Sarcopenia is a systemic disease characterized by accelerated loss of skeletal muscle mass and function,leading to an increased incidence of adverse outcomes such as falls and fractures.Sarcopenia is classified into primary and secondary types,with primary sarcopenia being closely related to aging and posing a serious threat to a healthy life among the elderly.Sarcopenia has an insidious onset and is often overlooked in terms of its clinical treatment.Its pathogenesis is complex,involving functional changes and pathological alterations in multiple systems,and presenting major research challenges.Cell models can effectively be used to simulate the pathological changes of diseases under controllable conditions,thus facilitating the investigation of the etiology and factors influencing sarcopenia,and providing an important approach for in-depth studies of its mechanism;however,there is currently no standardized cell model in the field of sarcopenia research.Commonly used cell models currently include models involving protein metabolism interventions,oxidative stress,and inflammatory response interventions.This review considers the commonly used skeletal muscle cell types and modeling method of sarcopenia,to provide a solid foundation and important method ological reference for further simulation of the pathological process of sarcopenia in subsequent experimental studies.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

Sarcopenia is a systemic disease characterized by accelerated loss of skeletal muscle mass and function,leading to an increased incidence of adverse outcomes such as falls and fractures.Sarcopenia is classified into primary and secondary types,with primary sarcopenia being closely related to aging and posing a serious threat to a healthy life among the elderly.Sarcopenia has an insidious onset and is often overlooked in terms of its clinical treatment.Its pathogenesis is complex,involving functional changes and pathological alterations in multiple systems,and presenting major research challenges.Cell models can effectively be used to simulate the pathological changes of diseases under controllable conditions,thus facilitating the investigation of the etiology and factors influencing sarcopenia,and providing an important approach for in-depth studies of its mechanism;however,there is currently no standardized cell model in the field of sarcopenia research.Commonly used cell models currently include models involving protein metabolism interventions,oxidative stress,and inflammatory response interventions.This review considers the commonly used skeletal muscle cell types and modeling method of sarcopenia,to provide a solid foundation and important method ological reference for further simulation of the pathological process of sarcopenia in subsequent experimental studies.

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.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

Energy metabolism disorders are a critical factor contributing to cognitive dysfunction.Astrocytes,as key suppliers of energy substrates to neurons,help to sustain normal cognitive function via their extensive energy metabolism activities in the brain,coordinated by various energy supply mechanisms.Imbalances in astrocyte-neuron energy metabolism coupling lead to abnormal neuronal activity,thereby driving the pathogenesis and progression of Alzheimer's disease(AD).It is therefore essential to investigate the pathological mechanisms and therapeutic targets associated with AD from the perspective of energy metabolism to support the future development of AD treatments and interventions.Traditional Chinese medicine(TCM),characterized by multi-component and multi-target effects,has shown potential efficacy for regulating cerebral energy metabolism,suggesting that modulating brain energy metabolism may represent a significant pathway by which TCM might ameliorate AD.This review systematically elucidates the mechanistic role of the dysregulation of astrocyte-neuron bioenergetic coupling in the pathogenesis and progression of AD,and critically evaluates recent advancements in therapeutic interventions mediated by TCM.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

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.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.