BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective To investigate the basic situation and occupational health conditions of nuclear medicine radiation workers in Jiangsu Province based on the research protocol developed by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences for the nationwide study on the health effects of nuclear medicine radiation in China, understand the impact of occupational radiation on the physical health of nuclear medicine radiation workers, and provide a basis for improving the occupational protection of nuclear medicine radiation workers and reducing the risk of occupational radiation-related health issues. Methods A census approach was used to collect general data and occupational health information of nuclear medicine radiation workers in Jiangsu Province. The analysis focused on the abnormalities in physical examination indicators among radiation workers of different genders, ages, and working years to evaluate the health effects of occupational radiation exposure. Results The occupational health examination data of 472 nuclear medicine radiation workers were collected from 76 medical institutions in Jiangsu Province. The results showed that the detection rate of abnormal hypothyroidism in female workers (8.90%) was higher than that in male workers (2.54%) (P=0.028). With increasing working years, the detection rates of cataract and continuous decrease in white blood cell count increased (P＜0.001). The multivariate logistic regression identified working years as a risk factor for cataract and continuous decrease in white blood cell count (OR=1.59, 95%CI=1.40-3.35, P=0.0003; OR=4.15, 95%CI=3.11-29.91, P=0.0001). In addition, working years was also a risk factor for hypertension, fatty liver, and tumor (OR=2.28, 95%CI=1.51-3.47, P=8.76 × 10⁻⁵; OR=1.69, 95%CI=1.10-2.58, P=0.0145; OR=2.04, 95%CI=1.00-4.16, P=0.0469). Conclusion The study found that working in nuclear medicine could increase the risk of various radiation-related diseases, and the risk is influenced by factors such as working years.

To investigate the effect of mitochondrial division inhibitor 1(Mdivi-1)on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its mechanism,female 8-week-old C57BU6 mice were recruited and randomly divided into control group,IMQ model group,IMQ+Mdivi-1 experiment group.IMQ was used to induce the psoriasis-like skin inflammation model in mice.The mice in the experiment group were injected intraperitoneally(i.p.)with Mdivi-1,and the mice in the control group and model group were injected with the same volume of solvent.The mice were sacrificed on the 7th day for sampling.Psoriasis area and severity index(PASI)score was used to evaluate the severity of skin lesions in each group;the reactive oxygen species(R0S)content in skin tissue was detected by fluorescence staining of frozen section;HE staining was used to observe the histomorphologic change of skin lesions;immunohistochemical staining was used to detect the expression of dynamin-related protein 1(Drp1)in the skin of mice;Western blot was used to detect the protein levels of Drp1,NLRP3 and IL-1β in the skin tissues of mice in each group;and the expressions of IL-17A and IL-18 in mouse serum were detected by ELISA.Data showed that the model group had typical psoriatic lesions such as erythema,scale and thickening,and the Mdivi-1 group demonstrated obvious reduction of the lesions.The PASI score of the experiment group was significantly lower than that of the model group.HE staining indicated that the epidermal thickness of the back skin in the treatment group was significantly lower than that in the model group,and Munro microabscess was significantly reduced.R0S fluorescence staining indicated that ROS content in the experiment group was significantly lower than that in the model group;immunohistochemical results showed that the expression of Drp1 protein in the experiment group was significantly lower than that in the model group;Western blot results showed that the expression levels of Drp1,NLRP3 and IL-1 β in the experiment group were significantly lower than those in the model group;ELISA results indicated that the expressions of IL-17A and IL-18 in serum of mice in the experiment group were lower than those in the model group.Taken together,Mdivi-1 can reduce mitochondrial damage and ROS production by inhibiting the expression of Drp1,thereby reducing the production of NLRP3 inflammasome,down-regulating IL-1 β,IL-18 and IL-17A,and alleviating the IMQ-induced psoriasis-like skin inflammation in mice.

BackgroundIn China， the structure shift from just one-child family to both one-child and more-than-one-child families is happening. Exploring how the sibling relationships effect between adolescent personality impulsivity and aggressivity is of great significance for promoting adolescent mental health as well as maintaining social harmony and stability. ObjectiveTo investigate the effecting path of sibling relationships between personality impulsivity and aggressivity in adolescents， so as to provide references for the prevention of violent and aggressive behavior in adolescents. MethodsFrom February to April， 2023， a total of 1 200 students with sibling relationships from 12 primary and secondary schools in a county of Sichuan province were included by random sampling. Barratt Impulsivity Scale （BIS-11）， Chinese Version of Buss & Perry Aggression Questionnaire （AQ-CV）， and Sibling Relationship Questionnaire （SRQ） were used for cross-sectional investigation. Pearson Correlation Analysis was used to analyze the correlation between the scores of these scales. Bootstrap method was used to test the effecting path of sibling relationships between personality impulsivity and aggressivity. ResultsThe total score of BIS-11 was positively correlated with that of AQ-CV as well as the scores of conflict and competition dimensions in SRQ （r=0.485、0.276、0.280，P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.383， P<0.01）. The total score of AQ-CV was positively correlated with the scores of conflict and competition dimensions in SRQ （r=0.387， 0.340， P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.304， P<0.01）. Within SRQ， negative correlations could be observed between the score of warmth/intimacy and scores of conflict and competition （r=-0.307， -0.375， P<0.01）， whereas positive correlation could be observed between the score of conflict and that of competition （r=0.267， P<0.01）. The total effect of personality impulsivity level on aggressivity level in adolescent was 0.480 （P<0.01）. Sibling relationships played a mediating role between personality impulsivity and aggressivity in adolescents. Meanwhile， the indirect effect values of warmth/intimacy， conflict and competition were 0.054， 0.075 and 0.062， with the effect values accounting for 11.21%， 15.70% and 12.93%， respectively. ConclusionThe personality impulsivity of adolescents can directly affect their aggressivity， and sibling relationships may act as an important channel connecting personality impulsivity and aggressivity. ［Funded by 2023 Project of the Psychology and Behavioral Science Research Center of the Deyang Federation of Social Sciences （number， XLYXW2023305）］

Objective To evaluate the effect of the 3D-printed heart model on congenital heart disease (CHD) education through systematic review and meta-analysis. Methods The literature about the application of the 3D-printed heart model in CHD education was systematically searched by computer from PubMed, Web of Science, and EMbase from inception to November 10, 2022. The two researchers independently screened the literature, extracted data and evaluated the quality of the literature. Cochrane literature evaluation standard was used to evaluate the quality of randomized controlled trials, and JBI evaluation scale was used for cross-sectional and cohort studies. Results After screening, 23 literatures were included, including 7 randomized controlled trials, 15 cross-sectional studies and 1 cohort study. Randomized controlled trials were all at low-risk, cross-sectional studies and and the cohort study had potential bias. There were 4 literatures comparing 3D printing heart model with 2D image teaching and the meta-analysis result showed that the effect of 3D printing heart model on theoretical achievement was more significant compared with 2D image teaching (SMD=0.31, 95%CI –0.28 to 0.91, P=0.05). Conclusion The application of the 3D-printed heart model in CHD education can be beneficial. But more randomized controlled trials are still needed to verify this result.

Objective To investigate the basic situation and occupational health conditions of nuclear medicine radiation workers in Jiangsu Province based on the research protocol developed by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences for the nationwide study on the health effects of nuclear medicine radiation in China, understand the impact of occupational radiation on the physical health of nuclear medicine radiation workers, and provide a basis for improving the occupational protection of nuclear medicine radiation workers and reducing the risk of occupational radiation-related health issues. Methods A census approach was used to collect general data and occupational health information of nuclear medicine radiation workers in Jiangsu Province. The analysis focused on the abnormalities in physical examination indicators among radiation workers of different genders, ages, and working years to evaluate the health effects of occupational radiation exposure. Results The occupational health examination data of 472 nuclear medicine radiation workers were collected from 76 medical institutions in Jiangsu Province. The results showed that the detection rate of abnormal hypothyroidism in female workers (8.90%) was higher than that in male workers (2.54%) (P=0.028). With increasing working years, the detection rates of cataract and continuous decrease in white blood cell count increased (P＜0.001). The multivariate logistic regression identified working years as a risk factor for cataract and continuous decrease in white blood cell count (OR=1.59, 95%CI=1.40-3.35, P=0.0003; OR=4.15, 95%CI=3.11-29.91, P=0.0001). In addition, working years was also a risk factor for hypertension, fatty liver, and tumor (OR=2.28, 95%CI=1.51-3.47, P=8.76 × 10⁻⁵; OR=1.69, 95%CI=1.10-2.58, P=0.0145; OR=2.04, 95%CI=1.00-4.16, P=0.0469). Conclusion The study found that working in nuclear medicine could increase the risk of various radiation-related diseases, and the risk is influenced by factors such as working years.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.