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 understand the current status of the job competency of full-time healthcare-associated in-fection(HAI)management professionals in all levels and types of medical institutions across China,and provide in-formation and basis for professional training,competency improvement,and career planning.Methods The strati-fied sampling method was adopted to select HAI management professionals from medical institutions in 31 provin-cial-level administrative regions across the country as the research subjects.The designed content of questionnaire involved four parts,including the surveyed personnel's basic information,daily job competency assessment,satis-faction level towards the job,as well as opinions and suggestions on the management of full-time HAI management professionals.The assessment on daily job competency was divided into 13 dimensions,ranging from very incompe-tent to very competent in 5 levels.The scores of HAI management professionals with different professional back-grounds were compared and analyzed.Results A total of 8 709 valid questionnaires were collected,with 3 475 and 3 697 surveyed personnel from tertiary and secondary medical institutions,respectively,and 1 537 from primary or unclassified medical institutions.The overall average score for the competency assessment of full-time HAI manage-ment professionals was(4.17±0.80)points.The scores of professionals with different professional backgrounds,from high to low,were as follows:nursing([4.12±0.81]points),clinical medicine([4.07±0.86]points),pre-ventive medicine([3.93±0.92]points),laboratory medicine([3.88±0.93]points),pharmacy([3.86±0.94]points),and health management([3.85±0.95]points).For the core competency of HAI management professio-nals,such as monitoring and analyzing HAI cases,identifying and investigating HAI outbreaks,the assessment scores for professionals with medical backgrounds were the highest(both P＜0.05).For the basic work of HAI prevention and control,such as checking and guiding the implementation of rules and regulations,guiding occupa-tional protection,management and communication,and implementing HAI management training,professionals with a nursing background had the highest assessment scores(all P＜0.05).Full-time HAI management professionals were relatively satisfied with their training,while those with a background in preventive medicine had lower satisfac-tion with their training,career development,and job benefits(all P＜0.05).Conclusion There are significant differences in the competency of HAI management professionals with different professional backgrounds.It is nece-ssary to optimize division of labor and leverage the strengths,providing ideas and models for promoting the construction of a specialized and professional HAI management team.

Objective:To analyze the clinical features of postnatal cytomegalovirus (pCMV) infection in very preterm infants or very low birth weight infants.Methods:This was a case-control study. A total of 50 very preterm or very low birth weight infants who were hospitalized and diagnosed with pCMV infection in the Neonatal Intensive Care Unit of Children′s Hospital, Zhejiang University School of Medicine from January 2019 to June 2024, were enrolled as the pCMV group. Meanwhile, through propensity score matching, each infant in the pCMV group was paired with a very preterm or very low birth weight infant without cytomegalovirus infection during the same period, constituting the control group, also consisting of 50 cases. Subsequently, the pCMV group was divided into a treated subgroup and an untreated subgroup according to antiviral treatment. Clinical data of all enrolled infants, including clinical features, laboratory test results, and clinical outcomes were collected. Differences in relevant parameters were analyzed using with χ2 test or continuity-corrected χ2 test or Fisher′s exact test, independent-samples t test, Mann-Whitney U test as appropriate. Logistic regression was employed to analyze the risk factors, and Spearman correlation analysis was applied for non-normal distribution data or ordinal data. Results:There were no significant differences between the pCMV group and the control group in terms of gestational age, birth weight, proportion of male infants, Apgar score at the 1 st minute and 5 th minute and days of breastfeeding during the first 3 weeks of life (all P>0.05). Compared with the control group, the duration of hospital stay and invasive mechanical ventilation were both longer in the pCMV group (both P<0.05). The risks of bronchopulmonary dysplasia, retinopathy of prematurity, and hearing impairment were all higher in the pCMV group when compared with the control group(all P<0.05). The body weight and body length of the infants in the pCMV group were both lower than those of in the control group at the corrected gestational age of 36 weeks (both P<0.05). pCMV infections were associated with the increased incidence of both necrotizing enterocolitis ( OR=11.50, 95% CI 1.94-68.30, P=0.007) and severe intraventricular hemorrhage ( OR=6.82, 95% CI 1.19-38.97, P=0.031) in very preterm infants or very low birth weight infants. In the treated group, the platelet count was significantly improved after 6-8 weeks of antiviral treatment compared with that before treatment ((245±19)×10 9/L vs. (119±14)×10 9/L, t=5.37, P<0.001). Conclusions:Very preterm infants or very low birth weight infants with postnatal cytomegalovirus infection have longer hospital stay and duration of invasive mechanical ventilation, and are highly susceptible to bronchopulmonary dysplasia, retinopathy of prematurity, hearing impairment, and growth restriction. Antiviral treatment can effectively ameliorate thrombocytopenia in these infants.

Objective To analyze the risk factors associated with early recurrence after surgery for concomitant exo-tropia and establish a Nomogram prediction model.Methods A retrospective analysis was conducted on 243 cases(486 eyes)of concomitant exotropia treated in the Ophthalmology Department of our hospital from October 2015 to October 2021.The patients were divided into a training set(n=170)and a validation set(n=73)at a ratio of 7∶3.The Lasso re-gression,Boruta algorithm,and random forest algorithm were used to screen risk variables related to postoperative recur-rence of concomitant exotropia.The Spearman correlation analysis and variance inflation factor(VIF)were used to assess collinearity among variables,and a Nomogram prediction model was established using multivariate Cox regression.The re-ceiver operating characteristic curve,calibration curve,and clinical decision curve of the model at 6 months,18 months,and 24 months after surgery were used to assess the efficacy of the model.Results Three machine learning methods in-cluding Lasso regression,Boruta algorithm,and random forest algorithm identified six significant variables that might con-tribute to early recurrence after strabismus surgery from 22 risk variables in both training and validation sets.No collineari-ty was found among the six variables(r＜0.6,VIF＜5).Multivariate Cox regression revealed that strabismus type(inter-mittent exotropia),preoperative strabismus angle,best-corrected visual acuity(BCVA)in the right eye,BCVA in both eyes,and surgical procedures(unilateral lateral rectus recession)were risk factors for early recurrence after surgery for concomitant exotropia.Meanwhile,a Nomogram prediction model was constructed based on these 6 factors.The receiver operating characteristic,calibration,and clinical decision curves indicated that the prediction model had good accuracy,consistency,and clinical applicability.Conclusion Nomogram prediction model can effectively predict the risk of early recurrence after surgery for concomitant exotropia,and provides a reference for ophthalmologists to intervene early in pa-tients.

Objective To analyze the changing trend of the disease burden of age-related macular degeneration(AMD)in China from 1990 to 2021 and the impact of age,period,and cohort effects,and to predict the standardized prev-alence and disability-adjusted life year(DALY)rate of AMD in China from 2022 to 2035.Methods The data on the preva-lence of AMD,the number of AMD patients,DALYs,and DALY rates in China from 1990 to 2021 were obtained from the Global Burden of Disease(GBD 2021).The segmented regression model was used to analyze the trend changes in the prev-alence and DALY of patients with AMD in China,the age-period-cohort(APC)model was employed to estimate the age,period,and cohort effects related to the prevalence risk and DALY risk of AMD,and the Bayesian age-period cohort model was used to analyze the standardized prevalence and DALY rate of AMD in China from 2022 to 2035.Results Compared with 1990,the number of AMD patients and the prevalence of this disease in China in 2021 increased by 199.94％and 148.02％,respectively,and the DALYs and DALY rate increased by 183.95％and 134.80％,respectively,with the higher value of relevant indicators observed in females compared with males.From 1990 to 2021,the standardized prevalence of AMD in China showed an increasing trend,with the average annual percentage change(AAPC)being 0.17％.In contrast,the standardized DALY rate of AMD showed a decreasing trend,with the AAPC being-0.03％.The results of the age-peri-od-cohort model showed that the longitudinal age curves for both the prevalence and DALY rate of AMD in China showed an increasing and then decreasing trend,peaking at 85-89 years of age.Over time,the prevalence risk of AMD increased and then decreased,while the DALY risk continued to decline.The birth cohort analysis results showed that the overall fluctua-tion of the AMD prevalence risk cohort effect in China was small,with a decline first and then a fluctuating increase.Mean-while,the DALY risk gradually decreased as the birth cohort moved backward.It can be predicted that both the standard-ized prevalence and the standardized DALY rate of AMD may present an upward trend in China from 2022 to 2035.Conclu-sion From 1990 to 2021,the standardized prevalence of AMD in China displays an upward trend,while its standardized DALY rate exhibits a downward trend.Notably,the disease burden is more pronounced in the female population compared with the male population.With the continued aging of the population,it can be predicted that both the standardized preva-lence and DALY rate of AMD will escalate from 2022 to 2035.This finding underscores the need for targeted interventions,particularly for elderly women.Meanwhile,it is necessary to enhance health education for the whole population and formu-late effective public health policies to alleviate the disease burden associated with AMD in China.

Objective To understand the current status of the job competency of full-time healthcare-associated in-fection(HAI)management professionals in all levels and types of medical institutions across China,and provide in-formation and basis for professional training,competency improvement,and career planning.Methods The strati-fied sampling method was adopted to select HAI management professionals from medical institutions in 31 provin-cial-level administrative regions across the country as the research subjects.The designed content of questionnaire involved four parts,including the surveyed personnel's basic information,daily job competency assessment,satis-faction level towards the job,as well as opinions and suggestions on the management of full-time HAI management professionals.The assessment on daily job competency was divided into 13 dimensions,ranging from very incompe-tent to very competent in 5 levels.The scores of HAI management professionals with different professional back-grounds were compared and analyzed.Results A total of 8 709 valid questionnaires were collected,with 3 475 and 3 697 surveyed personnel from tertiary and secondary medical institutions,respectively,and 1 537 from primary or unclassified medical institutions.The overall average score for the competency assessment of full-time HAI manage-ment professionals was(4.17±0.80)points.The scores of professionals with different professional backgrounds,from high to low,were as follows:nursing([4.12±0.81]points),clinical medicine([4.07±0.86]points),pre-ventive medicine([3.93±0.92]points),laboratory medicine([3.88±0.93]points),pharmacy([3.86±0.94]points),and health management([3.85±0.95]points).For the core competency of HAI management professio-nals,such as monitoring and analyzing HAI cases,identifying and investigating HAI outbreaks,the assessment scores for professionals with medical backgrounds were the highest(both P＜0.05).For the basic work of HAI prevention and control,such as checking and guiding the implementation of rules and regulations,guiding occupa-tional protection,management and communication,and implementing HAI management training,professionals with a nursing background had the highest assessment scores(all P＜0.05).Full-time HAI management professionals were relatively satisfied with their training,while those with a background in preventive medicine had lower satisfac-tion with their training,career development,and job benefits(all P＜0.05).Conclusion There are significant differences in the competency of HAI management professionals with different professional backgrounds.It is nece-ssary to optimize division of labor and leverage the strengths,providing ideas and models for promoting the construction of a specialized and professional HAI management team.

Objective To analyze the risk factors associated with early recurrence after surgery for concomitant exo-tropia and establish a Nomogram prediction model.Methods A retrospective analysis was conducted on 243 cases(486 eyes)of concomitant exotropia treated in the Ophthalmology Department of our hospital from October 2015 to October 2021.The patients were divided into a training set(n=170)and a validation set(n=73)at a ratio of 7∶3.The Lasso re-gression,Boruta algorithm,and random forest algorithm were used to screen risk variables related to postoperative recur-rence of concomitant exotropia.The Spearman correlation analysis and variance inflation factor(VIF)were used to assess collinearity among variables,and a Nomogram prediction model was established using multivariate Cox regression.The re-ceiver operating characteristic curve,calibration curve,and clinical decision curve of the model at 6 months,18 months,and 24 months after surgery were used to assess the efficacy of the model.Results Three machine learning methods in-cluding Lasso regression,Boruta algorithm,and random forest algorithm identified six significant variables that might con-tribute to early recurrence after strabismus surgery from 22 risk variables in both training and validation sets.No collineari-ty was found among the six variables(r＜0.6,VIF＜5).Multivariate Cox regression revealed that strabismus type(inter-mittent exotropia),preoperative strabismus angle,best-corrected visual acuity(BCVA)in the right eye,BCVA in both eyes,and surgical procedures(unilateral lateral rectus recession)were risk factors for early recurrence after surgery for concomitant exotropia.Meanwhile,a Nomogram prediction model was constructed based on these 6 factors.The receiver operating characteristic,calibration,and clinical decision curves indicated that the prediction model had good accuracy,consistency,and clinical applicability.Conclusion Nomogram prediction model can effectively predict the risk of early recurrence after surgery for concomitant exotropia,and provides a reference for ophthalmologists to intervene early in pa-tients.

Objective To analyze the changing trend of the disease burden of age-related macular degeneration(AMD)in China from 1990 to 2021 and the impact of age,period,and cohort effects,and to predict the standardized prev-alence and disability-adjusted life year(DALY)rate of AMD in China from 2022 to 2035.Methods The data on the preva-lence of AMD,the number of AMD patients,DALYs,and DALY rates in China from 1990 to 2021 were obtained from the Global Burden of Disease(GBD 2021).The segmented regression model was used to analyze the trend changes in the prev-alence and DALY of patients with AMD in China,the age-period-cohort(APC)model was employed to estimate the age,period,and cohort effects related to the prevalence risk and DALY risk of AMD,and the Bayesian age-period cohort model was used to analyze the standardized prevalence and DALY rate of AMD in China from 2022 to 2035.Results Compared with 1990,the number of AMD patients and the prevalence of this disease in China in 2021 increased by 199.94％and 148.02％,respectively,and the DALYs and DALY rate increased by 183.95％and 134.80％,respectively,with the higher value of relevant indicators observed in females compared with males.From 1990 to 2021,the standardized prevalence of AMD in China showed an increasing trend,with the average annual percentage change(AAPC)being 0.17％.In contrast,the standardized DALY rate of AMD showed a decreasing trend,with the AAPC being-0.03％.The results of the age-peri-od-cohort model showed that the longitudinal age curves for both the prevalence and DALY rate of AMD in China showed an increasing and then decreasing trend,peaking at 85-89 years of age.Over time,the prevalence risk of AMD increased and then decreased,while the DALY risk continued to decline.The birth cohort analysis results showed that the overall fluctua-tion of the AMD prevalence risk cohort effect in China was small,with a decline first and then a fluctuating increase.Mean-while,the DALY risk gradually decreased as the birth cohort moved backward.It can be predicted that both the standard-ized prevalence and the standardized DALY rate of AMD may present an upward trend in China from 2022 to 2035.Conclu-sion From 1990 to 2021,the standardized prevalence of AMD in China displays an upward trend,while its standardized DALY rate exhibits a downward trend.Notably,the disease burden is more pronounced in the female population compared with the male population.With the continued aging of the population,it can be predicted that both the standardized preva-lence and DALY rate of AMD will escalate from 2022 to 2035.This finding underscores the need for targeted interventions,particularly for elderly women.Meanwhile,it is necessary to enhance health education for the whole population and formu-late effective public health policies to alleviate the disease burden associated with AMD in China.

Objective:To analyze the clinical features of postnatal cytomegalovirus (pCMV) infection in very preterm infants or very low birth weight infants.Methods:This was a case-control study. A total of 50 very preterm or very low birth weight infants who were hospitalized and diagnosed with pCMV infection in the Neonatal Intensive Care Unit of Children′s Hospital, Zhejiang University School of Medicine from January 2019 to June 2024, were enrolled as the pCMV group. Meanwhile, through propensity score matching, each infant in the pCMV group was paired with a very preterm or very low birth weight infant without cytomegalovirus infection during the same period, constituting the control group, also consisting of 50 cases. Subsequently, the pCMV group was divided into a treated subgroup and an untreated subgroup according to antiviral treatment. Clinical data of all enrolled infants, including clinical features, laboratory test results, and clinical outcomes were collected. Differences in relevant parameters were analyzed using with χ2 test or continuity-corrected χ2 test or Fisher′s exact test, independent-samples t test, Mann-Whitney U test as appropriate. Logistic regression was employed to analyze the risk factors, and Spearman correlation analysis was applied for non-normal distribution data or ordinal data. Results:There were no significant differences between the pCMV group and the control group in terms of gestational age, birth weight, proportion of male infants, Apgar score at the 1 st minute and 5 th minute and days of breastfeeding during the first 3 weeks of life (all P>0.05). Compared with the control group, the duration of hospital stay and invasive mechanical ventilation were both longer in the pCMV group (both P<0.05). The risks of bronchopulmonary dysplasia, retinopathy of prematurity, and hearing impairment were all higher in the pCMV group when compared with the control group(all P<0.05). The body weight and body length of the infants in the pCMV group were both lower than those of in the control group at the corrected gestational age of 36 weeks (both P<0.05). pCMV infections were associated with the increased incidence of both necrotizing enterocolitis ( OR=11.50, 95% CI 1.94-68.30, P=0.007) and severe intraventricular hemorrhage ( OR=6.82, 95% CI 1.19-38.97, P=0.031) in very preterm infants or very low birth weight infants. In the treated group, the platelet count was significantly improved after 6-8 weeks of antiviral treatment compared with that before treatment ((245±19)×10 9/L vs. (119±14)×10 9/L, t=5.37, P<0.001). Conclusions:Very preterm infants or very low birth weight infants with postnatal cytomegalovirus infection have longer hospital stay and duration of invasive mechanical ventilation, and are highly susceptible to bronchopulmonary dysplasia, retinopathy of prematurity, hearing impairment, and growth restriction. Antiviral treatment can effectively ameliorate thrombocytopenia in these infants.

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.