multiple miRs down-regulate its expression by binding to 3'-UTR.On the contrary,up-regulation of ACSL4 is mostly regulated by transcription factors.ACSL4-dependent production of phospholipids containing polyunsaturated fatty acids is an essential prerequisite for lipid peroxidation and ferroptosis.Moreover,ACSL4 and glutathione peroxidase 4 are mutually dependent as positive and negative regulators of ferroptosis,and their specific mechanisms remain to be further studied.ACSL4-mediated ferroptosis is involved in the pathological mechanism of atherosclerosis,ischemic stroke,and myocardial infarction.Endothelial cell injury in atherosclerosis is closely related to ACSL4-mediated ferroptosis,but there are no reports on the involvement of ACSL4 in foam cell formation,smooth muscle cell phenotype transformation,and calcification.ACSL4 has become a research hotspot as a biomarker and potential target of ferroptosis.Targeting ACSL4 to inhibit ferroptosis may become a new direction for the treatment of atherosclerotic cardiovascular diseases.However,there are few studies on drugs inhibiting ACSL4,and further studies are needed in the future.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

BACKGROUND:In recent years,with the in-depth study of programmed cell death,new models of programmed cell death(mitophagy,ferroptosis,cuproptosis,and disulfidptosis)involved in Alzheimer's disease injury are gradually emerging and have large research space in the future. OBJECTIVE:To review the molecular mechanism of novel programmed cell death mode(mitophagy,ferroptosis,cuproptosis,and disulfidptosis),the crosstalk mechanism of novel cell death mode,and clinical transformation in Alzheimer's disease,aiming to provide a new perspective for exploring the mechanism of action and drug targets in Alzheimer's disease. METHODS:The first author used the computer to search the literature published between 1991 and 2024.101 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Programmed cell death is a necessary regulatory pathway to maintain normal cell renewal and homeostasis.Among them,new types of programmed cell death such as mitophagy,ferroptosis,cuproptosis,and disulfidptosis are hot research fields in life science.(2)Mitophagy can clear damaged mitochondria in Alzheimer's disease neurons,reduce intracellular reactive oxygen species,restore the energy metabolism and signal transduction of neurons in Alzheimer's disease,and play a crucial role in regulating the health and function of neurons.(3)Studies on ferroptosis in Alzheimer's disease have attracted much attention.It can regulate Alzheimer's disease through various ways such as cystine/glutamate,iron metabolism,and polyunsaturated fatty acids,thus affecting Aβ deposition and Tau protein phosphorylation.Recent studies have shown that natural polyphenols,Suanzoren decoction,poria acid,and vitamin E can resist ferroptosis in Alzheimer's disease.(4)Cuproptosis is a new and unique form of cell death involving copper dependence,accumulation of fatty acylated proteins,and reduction of iron-sulfur tufting proteins.Excessive copper exposure may directly interact with Aβ plaques and amyloid precursor proteins,exacerbating cognitive impairment in Alzheimer's disease.Currently,the research field of cuproptosis is emerging,and the mechanism of action has not been fully clarified.(5)Disulfidptosis,as an emerging form of programmed cell death,is caused by disulfide stress due to excessive cystine accumulation and glucose starvation,resulting in damage to the actin skeleton associated with Alzheimer's disease.(6)Various patterns of programmed cell death have a tandem mechanism in the pathogenesis of Alzheimer's disease,forming an interaction network of various programmed cell death with autophagy as the core,providing great potential for multi-level and multi-target regulation of Alzheimer's disease.The crosstalk network mechanism between autophagy,necroptosis,and pyroptosis/ferroptosis co-regulates Alzheimer's disease.(7)Cuproptosis and disulfidptosis,as a new mode of programmed death,have not been reported deeply enough in Alzheimer's disease,and further research and continuous attentions are still needed in the future.(8)Since most studies on mitophagy,ferroptosis,cuproptosis,and disulfidptosis are based on basic experiments or biogenic analysis,there is a lack of large-scale and long-term clinical research validation.Further in-depth studies are needed in the future to provide new ideas and effective strategies for the treatment of Alzheimer's disease.

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.

Objective To study the efficacy of speech training combined with Montessori education on speech problems in children after velopharyngeal insufficiency surgery.Methods A retrospective analysis of 63 cases of children who underwent velopharyngeal repair at Children's Hospital of Soochow University between January 2019 and December 2021 was conducted.Subjects were divided into three groups.A total of 21 patients who received family rehabilitation training after the operation were divided into control group A,42 patients who received regular hospital rehabilitation training after the operation were divided into group B and group C,of which 21 patients in group B received routine speech training,and 21 patients in group C received Montessori education and routine speech training.Nasal resonance status,assessment of dysarthric intelligibility,and cranially positioned lateral radi-ographs when pronouncing/i/sounds were evaluated individually before treatment and 6 months after treatment.The improvement of velopharyngeal function,nasal resonance status,and dysarthric articulation were evaluated.Results After the six-month intervention,the dysarthric speech intelligibility were significantly improved in three groups with improvement of 35.45％in group A,43.66％in group B,and 49.33％in group C,respectively(P＜0.05).The improvement rate of nasality reached 100％in the B and C group with nasality elimination rate of 70％in group B and 95.24％nasality elimination in group C,and the efficacy of the two groups was statistically signifi-cant(P＜0.05).During phonation of the/i/tone,velopharyngeal insufficiency was observed in seven patients in group B and in only one patient in group C,and the efficacy was statistically significant in both groups(P＜0.05).Conclusion Postoperative targeted speech training is necessary in patients with velopharyngeal insufficiency,and speech training combined with Montessori education can significantly improve the function of velopharyngeal clo-sure,thus achieving a good state of nasal resonance and correct articulation as early as possible.