Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To understand the epidemiological characteristics and trends of injury in older adults in Jiangsu Province from 2006 to 2022 and provide a scientific basis for developing prevention and control measures.Methods:The data on injury cases aged 60 and older were collected from 12 sentinel hospitals in Jiangsu Province during 2006-2022. The study analyzed the proportion of injury cases among the elderly in the overall population and calculated the annual percent change and average annual percent change (AAPC). A pairwise comparison between groups was performed, and the differences were judged according to the adjusted standardized residuals.Results:From 2006 to 2022, there were 218 426 injury cases among individuals aged 60 and older in Jiangsu Province, which accounted for an increasing proportion of injury cases within the entire population (AAPC=3.17%, P<0.001). The first five causes of elderly injury were falls (42.06%), road traffic injuries (20.20%), animal injuries (11.45%), knife/sharp injuries (9.43%), and blunt injuries (8.13%). From 2006 to 2022, the proportion of falls, animal injuries, and knife/sharp injuries among the elderly aged ≥60 showed an increasing trend, while the proportion of road traffic injuries and blunt injuries decreased (all P<0.001). The incidence of injury was highest in October, with a daily incidence peak between 8:00 and 10:00. Leisure activities (40.34%) were the major activity leading to injury. The injury occurred mainly at home (53.74%), and the injury intention was mainly unintentional (97.41%), all of which showed an increasing trend ( P<0.001). The injuries were mainly bruises (36.00%), and the most common injured positions of the body were low limbs (27.55%), all of which showed a decreasing trend ( P<0.001). About 69.80% of cases were slight, and 79.38% were discharged after treatment, which showed an increasing trend ( P<0.001). Conclusions:The injury data for individuals aged 60 and older in Jiangsu Province exhibited varying trends from 2006 to 2022. There was a noticeable increase in the proportion of elderly injury cases within the overall injury population, as well as an upward trend in falls, animal injuries, and knife/sharp injuries as leading causes of injury. It is imperative to actively develop prevention measures based on the epidemiological characteristics and evolving trends of elderly injuries in Jiangsu Province.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Objective To investigate the expression,function and prognostic value of Ras-related C3 botulinum toxin substrate 2(RAC2)in breast cancer.Methods The expression profile of RAC2 mRNA was investigated in the TCGA-BRCA cohort,the prognostic value was analyzed using the Kaplan-Meier algorithm,the potential molecular function was investigated by gene set enrichment analysis,the relationship between RAC2 and immune infiltration was analyzed by Estimate and Cibersort algorithms,and the association between Rac2 and mutation spectrum was evaluated by maftools software package.The RNA-seq software package"pRRophetic"was used to predict the effect of chemotherapy drugs.In the validation cohort,Immunohistochemistry(IHC)staining was performed on tumor pathological sections of patients.Kaplan-Meier survival analysis and cox regression analysis were used to analyze the relationship between RAC2 and the prognosis of breast cancer.Results Bioinformatics analysis showed that the expression of RAC2 was up-regulated in estrogen receptor(ER)positive BC.In the Pam50 molecular subtype of BC,its expression decreased in the order of normal-like group,triple negative group,HER2 overexpression group,Luminal A group and Luminal B group.BC patients with high RAC2 expression had better overall survival(OS)and recurrence-free survival(RFS).The results of the validation cohort confirmed that RAC2 can be used as an independent predictor of BC prognosis.RAC2 was involved in the process of immune infiltration of tumor cells,and its high expression was mainly related to the mutations of CCDC168,VPS13C and AHNAK genes.Its up-regulation increased the drug sensitivity of doxorubicin,cisplatin,paclitaxel and gemcitabine.In terms of metabolism,it was negatively correlated with glycolysis and pentose phosphate pathway(PPP),and positively correlated with fatty acid oxidation(FAO)and glutamine metabolism.Conclusion High expression of RAC2 is associated with a good prognosis of BC and plays a role in the metabolism and immune infiltration.Further study on the molecular mechanism of RAC2 may provide new strategies for the prognosis and treatment of BC.

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

Objective: To investigate the intake of liquid dairy products and identify its influencing factors among the fourth grade students in Nanjing City. Methods: The fourth grade students were selected as the study subjects in Nanjing City using a multi-stage random cluster sampling method in September 2020. Their general information, frequency of liquid dairy product intake one week prior to survey and mean intake amount per time were collected. According to the 2016 Dietary Guidelines for Chinese Residents, weekly intake of liquid dairy products of 2 100 g and greater was defined eligible. Factors affecting the frequency and amount of liquid dairy product intake were identified using multivariable logistic regression analysis. Results: A total of 2 268 questionnaires were allocated and 2 216 valid questionnaires were recovered, with an effective recovery rate of 97.71%. The respondents included 1 199 boys ( 54.11% ) and 1 017 girls ( 45.89% ). The frequency of liquid dairy product intake was (6.41±4.86) times per week, and the median intake amount was 1 250.00 g per week (interquartile range, 1 750.00 g per week). There were 607 students ( 27.39% ) consuming liquid dairy products of 2 100 g and greater a week, and 1 016 students ( 45.85% ) consumed liquid dairy products for 7 times and more a week. Multivariable logistic regression analysis showed that living in urban areas ( OR=1.204, 95%CI: 1.005-1.443 ), knowing nutrition labels ( OR=1.221, 95%CI: 1.021-1.460 ), periodical measurement of body weight (OR=1.486, 95%CI: 1.098-2.011) and restricted intake of sugar-containing drinks ( OR=1.264, 95%CI: 1.005-1.590 ) facilitated the intake of liquid dairy products for 7 times and more a week, and students with periodical measurement of body weight were more likely to consume liquid dairy products for 2 100 g and greater a week ( OR=1.821, 95%CI: 1.240-2.676 ). Conclusions Inadequate intake of liquid dairy products is found among the fourth grade students in Nanjing City. Residence, awareness of nutrition labels, periodical measurement of body weight, and parental restriction of sugar-containing drink intake affect the intake of liquid dairy products.

Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in 2020. A large number of studies have proved that tumor infiltrating lymphocytes (TILs) are lethal to tumors and play an important role in identifying tumor antigens. Therefore, the application of TILs in clinical immunotherapy and prognosis assessment of breast cancer has attracted wide attention. In this review, the basic research progress and clinical application of TILs in different molecular types of breast cancer are reviewed, and the value of TILs in judging breast cancer prognosis and predicting the therapeutic effect of clinical immunotherapy is evaluated.

Objective:To explore the association between different paths of diabetic progression and dyslipidemia in a Nanjing adult population.Methods:From January 2017 to June 2018, 61, 098 local residents aged ≥18 years were selected from the Chronic Disease and Risk Factor Surveillance database in Nanjing using a five-stage stratified cluster random sampling method. Data were collected through interview surveys, physical measurements, and laboratory examinations. The relationship between different rates of diabetic progression and dyslipidemia was analyzed using complex weighting and multilevel models.Results:In all, 60, 283 participants were finally enrolled in the study. The weighted proportions of normal glucose regulation, pre-diabetes, and diabetes were 71.2%, 17.9%, and 10.9%, respectively. The overall weighted prevalence, awareness, treatment, and control of dyslipidemia were 29.8%, 41.6%, 28.9%, and 22.9%, respectively. The weighted proportion of patients with dyslipidemia combined with diabetes was 52.9%. The weighted prevalence of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 24.0%, 38.8%, and 52.9%, respectively (all P<0.001). Compared to the normal glucose regulation group, subjects with pre-diabetes ( OR = 2.04, 95% CI: 1.95-2.13) or diabetes ( OR= 3.87, 95% CI: 3.66-4.10) had possibly gradually increased risks of dyslipidemia (all P<0.001). In addition, there was an increasing trend toward awareness, treatment, and control of dyslipidemia with increasing levels of glucose (all P<0.001). The weighted awareness of dyslipidemia in adults with normal glucose regulation, pre-diabetes, and diabetes was 36.3%, 42.8%, and 56.2%, respectively; the corresponding rates of treatment and control were 23.7%, 29.2%, and 43.7%, and 20.4%, 22.6%, and 30.1%, respectively. Conclusion:Diabetes and dyslipidemia have become the main chronic diseases in the Nanjing population.

Objective: To explore the knowledge and consumption of sugar sweetened beverage(SSB) and its influencing factors among third grade primary students, to provide basis for take targeted intervention measures. Methods: In September 2019, 1 686 primary school students of grade 3 were randomly selected from 2 primary schools in 1 urban area and 1 outer suburb area of 12 districts in Nanjing by using a multistage cluster sampling method，and a self administered questionnaire were offered to them to collect the knowledge about sugar sweetened beverage and its intake. Results: Totally 753 students (44.7%) answered 6 or more SSB knowledge questions correctly, and the rate of 389 students (50.2%) in urban areas was higher than that of 364 students (40.0%) in suburban areas. There were 780 (46.3%) students who knew that dairy containing beverage could not replace milk, the rate of 403 (52.0%) students in urban area was higher than that of 377 (41.4%) students in suburban area (χ 2=17.76, 18.99, P<0.05). Logistic regression analysis showed that compared with the frequency of consumption of SSB <1 time per week, the behavioral risk factors of primary school students who drink SSB ≥4 times per week were:urban area (OR=1.55), low parents educational level (OR=2.44), and frequent storage of SSB at home (OR=1.62). The protective factors were as follows:duration of extracurricular physical activity <120 min/week (OR=0.68), video time <120 min/day (OR=0.50), awareness rate of SSB ≥60% (OR=0.75), and restriction of high sugar snacks by parents (OR=0.60). Conclusion The knowledge associated with SSB among third grade students in Nanjing is relatively low. Consumption of SSB has been influenced by areas, parents educational level, knowledge about SSB and family factors. SSB consumption among primary students should be interfered at the school and family level. The health food education need to carry out based on the school and family, so as to create a supportive atmosphere integrating the school family to drink less sugar beverages.