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.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

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.

Radar uses electromagnetic waves to detect， track and locate objects at certain distances， which is widely used in military， meteorological， navigation and other fields. Radar emits electromagnetic waves outward and produces non-ionizing radiation， which may be considered as a physical occupational hazard. Epidemiological surveys found that long-term exposure to radar is associated with various adverse health effects， which may be correlated to transmitted power and frequency of radar， location of radar antenna， position of workers， and shielding effectiveness of cabins where work station is located. Based on radar frequency and electromagnetic radiation intensity， this study summarizes the health effects of radar on occupational population exposed to radar.

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.