Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.

Background The Belt and Road Initiative is promoting the growth of the cross-border population, and there is still a lack of study on modifiable factors associated with health-related preventive behaviors among resident aliens in China. Public health events may highlight the relevant factors. Objective To conduct a pilot study to preliminarily identify potential modifiable factors associated with preventive behaviors among resident aliens in China, and to explore possible mediating effects of positivity and self-efficacy on the relationship between satisfaction of health services and preventive behaviors, aiming to provide ideas for further research in this direction. Methods A cross-sectional survey was conducted among foreigners in a city of East China by using snowball sampling in July 2023. Based on the protection motivation theory, the Self-Efficacy Scale, Positivity Scale, Preventive Behaviors Scale, and Satisfaction of Health Services Scale were adopted in the survey. Cronbach's α coefficient was used to evaluate scale reliability. A structural equation model was constructed for validity test and path analysis. Maximum likelihood method was used for parameter estimation, and bias-corrected percentile Bootstrap method was used to verify mediating effect. Results A total of 187 resident aliens were approached and 180 of them returned valid questionnaires. The Cronbach's α coefficients of the Self-Efficacy Scale, Positivity Scale, and Preventive Behaviors Scale were 0.904, 0.784, and 0.821, respectively. The M (P₂₅, P₇₅) scores of self-efficacy, positivity, preventive behaviors, and satisfaction of health services were 32 (27, 35), 29 (25, 30), 17 (14, 20), and 4 (3, 5), respectively. Statistically significant differences in the scores of preventive behaviors were identified among the participants by religious belief, geographical location, and economy (P<0.05). The results of path analysis showed that satisfaction of health services, positivity, and self-efficacy had direct positive effects on preventive behaviors (P<0.05), and positivity and self-efficacy played multiple mediation roles in the relationship between satisfaction of health services and preventive behaviors. The results of mediating effect test showed that the indirect effects of the three identified paths mediated by positivity and self-efficacy were statistically significant, and the total size of indirect effect was 0.316 (95%CI: 0.180, 0.466) that accounted for 61.2% of the total effect size. The strongest mediating path was satisfaction of health services→positivity→preventive behaviors, with an indirect effect size of 0.167 (95%CI: 0.046, 0.335) that accounted for 32.4% of the total effect size. Conclusion Future studies and policy formulation on preventive behaviors of foreigners in China should focus on the social demographic factors such as geographical location of home country, religious belief, and cultural customs. At the same time, the study of path relationship of preventive behaviors should embrace environmental factors, emotional factors, and cognitive factors.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

Objective : To explore the effects of an ultradian light cycle on the periodic expression of glutamate re⁃ ceptors in the suprachiasmatic nucleus and the lateral habenula nucleus. Methods : An ultradian light cycle T7 (3. 5 hours/3. 5 hours light : dark) was used to establish an ultradian light cycle model group and T24( 12 hours/ 12 hours light : dark) was used to establish control group. The expression of key proteins in the brain regions of the suprachiasmatic nucleus ( SCN) and the lateral habenula ( LHB) of the hypothalamus were analyzed by Western blot. Including glutaminergic receptors , pituitary adenylate cyclase activating polypeptide (PACAP) receptors , and downstream signaling molecules. Results : Western blot results showed that the expression of α⁃amino⁃3 ⁃hydroxy⁃5 ⁃methyl⁃4 ⁃isoxazole⁃propionic acid receptor subunit 2 (GluR2) in SCN under Zeitgeber time (ZT ) 1 and ZT 5 increased under an ultradian light cycle compared with normal photoperiod ( P < 0. 05 , P < 0. 01) , the overall expression of GluR2 in T7 group was higher than that in T24 group (P < 0. 01) , the overall expression of GluR2 in LHB group T7 was lower than that in T24 group (P < 0. 01) . Compared with T24 photoperiod , the overall expression of N ⁃methyl⁃D ⁃aspartic acid receptor subunit 2 (NR2B) in SCN increased under T7 photoperiod (P < 0. 05) , the overall expression of phosphorylation of extracellular signal⁃related kinase ( P⁃ERK) in LHB significantly increased under T7 photoperiod (P < 0. 05) . Conclusion An ultradian light cycle would cause an up⁃regulating of GluR2 and NR2B expression , a down⁃regulating of GluR2 expression and up⁃regulating P ⁃ERK expression in LHB.

Background Immigrant health is an key node in achieving the goal of universal health coverage proposed by 2030 Agenda for Sustainable Development. The shock of severe public health emergency may exacerbate the original health-related contradictions of this group and bring more negative health effects. Objective To identify academic research hotspots and directions of immigrant health, and to examine trends in research hotspots before and after the public health emergency, so as to provide references to study immigrant health and response to public health emergency in the future. Methods Articles (document type) included in Web of Science core collection from 2017-01-01 to 2022-12-31 were retrieved. Microsoft Excel 2019 was used for descriptive analysis of included papers. VOSviewer 1.6.19 and CiteSpace 6.1.R6 were combined to draw cooperation maps of authors, institutions, and countries/areas to understand their cooperation and communication, and to draw keywords co-occurrence map, keywords clusters map, and keywords burst map to examine the hotspots and trends of immigrant health research before and after public health emergency. Results A total of 5997 papers pertaining to immigrant health from 2017 to 2022 were included, and the number of publications every year were overall on the rise generating a group of productive core authors. Institutions from the United States, Canada, and Northern Europe not only tightly cooperated within their countries/areas, but also cooperated frequently among countries/areas, forming an international cooperation network with the United States as its core. The keywords co-occurrence map showed that from 2017 to 2022, the research hotspots of immigrant health mainly focused on target groups of women, children, and refugees, and the study topics of mental health, acculturation, and care. The results of cluster analysis and further extraction found that the research topics in this field were divided into five categories: maternal and child health care, acculturation and mental health, health services, health equity, and chronic disease. The keywords burst map revealed that the research hotspots shifted from ethnic group, risk behavior, and sexes to COVID-19, health equity, social isolation, and victimization under the impact of public health emergency. Conclusion The cooperation and communication among study teams, institutions, and countries/areas have promoted the development of immigrant health study. Public health emergency has exacerbated the existing vulnerability of immigrants, and the topics related to health equity and social isolation of immigrants have raised attention becoming the research forefront. It is suggested that under the impact of public health emergency, corresponding public health policies are needed to mitigate health inequities and social support is also required for immigrants to ensure their physical and mental health.

China has entered the task stage of comprehensive medical insurance payment reform, but there are problems restricting the development of innovative medical technology in the reform of diagnosis-related groups(DRG) payment system. The author introduced the international definition and scope of innovative medical technology, and summarized the preconditions and payment policy of short-term payment of innovative medical technology under the DRG payment system; And put forward suggestions in line with China′s actual situation, including clarifying the definition of innovative medical technology, setting access conditions for additional payment or actual payment, setting up special transition funds for high-value innovative drugs, clarifying the payment amount of innovative medical technology, and formulating payment strategies for innovative medical technology.

Background As traditional chemical and physical hazards as well as associated adverse health outcomes in workplace were wildly controlled in the past half century, the prevalence and disease burden of low back pain (LBP) have drawn more and more attention and become one of the important public health problems in the world. Objective To analyze the health loss and attributable disease burden of ergonomic risk factors for LBP in two major categories of occupations in China, aiming to provide evidence for formulating effective prevention and control policies of LBP in the workplace. Methods Based on the methodological framework of the Global Burden of Disease Study (GBD), a meta-analysis was firstly applied to summarize relevant literature results and estimate the prevalence of LBP in two occupational groups (including technicians and associate professionals and machine operators and assemblers) by different age groups in China. Then important epidemiologic parameters (including disability weight, remission rate, and incidence) from GBD 2019 were used to estimate mean duration of disease and age at onset using DisMod II software, and to calculate health loss indexes in the selected occupational groups in China in 2013, such as years lived with disability (YLD) and disability-adjusted life year (DALY) of LBP and its attributable fractions by ergonomic risk factors, which were compared to the outcome of GBD 2013. Results After the adjustment by DisMod II, the prevalence rate of LBP was 13.00% in technicians and associate professionals (11.25% for males and 14.84% for females) and 14.80% in machine operators and assemblers (13.56% for males and 16.10% for females) in 2013, which increased with age. The DALY rate of LBP was 8.02‰ in technicians and associate professionals (7.68‰ for males and 8.33‰ for females) and 10.34‰ in machine operators and assemblers (10.30‰ for males and 10.44‰ for females), which also showed an overall increasing trend with age. In 2013, the population attributable fraction (PAF) of ergonomic risk factors to LBP was 11.42% in technicians and associate professionals and 29.17% in machine operators and assemblers. The DALY of LBP attributable to ergonomics risk factors was 4498 person-years (2108 person-years for males), with the highest DALY in the 45-49 year group (951 person-years), and the attributable DALY rate was 0.92‰ in technicians and associate professionals. The DALY of LBP attributable to ergonomics risk factors was 48529 person-years (33046 person-years for males), with the highest DALY in the 40-44 year group (10852 person-years), and the attributable DALY rate was 3.02‰ in machine operators and assemblers. Regarding LBP-associated DALY rate, in the 20 years of age and above group, both occupational groups (technicians and associate professionals: 8.06‰, machine operators and assemblers: 10.66‰) showed higher values than the general population (3.55‰). In the 20 years of age and above group, the DALY rates attributable to ergonomic risk factors with the order from high to low were machine operators and assemblers (3.11‰), general population (1.10‰) and technicians and associate professionals (0.92‰). Conclusion The LBP-associated disease burden is heavier in the two Chinese occupational groups than in general population. Reducing the disease burden of LBP by interventions targeting ergonomic risk factors in machine operators and assemblers is more effective than that in technicians and associate professionals as the results of attributable burden of disease suggest.

Objective:To evaluate the effect of clinical pathway implementation on medical efficiency and medical expenses of patients with two common rheumatic immune diseases " rheumatoid arthritis" and " ankylosing spondylitis" diseases by using diagnosis related group (DRG) related indicators.Methods:The data of patients with two common rheumatic immune diseases " rheumatoid arthritis" and " ankylosing spondylitis" included in the clinical pathway management from January 2017 to December 2019 in the Department of Rheumatology and Immunology of Jinhua Hospital, Zhejiang University School of Medicine were carried out. The impact of clinical pathway implementation on the average hospital stay, average cost and average drug cost of patients with the two diseases were analyzed and compared , so as to evaluate the effect of the implementation of the clinical pathway.Results:From the implementation of clinical pathway in 2017 to 2019, the number of patients admitted and total medical specialty services in the two groups of " rheumatoid arthritis" and " ankylosing spondylitis" increased year by year ( P<0.01). The average length of stay, average cost and average drug cost of patients in the " rheumatoid arthritis" disease group decreased year by year, with statistically significant differences between groups (all P<0.01). The average length of stay in the ankylosing spondylitis group was shortened year by year, and the difference was statistically significant ( P<0.01). Compared with 2017, the average cost in 2018 decreased significantly, and the difference was statistically significant ( P<0.01). There was no significant difference in average cost between 2018 and 2019 ( P>0.05). The average cost in 2018 was significantly higher than that in 2017 ( P<0.05). After analyzing the causes and optimizing the clinical pathway, the average cost in 2019 was significantly lower than that in 2018 ( P<0.01). Conclusions:Through the implementation of clinical pathways and continuous optimization of pathway connotation during use, the diagnosis and treatment efficiency of patients with " rheumatoid arthritis" and " ankylosing spondylitis" can be significantly improved, and medical costs can be reduced, which is in line with the current medical reform needs.

Rheumatoid arthritis (RA) is a chronic erosive arthritis. Early diagnosis, standardized treatment and regular monitoring of the disease will effectively mitigate disease progression and reduce the disability rate. Currently, traditional synthetic disease-modifying antirheumatic drugs (DMARDs) are used alone or in combination with new biological DMARDs or targeted synthetic DMARDS in the treatment of RA, resulting in effective remission in some refractory patients. However, the efficacy and toxicities of different treatments varies. With the development of proteomic and epigenetic technologies, some proteins, non-coding RNAs, and anti-drug antibodies (ADA) have been identified as potential markers for early diagnosis, concomitant diagnosis and disease assessment of RA. We summarized and analyzed the application prospects of novel RA diagnosis markers, including serum proteins, cell membrane proteins, non-coding RNAs, and ADA, with the aim of promoting the application of new markers that allow more precise diagnosis and treatment of RA.