BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

OBJECTIVE To screen endogenous differential metabolites in mice that die from chlor-promazine(CPZ)poisoning and investigate the detoxification mechanism of triheptanoin(TriHep)against CPZ-induced lethality.METHODS Mice were randomly divided into the following groups(half male and half female):normal control,CPZ 2.5LD50,CPZ LD50 intoxication(CPZI),CPZ LD50 death(CPZD),TriHep-control,and TriHep-intervention(TriHep+CPZ LD50).The CPZ 2.5LD50,CPZI and CPZD groups were intragastrically given a corresponding dose of CPZ,respectively.The TriHep-control group and the TriHep-intervention group were intragastrically given saline and CPZ LD50 respectively before being intragastrically given TriHep(3 μL·g-1)10 min later.Plasma samples from the CPZ 2.5LD50 group and normal control group were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)for metabolite identification and quantification.MetaboAnalyst 5.0 was employed to perform principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and metabolic pathway analysis to screen and identify differential metabolites.More comparisons were made of the levels of differential metabolites in plasma between the normal control,CPZI,CPZD,TriHep-intervention,and TriHep-control groups.RESULTS In the PCA score plot,metabolomic samples from the CPZ 2.5LD50 group and normal control group showed clear separation,indicating distinct clus-tering patterns.Primary screening under three conditions,including P＜0.05,variable importance in projec-tion(VIP)score≥ 1 and fold change(FC)≥1.5 or ≤0.67 for a comparison of CPZ 2.5LD50 group with normal control group 28 metabolites were identified.Following quantitative enrichment and structural identifica-tion,three significantly differential metabolites were confirmed:acetylcarnitine,propionylcarnitine,and succinic acid.Compared with the normal control group,both CPZI and CPZD groups showed signifi-cantly decreased plasma levels of acetylcarnitine and propionylcarnitine,while the succinic acid content was markedly increased in the CPZD group.In the TriHep control group,levels of acetylcarnitine and succinic acid were significantly elevated,with no significant change in propionylcarnitine levels.Com-pared with the CPZI group,the CPZD group showed a significant increase in plasma succinic acid levels,but no significant change was observed in the acetylcarnitine content.The TriHep-intervention group demonstrated metabolite profiles(all the three differential metabolites)similar to those in the CPZI group,with significantly reduced propionylcarnitine and succinic acid concentrations compared to the CPZD group.CONCLUSION In the early stage of CPZ intoxication,TriHep can alleviate CPZ poisoning via acetylcarnitine,which can stabilize the level of succinic acid in plasma via indirect succinic acid replenishment.

OBJECTIVE To screen endogenous differential metabolites in mice that die from chlor-promazine(CPZ)poisoning and investigate the detoxification mechanism of triheptanoin(TriHep)against CPZ-induced lethality.METHODS Mice were randomly divided into the following groups(half male and half female):normal control,CPZ 2.5LD50,CPZ LD50 intoxication(CPZI),CPZ LD50 death(CPZD),TriHep-control,and TriHep-intervention(TriHep+CPZ LD50).The CPZ 2.5LD50,CPZI and CPZD groups were intragastrically given a corresponding dose of CPZ,respectively.The TriHep-control group and the TriHep-intervention group were intragastrically given saline and CPZ LD50 respectively before being intragastrically given TriHep(3 μL·g-1)10 min later.Plasma samples from the CPZ 2.5LD50 group and normal control group were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)for metabolite identification and quantification.MetaboAnalyst 5.0 was employed to perform principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and metabolic pathway analysis to screen and identify differential metabolites.More comparisons were made of the levels of differential metabolites in plasma between the normal control,CPZI,CPZD,TriHep-intervention,and TriHep-control groups.RESULTS In the PCA score plot,metabolomic samples from the CPZ 2.5LD50 group and normal control group showed clear separation,indicating distinct clus-tering patterns.Primary screening under three conditions,including P＜0.05,variable importance in projec-tion(VIP)score≥ 1 and fold change(FC)≥1.5 or ≤0.67 for a comparison of CPZ 2.5LD50 group with normal control group 28 metabolites were identified.Following quantitative enrichment and structural identifica-tion,three significantly differential metabolites were confirmed:acetylcarnitine,propionylcarnitine,and succinic acid.Compared with the normal control group,both CPZI and CPZD groups showed signifi-cantly decreased plasma levels of acetylcarnitine and propionylcarnitine,while the succinic acid content was markedly increased in the CPZD group.In the TriHep control group,levels of acetylcarnitine and succinic acid were significantly elevated,with no significant change in propionylcarnitine levels.Com-pared with the CPZI group,the CPZD group showed a significant increase in plasma succinic acid levels,but no significant change was observed in the acetylcarnitine content.The TriHep-intervention group demonstrated metabolite profiles(all the three differential metabolites)similar to those in the CPZI group,with significantly reduced propionylcarnitine and succinic acid concentrations compared to the CPZD group.CONCLUSION In the early stage of CPZ intoxication,TriHep can alleviate CPZ poisoning via acetylcarnitine,which can stabilize the level of succinic acid in plasma via indirect succinic acid replenishment.

Objective To conduct the clinical and pathological evaluation on the conservative surgery in tubal pregnancy . Methods 513 cases of tubal pregnancy in this hospital from January 2006 to December 2012 were divide into the conservative sur-gery group(A ,314 cases) ,samlpintectomy group(B ,43 cases) and the medication conservative treatment group (C ,156 cases) .The hospitalization days ,HCG negative-conversion time ,cure rate ,re-pregnancy outcome ,pregnancy during 1-year follow-up were com-pared between the group A and C .In group B ,43 cases of tubal pregnancy and accomplishing fertility were firstly performed the tubal linear incision in the pregnant site ,then the biopsy was conducted after stopping bleeding and finally the salpingectomy in af-fected side was performed .The tubal electric injury degree by the unipolar or bipolar electrocoagulation and the pathological changes under light microscope were observed .Results The hospitalization days ,symptom relief rate ,HCG negative-conversion time ,cure rate and re-pregnancy outcome had statistical differences between the group A and C (P<0 .05) .Conclusion The tubal conserva-tive surgery has short hospitalization time ,high symptom relief rate ,high cure rate and few complications .The pathological observa-tion shows the localized electrocoagulation injury .The pregnancy rate after surgery is high .