OBJECTIVE To explore the practice and application effect of lean Six Sigma （LSS） management in the cost- benefit management of PIVAS operation in a tertiary comprehensive hospital （hereinafter referred to as “S Hospital”）， providing reference for the operation and management of PIVAS in hospitals. METHODS The five steps （define， measure， analyze， improve and control， i.e. DMAIC） of LSS management were implemented for PIVAS operation cost-benefit of S Hospital， and lean management was implemented for its cost-benefit management elements （human resource cost， medical and health material cost， and all-in-one parenteral nutrition preparation income）. Several intervention measures including personnel training and performance assessment， refined management system of consumables， and doctor’s advice package of full parenteral nutrition were developed. Finally， the overall improvement effect was evaluated by the total benefit， total cost and net benefit of PIVAS. The effects of human resource allocation optimization and improvement were evaluated by the work efficiency， work quality， job satisfaction， turnover rate and accumulated rest days. The effects of consumables cost management were evaluated by the amount of medical and health materials cost. The improvement effects of all-in-one parenteral nutrition preparation income were evaluated by the profit amount， quantity and the proportion of single bottle of parenteral nutrition. RESULTS After implementing DMAIC in S Hospital， the total benefit of PIVAS was increased from （471 366.50±9 201.5） yuan/month to （479 679.50±14 320.14） yuan/month （P＞ 0.05）， the total cost was decreased from （305 878.88±3 201.75） yuan/month to （294 610.59±5 007.33） yuan/month （P＜0.05）， and the net benefit of PIVAS was increased by 11.83% compared with that before the improvement. The work efficiency， work quality and job satisfaction of employees were significantly improved， the accumulated rest days were significantly reduced， and the turnover rate of third-party employees was reduced from 15.0% before the improvement to 7.5% after the improvement. The cost of medical and health materials significantly decreased from （67 826.42±2 812.76） yuan/month before improvement to （56 384.33±4 607.67） yuan/month after improvement （P＜0.05）. The quantity of all-in-one parenteral nutrition was significantly increased from （1 263.75±135.83） group/month before improvement to （2 061.25±89.04） group/month after improvement （P＜0.05）， and the proportion of users of single bottle of parenteral nutrition in total users decreased from 93.25% before improvement to 58.75% after improvement. The profit of all-in-one parenteral nutrition was 63.18% higher than that before implementing DMAIC. CONCLUSIONS The implementation of PIVAS operation cost-benefit management based on DMAIC is conducive to strengthening the cost control of PIVAS and promoting the healthy development of PIVAS.

Objective: To investigate the expression of peroxiredoxin 4 (PRDX4) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration, and invasion of OSCC cells. Methods: The Cancer Genome Atlas(TCGA) database was used to analyze the expression of PRDX4 in OSCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot (WB) were used to detect the mRNA and protein expression of PRDX4 in OSCC cell lines and normal oral mucosal epithelial cells. PRDX4 was knocked down in CAL-27 cells and divided into two groups: the si-PRDX4 group and si-NC group. SCC-9 cells overexpressing PRDX4 were divided into two groups: the PRDX4 overexpression group (transfected with pcDNA3.1-PRDX4 plasmid) and the vector group (the control group; transfected with pcDNA3.1-NC plasmid). A cell counting kit-8 (CCK-8) and plate colony formation assay were used to detect cell proliferation. Transwell assay and cell scratch test were used to detect cell invasion and migration ability. WB was used to detect the effects of knockdown or overexpression of PRDX4, p38MAPK agonist or inhibitor on the expression of p38MAPK-related signaling pathway proteins, and epithelial mesenchymal transition proteins in OSCC cells. Results: PRDX4 was highly expressed in OSCC tissues and cell lines. The results of qRT-PCR and WB showed that PRDX4 was highly expressed in OSCC cell lines compared with normal oral mucosal epithelial cells. The CCK-8 assay showed that the si-PRDX4 group had significantly lower OD values than the si-NC group at 24, 48, and 72 h (P<0.05). The PRDX4 overexpression group had a significantly higher OD value than the vector group at 24, 48, and 72 h (P<0.05). The plate colony formation assay showed that the si-PRDX4 group had a significantly lower number of colonies than the si-NC group (P<0.05). The number of colonies formed in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The cell scratch test showed that the wound healing area of the si-PRDX4 group was less than that of the si-NC group (P<0.05). The scratch healing area of the PRDX4 overexpression group was significantly higher than that of the vector group (P<0.05). The Transwell invasion assay showed that the number of transmembrane cells in the si-PRDX4 group was lower than that in the si-NC group (P<0.05). The number of transmembrane cells in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The WB results showed that knockdown and overexpression of PRDX4 could downregulate and upregulate the expression of the p38MAPK signaling pathway and epithelial-mesenchymal transition related proteins, respectively, and the addition of p38MAPK agonist and inhibitor could significantly reverse the expression of related proteins. Conclusion PRDX4 is highly expressed in OSCC. Knocking down the expression of PRDX4 in OSCC cells can downregulate the expression of p38 MAPK signal axis and EMT-related signal proteins, thereby inhibiting the proliferation, migration, invasion, and epithelial-mesenchymal transition of cells.

The ethical review of clinical research on rare diseases is crucial in ensuring the scientific validity of the research and the rights and interests of the subjects. Starting from the definition of rare diseases， this paper analyzed the current situation of domestic and international regulations and ethical review in clinical research on rare diseases. It also explored the key elements of ethical review from the two dimensions of scientific and ethical aspects of clinical research， including research objectives， methods， risk and benefit assessment， researcher qualifications， research infrastructure， informed consent process， data security and privacy protection， and protection of vulnerable groups such as children. Regarding the ethical review of clinical research on rare diseases， strategies can be adopted such as strengthening the training of ethics review personnel， conducting multi-center collaborative reviews， and focusing on the long-term safety of trials， to improve the quality of ethical review， protect the safety of the subjects， and ensure the efficiency and quality of clinical research.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

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.

Cholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.

Cholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.

Cholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.

Cholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.