BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

Mitochondrial autophagy is an important mechanism for maintaining cellular homeostasis,closely related to the occurrence and development of cerebral ischemic injury,and is an important way of neuronal death.In recent years,a large number of experimental studies have confirmed that traditional Chinese medicine has a significant effect on treating cerebral ischemic injury.Its advantages of multi-target,multi pathway,low toxicity and high efficiency have become an important component of the treatment of cerebral ischemic injury.Traditional Chinese medicine formulas and monomeric active ingredients such as Xiaoxuming decoction,Zishen Huoxue formula,flavonoids,alkaloids,etc.can regulate mitochondrial autophagy related signaling pathways and targets,inhibit neuronal autophagic death,alleviate pathological damage to brain tissue,and exert neuroprotective effects.This article analyzes the molecular mechanism of traditional Chinese medicine regulating mitochondrial autophagy in the treatment of cerebral ischemic injury from four aspects:an overview of mitochondrial autophagy,related signaling pathways,its relationship with cerebral ischemic injury,and the regulatory effects of traditional Chinese medicine.The aim is to provide ideas and references for future basic research and clinical treatment.

Objective To investigate the effect and mechanism of melatonin in alleviating hypoxia-induced apoptosis in ovarian gra-nulosa cells.Methods Rat ovarian granulosa cells were isolated and divided into normoxic,hypoxic,and melatonin groups.Hypoxia-induced injury models were established in the hypoxic and melatonin groups,and granulosa cells in the melatonin group were treated with melatonin.A total of 24 rats were randomized into the control,model,and intervention groups(n=8 per group).Rat models of declining ovarian function induced by long-term hypoxia were established in the model and intervention groups.The rats in the intervention group were intraperitoneally injected with melatonin.Cell proliferation was measured using a CCK-8 assay,and lactate secretion and HIF-1αprotein with a specific kit,respectively.The levels of estradiol and progesterone in the cell supernatant and rat serum were detected using ELISA.Granulosa cell apoptosis was detected by flow cytometry,ovarian morphology by HE staining,and Bax and caspase-3 expression by Western blotting.Results Compared with the normoxic group,the hypoxic group exhibited decreased granulosa cell proliferation,increased apoptosis,elevated lactate and HIF-1α levels,and reduced estradiol and progesterone levels(P＜0.05).Compared with hypoxic group,these changes were significantly reversed in the molatonin group(P＜0.05).Compared with the control group,the model group showed increased lactate,HIF-1α,Bax,and caspase-3 levels,decreased estradiol and progesterone levels,and reduced follicles.Compared with the model group,all the indicators were ameliorated in the intervention group(P＜0.05).Conclusion Melatonin alleviated hypoxia-induced granulosa cell apoptosis and promoted the recovery of ovarian function.

BACKGROUND:Research has shown that endoplasmic reticulum stress-induced autophagy of neurons in the ischemic penumbra is a key link in cerebral ischemia-reperfusion injury.Autophagy mediated by the dissociation and activation of endoplasmic reticulum transmembrane proteins PERK,IRE1 α,ATF6,and GRP78/BIP plays an important role in neuronal outcomes.Traditional Chinese medicine can regulate endoplasmic reticulum stress-autophagy,reduce neuronal damage or death,and exert neuroprotective effects.OBJECTIVE:To explore the role of endoplasmic reticulum stress-autophagy in cerebral ischemia-reperfusion injury and the research progress in the regulatory mechanisms of traditional Chinese medicine.METHODS:A literature retrieval was conducted in CNKI and PubMed for relevant literature related to endoplasmic reticulum stress,autophagy,cerebral ischemia-reperfusion injury,and regulation by traditional Chinese Medicine published from January 2015 to May 2024.The search terms were"cerebral ischemia-reperfusion injury,ischemic stroke,brain injury,endoplasmic reticulum stress,autophagy,traditional Chinese medicine,compounds,signaling pathways,saponins,polyphenols,alkaloids"in Chinese and English,respectively.Any literature that is inconsistent with the research content,outdated,or duplicated was excluded.A total of 1197 relevant literature were retrieved,and 71 articles were ultimately included.RESULTS AND CONCLUSION:(1)Numerous studies have suggested that endoplasmic reticulum stress-autophagy is closely related with cerebral ischemia-reperfusion injury.(2)The active ingredients and compound formulas of traditional Chinese medicine monomers can regulate the expression of endoplasmic reticulum stress-autophagy related proteins,alleviate neuronal damage,and exert neuroprotective effects by regulating signal pathways such as PERK-eIF2α-ATF4,IRE1α-ASK1-JNK,and IRE1α-XBP.

Mitochondrial autophagy is an important mechanism for maintaining cellular homeostasis,closely related to the occurrence and development of cerebral ischemic injury,and is an important way of neuronal death.In recent years,a large number of experimental studies have confirmed that traditional Chinese medicine has a significant effect on treating cerebral ischemic injury.Its advantages of multi-target,multi pathway,low toxicity and high efficiency have become an important component of the treatment of cerebral ischemic injury.Traditional Chinese medicine formulas and monomeric active ingredients such as Xiaoxuming decoction,Zishen Huoxue formula,flavonoids,alkaloids,etc.can regulate mitochondrial autophagy related signaling pathways and targets,inhibit neuronal autophagic death,alleviate pathological damage to brain tissue,and exert neuroprotective effects.This article analyzes the molecular mechanism of traditional Chinese medicine regulating mitochondrial autophagy in the treatment of cerebral ischemic injury from four aspects:an overview of mitochondrial autophagy,related signaling pathways,its relationship with cerebral ischemic injury,and the regulatory effects of traditional Chinese medicine.The aim is to provide ideas and references for future basic research and clinical treatment.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.

BACKGROUND:Ferroptosis is a programmed cell death mode regulated by iron dependent lipid peroxidation,closely related to the occurrence,development,and outcome of ischemic brain injury.With the continuous deepening of research on ferroptosis in recent years,it has been found that Chinese herbal compounds and monomers can regulate ferroptosis by reducing iron overload,reducing the production of reactive oxygen species,and regulating lipid synthesis,to alleviate cerebral ischemic injury and promote neurological function recovery.OBJECTIVE:To explore the relationship between ferroptosis and ischemic brain injury,and the mechanism by which traditional Chinese medicine regulates ferroptosis in the treatment of ischemic brain injury.METHODS:Literature on ferroptosis and ischemic brain injury and the regulatory mechanism of traditional Chinese medicine published from January 2018 to May 2024 was searched in CNKI and PubMed databases.The search terms were"iron death,ischemic stroke,brain injury,reactive oxygen species,lipid metabolism,traditional Chinese medicine formulas,terpenes,flavonoids,phenols,alkaloids,phthalides"in Chinese and English,respectively.Irrelevant,duplicated or outdated literature was excluded.A total of 1 526 relevant literature were retrieved,and 87 articles were ultimately included.RESULTS AND CONCLUSION:Numerous experimental studies have confirmed that ferroptosis plays an important role in ischemic brain injury.Chinese medicine prescriptions can regulate ferroptosis through various approaches,for examples:total saponins of Panax notoginseng can regulate iron metabolism and inhibit lipid peroxidation;carvacrol inhibits neuronal ferroptosis by increasing glutathione peroxidase 4 expression;Chinese herbal compounds and monomeric active ingredients can regulate ferroptosis-related pathways,such as glutathione/glutathione peroxidase 4(GPX4),nuclear factor E2-related factor 2(Nrf2)/hemoglobin oxygenase 1(HO-1),ferric death inhibitory protein 1(FSP1)/CoQ10 and guanosine triphosphate cyclohydrolase 1(GCH1)/tetrahydrobiopterin(BH4),to reduce neuronal damage and death,and exert neuroprotective effects.

BACKGROUND:Research has shown that endoplasmic reticulum stress-induced autophagy of neurons in the ischemic penumbra is a key link in cerebral ischemia-reperfusion injury.Autophagy mediated by the dissociation and activation of endoplasmic reticulum transmembrane proteins PERK,IRE1 α,ATF6,and GRP78/BIP plays an important role in neuronal outcomes.Traditional Chinese medicine can regulate endoplasmic reticulum stress-autophagy,reduce neuronal damage or death,and exert neuroprotective effects.OBJECTIVE:To explore the role of endoplasmic reticulum stress-autophagy in cerebral ischemia-reperfusion injury and the research progress in the regulatory mechanisms of traditional Chinese medicine.METHODS:A literature retrieval was conducted in CNKI and PubMed for relevant literature related to endoplasmic reticulum stress,autophagy,cerebral ischemia-reperfusion injury,and regulation by traditional Chinese Medicine published from January 2015 to May 2024.The search terms were"cerebral ischemia-reperfusion injury,ischemic stroke,brain injury,endoplasmic reticulum stress,autophagy,traditional Chinese medicine,compounds,signaling pathways,saponins,polyphenols,alkaloids"in Chinese and English,respectively.Any literature that is inconsistent with the research content,outdated,or duplicated was excluded.A total of 1197 relevant literature were retrieved,and 71 articles were ultimately included.RESULTS AND CONCLUSION:(1)Numerous studies have suggested that endoplasmic reticulum stress-autophagy is closely related with cerebral ischemia-reperfusion injury.(2)The active ingredients and compound formulas of traditional Chinese medicine monomers can regulate the expression of endoplasmic reticulum stress-autophagy related proteins,alleviate neuronal damage,and exert neuroprotective effects by regulating signal pathways such as PERK-eIF2α-ATF4,IRE1α-ASK1-JNK,and IRE1α-XBP.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.