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 investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

OBJECTIVE To investigate the levels of high-mobility group box 1(HMGB1)protein,soluble fms-like tyrosine kinase 1(sFLT-1)and lactate-to-albumin ratio(LAR)in patients with severe pulmonary infection-associ-ated sepsis undergoing continuous renal replacement therapy(CRRT),and their correlation with 28-day clinical outcomes.METHODS A total of 102 patients with severe pulmonary infection-associated sepsis undergoing CRRT admitted to the People's Hospital of Nanchuan Chongqing from Jul.2021 to Jul.2024 were enrolled.Based on 28-day clinical outcomes,they were divided into a favorable prognosis group(71 cases)and a poor prognosis group(31 cases).The levels of HMGB1,sFLT-1,lactate,albumin and LAR were compared between the two groups.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of HMGB1,sFLT-1 and LAR for 28-day clinical outcomes in patients with severe pulmonary infection-associated sepsis undergoing CRRT.RESULTS Gram-negative bacteria were the predominant pathogens in patients with se-vere pulmonary infection-associated sepsis undergoing CRRT.The poor prognosis group had higher lactate levels(4.01±1.07 mmol/L)and lower albumin levels(27.46±4.15 g/L)than the favorable prognosis group(P＜0.05).The levels of HMGB1(62.66±15.66 ng/ml),sFLT-1(0.71±0.17 ng/ml)and LAR(14.59±3.64％)in the poor prognosis group were significantly higher than those in the favorable prognosis group(P＜0.05).The combined detection of HMGB1,sFLT-1 and LAR yielded an area under the curve(AUC)of 0.949 for predicting poor 28-day mortality in patients with severe pulmonary infection-associated sepsis undergoing CRRT,superior to the single detection of the indexes(P＜0.05),with a sensitivity of 93.55％and specificity of 87.32％.CONCLUSIONS In patients with severe pulmonary infection-associated sepsis undergoing CRRT,gram-negative bacteria are the predominant pathogens.Patients with poor prognosis exhibit abnormally elevated levels of HMGB1,sFLT-1 and LAR,and the combined detection of these three markers demonstrates high predictive value for 28-day mortality.

Objective: To investigate the clinical features and prognostic factors of gastric cancer patients under the age of 40. Methods : The clinical data of 126 young gastric cancer patients under the age of 40 were retrospectively analyzed. Log⁃Rank test and Cox regression model were used to analyze prognostic risk factors ,respectively. Results: The average age of gastric cancer patients in our group was 33. 6 years ,and there were more female patients than male patients(female ∶ male = 1. 25 ∶ 1) , Upper abdominal pain and fullness discomfort were the most common clinical manifestations ,and the predominant sites were gastric antrum angle (43. 7% ) and gastric body (42. 9% ) . Lauren type was mainly diffuse type (89. 7% ) , Nakamura type was mainly undifferentiated type (91. 3% ) , and WHO type was the most common type of low⁃adherence carcinoma (46. 8% ) . 71. 4% of patients were diagnosed with advanced 46. 7% , respectively. The results of univariate analysis showed that the levels of serum CA199 ,tumor length ,depth of tumor invasion ,lymphatic metastasis ,vascular invasion ,and surgical approach were risk factors affecting the prognosis of patients. Multivariate analysis revealed that the levels of serum CA199 ,the depth of tumor invasion and surgical approach were independent prognostic factors. Conclusion Young gastric cancer has a high degree of malignancy and strong biological invasiveness. Most patients are diagnosed at the advanced stage of the tumor,and the overall prognosis is poor. The levels of serum CA199 ,the depth of tumor invasion and surgical approach were independent prognostic factors.

Objective:To evaluate the clinical efficacy and safety of fecal microbiota transplantation(FMT)for the treatment of chronic functional constipation in the elderly.Methods:A total of 33 elderly patients with chronic functional constipation were included and given three sessions of FMT.Changes in fecal characteristics, constipation, mood and quality of life in these patients were evaluated using the Bristol stool form scale(BSFS), the constipation assessment scale(CAS), patient assessment of constipation symptoms(PAC-SYM), the Zung self-rating anxiety scale(SAS), the Zung self-rating depression scale(SDS), and the patient assessment of constipation quality of life(PAC-QOL)before and 12 weeks after treatment.The clinical efficacy was based on comparison between pre-and post-treatment results for each patient.Results:Clear improvement was achieved in 33 patients 12 weeks after treatment, compared with before transplantation.Post-treatment scores of the constipation assessment scale and symptom self-assessment questionnaire for patients with constipation were(8.9±1.2)scores and(26.5±2.4)scores, respectively, significantly lower than pre-transplantation scores of(12.2±1.1)scores and(32.4±2.4)scores( t=15.034, 13.904, both P<0.001). Similarly, post-treatment scores were also lower than pre-transplantation levels for the self-rating anxiety scale[(50.4±8.4)scores vs.(57.5±9.0)scores, t=10.333, P<0.001], the self-rating depression scale[(50.6±8.4)% vs.(55.0±10.5)%, t=5.301, P<0.001], and self-assessment questionnaire for quality of life[(88.2±7.3)scores vs.(103.7±7.3)scores, t=23.300, P<0.001]. Conclusions:FMT can improve fecal characteristics and constipation symptoms, relieve anxiety and depression, improve the quality of life, and provide a new option for the treatment for elderly patients with chronic functional constipation.

Objective:To explore the clinical value of the geriatric potentially inappropriate medication(PIM)evaluation system in elderly inpatients.Methods:As a prospective cohort study, 203 elderly inpatients with polypharmacy were randomly divided into the control group and experimental group.Geriatric PIM evaluation system(based on the criteria for judging potential inappropriate drug use in Chinese elderly 2017 edition)on wechat platform was applied to patients of experimental group.During the 6 months, the number of elderly syndromes, types of drugs, the days in hospitalization, readmission rates and all-cause mortality were compared between two groups.Results:The age of 203 elderly inpatients ranged from 60 to 94(77.30±10.34)years, including 121 males and 82 females.The morbidity proportion of top five diseases were 69.95%(142/203)in cerebral infarction(non-acute phase), 62.07%(126/203)in hypertension, 24.14%(49/203)in coronary heart disease, 9.85%(20/203)in atrial fibrillation, and 6.40%(13/203)in cardiac insufficiency.The 97.53%(198/203)of elderly hospitalized patients had at least one senile syndrome, the average was 4.3±2.0.Insomnia, fall and frailty accounted for 32.87%(15/198), 28.45%(56/198)and 13.66%(27/198)respectively.Compared with the control group, the average length of stay in hospital in the experimental group significantly decreased[(16.38±4.29) vs.(21.32±6.10)d, t=2.438、 P=0.025], the number of senile syndrome, the score of fall, weakness and the re-admission rate were also decreased significantly(3.11±2.14 vs.4.32±1.50, t=0.854、 P=0.032; 6.19±1.35 vs.8.61±3.22, t=4.078、 P=0.044; 3.94±1.92 vs.5.65±1.34, t=2.843、 P=0.038; 9.81%(10/102) vs.1.98%(2/101), χ2=4.772、 P=0.029), and the frequency of PIM was significantly different between two groups(417.36±49.21 vs.210.25±38.23, t=2.136、 P=0.034). Conclusions:After making the drug adjustment on the elderly inpatients with multiple drugs, PIM evaluation system for the elderly are able to reduce the incidence of geriatric syndrome, shorten the length of stay in hospital, improve the rational use of drugs, and enhance the quality of life of the elderly patients.

Objective:To analyze the HIV and HBV coinfection in HIV/AIDS cases who newly received highly active antiretroviral therapy during 2005-2019 in Jiangsu province.Methods:According to the base data of HIV/AIDS cases on HAART enrolled between January 2005 and December 2019; the National Information system was retrospectively collected for HIV/AIDS Control and Prevention of Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. A Chi-square test was used to assess differences in rates of HBsAg testing and HIV/HBV coinfection between potential risk factors. The unconditional logistic regression model entered risk factors with P values <0.05 in the Chi-square test. Results:There were 29 288 HIV/AIDS cases newly received HAART during 2005-2019. The rate of HBsAg test was 49.8% (14 594/29 288) the rate of HBsAg test increased from 0.0% (0/80)to 75.2%(3 448/4 586), showing an increasing trend year by year during 2005 to 2019. Among HIV/AIDS cases tested HBsAg, 81.6% (11 915/14 594) cases were from Jiangsu province; the ratio of male to female was 7.34∶1 (12 845∶1 749), the average age was (38.5±13.8) years old, 96.1% (14 023/14 594) were Han nationality,48.9% (7 131/14 594) of the HIV/AIDS cases married, 97.9%(14 294/14 594) were infected with HIV through homosexual and heterosexual transmission. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases initiated HAART in 2015 or after that, married, not Jiangsu province resident, college education or above, and drug injection infected were more likely to have HBsAg testing. 8.6%(95% CI:8.2%-9.1%) were HBsAg positive. The HIV and HBV coinfection rates were more than 10% before 2016 while showed stability from 6.7% to 8.2% since 2016. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases who were male, elder, married, non-Han, primary education or below were more likely to have HBV coinfection. Conclusion:More HBsAg testing should be strengthened when the HIV/AIDS cases initiated HAART in Jiangsu province, 2005-2019.

Objective:To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review.Methods:The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled.Results:A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk ( RR) = 0.761, 95% confidence interval (95% CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmol·100 mL -1·min -1: -3±3 vs. -11±3, P < 0.05) and glutamine intake (nmol·100 mL -1·min -1: -97±22 vs. -51±13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. Conclusions:Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.

Objective: To investigate the correlation between frailty status and anticoagulation therapy in elderly patients with atrial fibrillation. Methods: A total of 131 atrial fibrillation inpatients in our hospital aged 70 years and over with a mean age of(77.4±6.4)years were enrolled from January 2017 to June 2018 in this retrospective study.According to the state of anticoagulation therapy at discharge, patients were divided into the anticoagulation group(n=67)and the non-anticoagulation group(n=64). Data including gender, age, N-terminal pro-brain natriuretic peptide(NT-proBNP), glomerular filtration rate(eGFR), the type of medication, HAS-BLED(Hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), CHA2DS2-VASc scores, Charlson comorbidity index and clinical frailty scores(CFS)were recorded and compared between the two groups.Spearman correlation was used to analyze the correlation between frailty degrees and program of anticoagulant therapy.Two-class Logistic regression models were used to analyze the related factors for programs of anticoagulant therapy. Results: The incidence of the frailty syndrome was 56.49% in 131 elderly patients with atrial fibrillation.Compared with the anticoagulation group, non-anticoagulation group showed that the CFS score[(5.73±1.85)vs.(3.69±2.07), P<0.05], the incidence of the frailty syndrome(67.19% vs.46.27%, P<0.05)and Charlson index[(6.09±2.80)vs.(4.98±2.61), P<0.05]were increased.While, there was no significant difference in HAB-BLED score and CHA2DS2-VASc score between the two groups(P>0.05). The correlation analysis showed that there was a negative correlation between the application of anticoagulants and CFS grade in elderly patients with atrial fibrillation(r=-0.138, P<0.05). Multivariate Logistic regression analysis showed that age, CFS score and the incidence of frailty state were risk factors in elderly atrial fibrillation patients without the anticoagulant therapy(P<0.05). Conclusions The incidence of frailty state in elderly patients with atrial fibrillation is high, and the proportion of patients receiving the anticoagulant therapy is low.Age and frailty may be the most important influencing factors for anticoagulant therapy.Therefore, it is of great significance to incorporate frailty assessment into the management of anticoagulant therapy in elderly patients with atrial fibrillation.

Objective To investigate the expression and clinical significance of endoplasmic reticulum protein 29(ERp29) in colorectal cancer. Methods Paraffin-embedded sections from 62 cases of colorectal cancer tissues were obtained and used for immunohistochemical staining of ERp29. The clinical and pathological data of various levels of ERp29 in patients with colorectal cancer were analyzed to determine if there was a significant difference. Results The expression of ERp29 in 62 cases of colorectal cancer tissues, 24(38. 7％ ) cases were positive and 38(61. 3％ )cases were negative. The expression of ERp29 in 62 cases of adjacent tissues, 58 (93. 5％ ) cases were positive and 4(6. 5％ ) cases were negative. There was a significant difference in TNM classification and lymph node metastasis between ERp29 positive group and ERp29 negative group (P ＜ 0. 05 ). Conclusion Colorectal cancer tissues have significantly lower levels of ERp29 than adjacent tissues. ERp29 may be helpful to evaluate the metastatic proclivity and prognosis of colorectal cancer.