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 explore the epidemiological features and relational factors of accidental death among children under 5 years of age in rural area of Shaanxi Province. 【Methods】 A case-control study was conducted in the research, and children under 5 years old in nine National surveillance counties of Shaanxi were collected. The questionnaire of national survey of accidental injuries among children under 5 years of age was used to investigate the basic information of children, socio-demographic characteristics, child care status, injury occurrence condition. The mean, standard deviation and percentage were used to describe the basic situation and main characteristics of accidental death. The Chi-square test and Logistic regression methods were performed to explore the relational factors of accidental death of children. 【Results】 Of the 25 cases of accidental death of children under the age of five years old, 5 were traffic accidents (20.0%), 9 cases were falling (36.0%), and 11 were suffocation (44.0%). Age distribution showed that children of accidental suffocation were younger, with 90.9% (10 cases) of them under the age of 1 years old. Gender distribution showed that traffic accident deaths occurred to boys. Area distribution showed that falling and suffocation death mainly happened in Hanzhong, while traffic accidents death mainly in Weinan. When the accident happened, 8 caregivers were not on the scene. What was worse, among 17 caregivers who were on the scene of accident, only 4 kept an eye on children. Compared with 25 children in control group, 16 in case group had received health examination, and the difference showed statistical significance (χ²=8.672, P=0.003). Meanwhile, 9 main caregivers were mothers in the case group, compared with 14 in the control group. The Logistic regression analysis showed that compared with fathers, mothers as the children’ main caregivers could positively reduce accidental death of children (OR=0.016, 95% CI: 0.000 3-0.997, P=0.049). 【Conclusion】 To decrease the incidence rate and mortality of accidental death of children under the age of five years old, parenting behavior guidance, health examination, and targeted health education should be taken in Maternal and Child Health Care System as a routine work.

OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.

Objective:To explore the medication rules of Professor Wang Pei in the treatment of colon cancer.Methods:The medical records of Professor Wang Pei's outpatient treatment for colon cancer were collected, entered into the Traditional Chinese Medicine Inheritance Computing Platform V3.0, and the laws of the prescription's nature, flavor, meridian, drug frequency, drug combination, association rules, and cluster analysis were explored.Results:A total of 65 prescriptions were collected, including 150 Chinese materia medica. The medicinal properties of these Chinese materia medica are mainly warm, cold and flat, the tastes were mainly sweet, bitter and pungent, and the meridians were mainly liver, spleen and kidney meridians. Dampness category and blood circulation promoting and blood stasis category were mainly used, and the most frequently used drugs include Poria, Polyporus, Scutellariae Barbatae Herba, Astragali Radix, Curcumae Rhizoma, and the pairs of Polyporus- Poria, Astragali Radix- Astragali Radix Praeparata cum Melle, Scutellariae Barbatae Herba- Curcumae Rhizoma. Twenty nine high-related drug pairs were obtained from association rules, including Polyporus- Astragali Radix Praeparata cum Melle- Astragali Radix, Poria- Scutellariae Barbatae Herba- Polyporus, Scutellariae Barbatae Herba- Curcumae Rhizoma- Polyporus. The cluster analysis showed the combination of 6 types of medicines mainly focuses on strengthening the spleen and removing dampness, nourishing qi and promoting blood, clearing heat and detoxifying, and astringing the intestines to stop bleeding. Conclusion:Professor Wang Pei mostly discusses the treatment of colon cancer from "spleen dampness, rectification deficiency, heat toxin, blood stasis, bleeding", and the treatment is "invigorating the spleen and removing dampness, invigorating Qi and strengthening the body, clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, and astringent intestines to stop bleeding", which is in line with the thought of Traditional Chinese Medicine treatment of tumors, strengthening the righteousness and eliminating pathogenic factors, and and can be used for clinical reference.

Periodontitis is closely related to many systemic diseases. Cancer of the digestive system is a common malignant tumor. Increasing evidence has shown that periodontitis is related to various digestive system cancers. This review summarizes the current research on the relationship between periodontitis and esophageal cancer, gastric cancer, and colorectal cancer and analyzes the possible mechanisms, including via microorganisms, immunity, inflammation, and genes. The content of periodontal pathogens and Helicobacter pylori in the mouth of patients with periodontitis is increased, with the secretion of many virulence factors and pathogenic enzymes and inhibition or evasion of the host’s non-specific immune function, making the digestive system organs connected to the oral cavity more vulnerable to cancer cell invasion. The plasma levels of interleukin-1β(IL-1β) , interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in patients with periodontitis and digestive system cancers are increased. These elevated factors promote the occurrence and development of cancer by activating endothelial cells, increasing the expression of adhesion molecules and inducing the production of matrix metalloproteinases. Additionally, formyl peptide receptors involved in the inflammatory response and NF-κB, as therapeutic targets of periodontitis, are associated with many cancers, but the mechanism is unclear. Periodontal health is considered a breakthrough point to provide a reference for the prevention and treatment of patients with these three common cancers of the digestive system.

Objective:To explore the clinical effect of hyperbaric oxygen combined with proximal femoral nail anti-rotation (PFNA) internal fixation in patients with femoral intertrochanteric fracture, and to analyze its effect on hemorheology indexes, fracture healing, and joint function.Methods:A total of 92 patients with femoral intertrochanteric fracture admitted to Zibo Branch of CPLA No.960 Hospital from June 2018 to June 2019 were selected as the research subjects and randomly divided into control group ( n=46) and observation group ( n=46). Patients in both groups were treated with PFNA internal fixation and conventional anti-infection treatment, while the patients in the observation group were additionally treated with hyperbaric oxygen. The clinical efficacy, hemorheological indexes, bone density, and bone healing status of the two groups were observed. And the patients’ postoperative function of the hip joint was also assessed. Results:After the treatment, the blood viscosity, erythrocyte aggregation index, and erythrocyte sedimentation rate in the observation group were all lower than those in the control group, and all the differences were statistically significant ( P<0.05). And the fibrinogen level was significantly higher than that in the control group ( P<0.05). Bone mineral density and fracture healing status in the observation group were -2.15±0.13, 73.91% and -1.96±0.10, 93.48% after 3 and 6 months of treatment respectively, which were better than those in the control group -2.30±0.16, 54.35% and -2.11±0.14, 82.61%( P<0.05). The clinical effective rate of the observation group (91.30%) was significantly higher than that in the control group (76.09%) with statistically significant difference ( P<0.05). The postoperative function of hip joint was also significantly improved than that of the control group ( P<0.05). Conclusion:The clinical efficacy of the hyperbaric oxygen combined with PFNA internal fixation in the treatment of femoral intertrochanteric fracture was significant. It can improve postoperative hemorheology indexes, increase bone density and fracture healing rate, and improve the function of hip joint. It is worthy of clinical promotion and application.

Objective:To explore the clinical effect of hyperbaric oxygen combined with proximal femoral nail anti-rotation (PFNA) internal fixation in patients with femoral intertrochanteric fracture, and to analyze its effect on hemorheology indexes, fracture healing, and joint function.Methods:A total of 92 patients with femoral intertrochanteric fracture admitted to Zibo Branch of CPLA No.960 Hospital from June 2018 to June 2019 were selected as the research subjects and randomly divided into control group ( n=46) and observation group ( n=46). Patients in both groups were treated with PFNA internal fixation and conventional anti-infection treatment, while the patients in the observation group were additionally treated with hyperbaric oxygen. The clinical efficacy, hemorheological indexes, bone density, and bone healing status of the two groups were observed. And the patients’ postoperative function of the hip joint was also assessed. Results:After the treatment, the blood viscosity, erythrocyte aggregation index, and erythrocyte sedimentation rate in the observation group were all lower than those in the control group, and all the differences were statistically significant ( P<0.05). And the fibrinogen level was significantly higher than that in the control group ( P<0.05). Bone mineral density and fracture healing status in the observation group were -2.15±0.13, 73.91% and -1.96±0.10, 93.48% after 3 and 6 months of treatment respectively, which were better than those in the control group -2.30±0.16, 54.35% and -2.11±0.14, 82.61%( P<0.05). The clinical effective rate of the observation group (91.30%) was significantly higher than that in the control group (76.09%) with statistically significant difference ( P<0.05). The postoperative function of hip joint was also significantly improved than that of the control group ( P<0.05). Conclusion:The clinical efficacy of the hyperbaric oxygen combined with PFNA internal fixation in the treatment of femoral intertrochanteric fracture was significant. It can improve postoperative hemorheology indexes, increase bone density and fracture healing rate, and improve the function of hip joint. It is worthy of clinical promotion and application.

Objective: To compare the prevalence of dental caries and periodontal disease in patients with end-stage renal disease treated with maintenance hemodialysis with that in healthy controls and to investigate the relationship between end-stage renal disease, dental caries and periodontal disease. Methods : A total of 82 maintenance hemodialysis patients who met the inclusion criteria were selected as the case group, and 86 healthy persons who underwent oral examination in the physical examination center were selected as the control group. Dental caries and periodontal conditions were examined in the two groups. The dental caries examination was conducted by determining the number of decayed-missing-filled teeth, which was recorded as recommended by the World Health Organization. The periodontal condition parameters included the plaque index, calculus index, bleeding on probing, periodontal pocket depth and clinical attachment loss. Results: The prevalence of dental caries in the case group and healthy control group was 87.8% and 81.4%, respectively, and there was no statistically significant difference between the two groups (P > 0.05). The periodontal indexes, including the plaque index, calculus index, probe bleeding index, periodontal pocket depth and clinical attachment level, in the case group were significantly higher than those in the control group (P < 0.05), and the prevalence of periodontitis in the case group was significantly higher than that in the control group (97.6% vs 88.4%, P < 0.05). Conclusion The dental caries conditions were comparable between the case group and the control group, but the prevalence and severity of periodontitis were significantly higher in the case group than in the control group.

Objective: To investigate the efficacy and outcome of transcatheter patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS). Methods: Sixty consecutive patients with cryptogenic stroke who undertook transcatheter PFO closure between May 2015 and September 2017 in Beijing Tiantan Hospital were enrolled in this prospective study.Transcranial Doppler (TCD) bubble test was performed and right-left shunt(RLS) was confirmed in all patients.Closure success rate,effective closure rate, complications, recurrence of ischemic stroke and new onset atrial fibrillation were evaluated. Results: A total of 60 patients (42 male,age range 24-68 (47±11)years) were included in the study.PFO size (motionless state) was (1.6±0.6)mm.RLS before closure was graded and 11 patients had moderate RLS and 48 patients had large RLS (include 41 patients who experienced shower or curtain effect).Closure success rate was 100% (60/60).No severe complications were observed.At 6 months,45 patients completed TCD bubble test.Of these, 4 patients suffered from moderate to large residual and thus effective closure rate was 91%(41/45).The mean follow-up period was 2-29 (median 12) months. During the follow-up, only 1 patient experienced recurrent cerebral infarction.New onset atrial fibrillation was not detected. Conclusion Transcatheter PFO closure is effective,safe and related with a good outcome in reduction of recurrent CS for patients with PFO.

Purpose To observe the impact of sleep deprivation (SD) for 24 hours on human brain regional homogeneity (ReHo) by using functional magnetic resonance imaging (fMRI),and briefly discuss the intervening effect of transcranial direct current stimulation (tDCS) on ReHo after SD.Material and Methods Sixteen healthy individuals were enrolled,and self-controlled study were adopted.Resting-state fMRI scans were performed in wakefulness,after SD,and after tDCS (true or placebo stimuli).The ReHo analysis approach was employed to calculate the ReHo values of whole brain in different states.The differences between before and after SD,and between true and false tDCS after SD,were analyzed.Results Compared with wakefulness,SD mainly enhanced ReHo in brain regions of left precentral gyrus,right precentral gyrus,bilateral temporal lobe and thalamus,but decreased ReHo in brain regions of right precuneus,left superior occipital gyrus,limbic lobe and bilateral angular gyrus,superior frontal gyrus,middle frontal gyrus.Compared with placebo stimuli,the true tDCS enhanced ReHo in brain regions of bilateral precuneus,angular gyrus and right forehead,superior middle gyrus,but decreased ReHo in brain regions of the medial side of left frontal lobe,right precentral gyrus,parahippocampal gyrus,substantia nigra and bilateral temporal lobe,pons and so on.Conclusion SD can cause ReHo change in a large number of brain regions.The tDCS on the prefrontal cortex improves the brain regions with ReHo reduction caused by SD.The improved brain regions mainly include bilateral precuneus/posterior cingulate cortex.Therefore,tDCS on the prefrontal cortex can improve brain dysfunction caused by SD.