The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Traditional symptom management methods are difficult to efficiently and accurately intervene in symptom networks related to mental illness. Bridge symptoms are the most core symptom in the symptom network, and symptom management for bridge symptoms can effectively improve other related symptoms management of mental illness. This paper reviews the overview, identification indicators and methods, characteristics of bridge symptoms, and its application significance in symptom management of mental illness patients, aiming to provide reference for nurses to implement efficient and accurate symptom management for patients with mental illness.

Objective: To understand the characteristic of height growth among preschool children with normal physique, overweight and obese, and in order to provide basis for proper physical growth intervention of preschool children. Methods: Cluster sampling method was used and preschool children of kindergartens in 7 cities were selected, height and weight was measured, the information of birth date and sex were collected by parents’ questionnaires. The "WHO Child Growth Standards" was used for evaluate children’s height and body mass index. ANOVA analysis and Wilcoxon rank sum test were used for statistic analysis. Results: There were 2 479 children who were normal weight, overweight and obese at baseline and were followed up for 2 years. The detection rate of Conclusion Parents and practitioners in MCH should pay attention to the children’s height growth, especially on overweight and obese children. More in-depth research are needed to explore the relationship between children’s height and physique.

Objective:To collect the simple interventions in pediatric biomedical research and analyze the risk condition, to establish the minimal risk evaluation criteria, thus to provide the scientific method for the ethical re-view of pediatric biomedical research. Methods:The expert consultation was carried out on the minimal risk evalu-ation of the simple interventions for pediatric biomedical research, and 25 experts from 11 medical institutions car-rying out children' s clinical research were selected to conduct 2 rounds of expert consultation. Results:25 valid questionnaires were collected, and the positive coefficient of the respondents was 100％. The judgment and famili-arity or degree of attention on the related problems was 0 . 764 . The minimal risk evaluation criteria of 25 simple in-terventions in 4 dimensions were determined. Conclusion: We determine the minimal risk evaluation criteria for simple interventions in pediatric biomedical research using the Delphi method, and the research results were relia-ble and could provide a reference for the ethical review of pediatric biomedical research.

Objective To construct the growth percentile curves of weight-,length/height-,head circumference and BMI for 1 to 4 year-olds who had been breastfed in urban areas.Methods Data was from the longitudinal study on 1 025 breastfed children aged 1 to 4 years,in 8 urban areas during 2008-2012.MLwiN2.25 was selected to construct the multi-level models of weight-for-age,length for-age,head circumference-for-age and BMI-for-age.The models included many growth relevant factors including gender,age,family and social demographic characteristics,perinatal factors,parent biological characteristics,dietary patterns and diseases of childen.Based on these models,predicted values (P3,P15,P50,Ps5,P97) were estimated to fit the percentiles reference curves.Results The percentiles reference curves of weight-,length/height,head circumferenceand BMI-for-age for the 1-4 year-olds who had been breastfed in the urban areas were developed.Differences of all the indicators between boys and girls were statistically significant (P＜0.001).Weight,length/height,head circumference and BMI were higher in boys than those in girls,with an average differences as 0.56-0.76 kg,0.89-1.12 cm,0.64-0.91 cm and 0.31-0.52 kg/m2.Conclusion The percentiles reference curves on growth,constructed by the longitudinal observational data and scientific method,were important in reflecting the development ofbreastfed children in urban areas.

The social and behavioral research in promoting human health and the impact on human social relations and structures has been confirmed .With the development of social and behavioral science , the importance of ethics review for the research is also increased .Despite its uniqueness , the basic principles of ethics in social and behavioral research are consistent with other biomedical studies .This paper introduces ethics review points of social and behavioral research from the research design , risk and benefits , informed consent , deception and debriefing , expedited review , exemption of ethics review, privacy and confidentiality .This paper also introduces the relevant experiences from Europe and America giving references for the domestic professionals .

Based on a study of children’s behavior and psychological characteristics,the article introduced Maslow’s hierarchy of needs to discuss children’s special needs for medical environment.Hence the authors proposed to meet children’s physiological needs,security needs,social needs,esteem needs,and self-realization needs.Shanghai Children’s Hospital was cited as an example,to present the humanistic expression practices in designing children’s medical environment.