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

AIM: To investigate the correlation between axial length and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus.METHODS:This study is a cross-sectional study. A total of 53 cases(104 eyes)of type 2 diabetes patients who admitted to the ophthalmology department of the Jining No.1 People's Hospital between January and May 2023 were included. Among these cases, 51 patients had both eyes included, while 2 patients had only one eye included. The patients were divided into two groups based on the presence or absence of fundus lesions. The non-diabetic retinopathy(NDR)group consisted of 32 eyes, and the DR group consisted of 72 eyes. Within the DR group, the patients were further categorized based on the severity of fundus lesions. The non-proliferative diabetic retinopathy(NPDR)group comprised of 27 eyes, and the proliferative diabetic retinopathy(PDR)group consisted of 45 eyes. The axial lengths of eyes in the DR group were divided into four groups using quartiles: 19 eyes in the 20.00～22.09 mm group, 17 eyes in the 22.10～22.70 mm group, 18 eyes in the 22.71～23.12 mm group, and 18 eyes in the 23.13～24.48 mm group. Binary Logistic regression analysis was employed to investigate the factors influencing the occurrence of DR and PDR.RESULTS:Binary Logistic regression analysis showed that both axial length and age significantly influenced the development of DR and PDR.(Axial length: OR=0.296, 95%CI:0.130～0.672, P<0.05; OR=0.237, 95%CI:0.076～0.736, P<0.05; age: OR=0.949, 95%CI:0.907～0.994, P<0.05; OR=0.879, 95%CI: 0.820～0.942, P<0.05). The risk of PDR in the group with axial length of 23.13～24.48 mm was reduced compared to the group with axial length of 20.00～22.09 mm(OR=0.057; 95%CI: 0.006～0.515, P=0.011).CONCLUSION:The findings indicate that longer axial length in patients with type 2 diabetes are associated with a decreased risk of developing DR, as well as a reduced likelihood of DR progressing to PDR. Therefore, a long axial length can be considered a protective factor against DR.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To summarize the application experience and the therapeutic effect of Nirmatrelvir-Ritonavir (trade name: Paxlovid) for COVID-19 in children. Methods: A retrospective analysis was performed on the clinical data, including collecting the clinical manifestations and clinical outcomes, dynamically monitoring the blood routine, hepatic and renal function and SARS-CoV-2 nucleic acid results, and observing the related side effects during the treatment, etc, of 3 cases with COVID-19 treated with Paxlovid admitted to Shanghai Children's Hospital (designated referral hospital for SARS-CoV-2 infection in Shanghai) from May 1^st to June 1^st, 2022. Results: The 3 cases were 12, 14, 17 years of age, among which 2 cases were males, 1 case was female. All 3 cases were mild cases with underlying diseases and risk of developing into severe COVID-19, with symptoms of high fever, sore throat and dry cough. The treatment of Paxlovid at 3^rd day of symptom onset contributed to the symptom-free after 1-2 days and negative results of SARS-CoV-2 nucleic acid after 2-4 days. All patients had no adverse manifestations of gastrointestinal tract and nervous system but a case had little skin rashes, which recovered after the withdrawal of Paxlovid. Three cases had normal hepatic and renal function during the Paxlovid treatment. At 3 months after discharge, no clinical manifestations of post-COVID syndrome were found in all 3 cases. Conclusion: Paxlovid was effective and relatively safe in the treatment of 3 children with COVID-19.
Child ; Male ; Humans ; Female ; COVID-19 ; SARS-CoV-2 ; Ritonavir/therapeutic use* ; Retrospective Studies ; China ; Nucleic Acids ; COVID-19 Drug Treatment

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Aloin is a small-molecule drug well known for its protective actions in various models of damage. Traumatic brain injury (TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier (BBB) often leads to an adverse prognosis. Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear, we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models. Adult male C57BL/6 mice underwent controlled cortical impact injury, and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury, then both received aloin treatment. In the animal experiments, we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema, decrease disruption of the BBB, and improve neurobehavioral performance after cortical impact injury. In the cellular studies, the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury. The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase, the activation of p65 nuclear factor-kappa B, and the ratios of B cell lymphoma (Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3. We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells. Aloin may thus be a promising therapeutic drug for TBI.

Objective: To investigate the regularity in and risk factors for perioperative deep venous thrombosis (DVT) and the changes in plasma D-dimer in patients with tibiofibular fracture. Methods: A retrospective analysis was done of the 180 patients with tibiofibular fracture who had been treated at Department of Orthopaedics and Trauma, Xi'an Honghui Hospital from September 2014 to February 2018. They were 114 males and 66 females, aged from 16 to 83 years (average, 47.6 years). The levels of plasma D-dimer were detected at admission, one day preoperation, and 1, 3, 5 days postoperation. B-ultrasound examination of both lower extremities was performed before and after surgery. According to the results of B-ultrasound, the patients were divided into a DVT group and a non-DVT group. The 2 groups were compared in the plasma D-dimer levels measured at different time points. DVT risk factors were screened by univariate analysis, and multivariate logistic regression analysis was used to determine independent risk factors. Results: Of this cohort, 54 cases (30%) developed DVT and 39 cases (21.7%) did preoperation. Of the 39 cases (mixed DVT in one and distal DVT in 38 ones), DVT disappeared in 14 postoperation. Of the 40 cases (22.2%) of postoperative DVT (proximal DVT in one, mixed DVT in one and distal DVT in 38 ones), 15 developed newly postoperation. Multivariate logistic regression analysis showed that age, time from injury to operation, pre-operative and postoperative D-dimer elevation were independent risk factors for DVT in the patients. The D-dimer levels in the DVT group were significantly higher than in the non-DVT group at one day preoperation, and 1, 3, 5 days postoperation (P<0.05). The area under the receiver operating characteristic curve was 0.704. When the critical value of D-dimer was 1.4 mg/L, its sensitivity for DVT diagnosis was 0.944 and its specificity 0.246 (poor). When the concentration of D-dimer was 4.45 mg/L, its sensitivity for DVT diagnosis was 0.574 and its specificity 0.817 (the highest). Conclusions Perioperative DVT may happen in patients with tibiofibular fracture, mostly at the distal end beyond the popliteal vein. Clinically, patients who are advanced in age, have plasma D-dimer elevation at admission and after operation, and have waited long for operation should be alert to the occurrence of DVT. The plasma D-dimer level with a recommended threshold of 4.45 mg/L may have a certain diagnostic value for patients with tibiofibular fracture.

Objective: To explore the role of D-dimer level in patients with acute exacerbation of chronic obstructive disease (AECOPD) in predicting the re-admission of patients. Methods: One hundred and twenty chronic obstructive pulmonary disease (COPD) patients in the Shanghai General Hospital of Shanghai Jiao Tong University form January 2016 to December 2018 were divided into AECOPD group (62 cases) and stable COPD group (58 cases).The level of serum D-dimer was analyzed and Pearson correlation analysis was performed with the patient′s blood gas analysis and COPD assessment test (CAT) score. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum D-dimer level for readmission. Results: Serum D-dimer level was significantly higher in AECOPD group than that in stable group: (1.24 ± 0.56) mg/L vs. (0.39 ± 0.22) mg/L, and there was statistical difference (P<0.01). Serum D-dimer level was negatively correlated with PaO₂ in COPD patients (r = 0.712, P = 0.000), but positively correlated with PaCO₂ (r = 0.683, P = 0.000) and CAT score (r = 0.652, P = 0.000). The area under the ROC curve of D-dimer level to re-admission of COPD patients within one year was 0.848. The cutoff value was 1.015 mg/L. Conclusions The level of D-dimer in COPD patients is of great value in predicting the re-admission of patients, which can be used as an independent indicator of disease progression.

BackgroundImmunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.

MethodsWe performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC) and Tac Cwere measured at the 1 week and the 1 month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.

ResultsThe occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC at the 1 week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUClevel was <30 mg·h·L at the 1 week (15.0% vs. 44.4%) or the Tac Cwas <4 ng/ml at the 1 month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC at the 1 week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac Cat the 1 month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05).

ConclusionsLow-level exposure of MPA and Tac Cin the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC <30 mg·h·L and Tac C <4 ng/ml should be avoided in the first few weeks after transplantation.

Adult ; Female ; Graft Rejection ; immunology ; prevention & control ; Humans ; Immunosuppressive Agents ; chemistry ; therapeutic use ; Kidney Transplantation ; adverse effects ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; chemistry ; therapeutic use ; Retrospective Studies ; Tacrolimus ; chemistry ; therapeutic use ; Time Factors

Objective To study long term renal function of Donation after citizen's deceased transplantation.Methods We compared the data of 38 subjects who got Delayed Graft Function(DGF) with 80 Immediate Graft Function (IGF) subjects underwent DCD transplantation in our hospital before June 2016.Evaluated the renal function by detecting the serum creatinine (sCr),the estimating glomerular filtration rate (eGFR) calculated with MDRD formula and urine protein at the 1,2,3 year post transplantation.Results Analyzed the serum eGFR of two groups,there was no significant differences at 1 and 2 year post transplantation,sCr of two groups showed no significant differences at 3 year (P =0.053)post transplantation,eGFR of two groups showed significant differences at 3 year (P =0.042)post transplantation and positive incidence of urine protein showed significant differences at 2 year (P =0.028)and 3 year (P =0.037)post transplantation.Conclusion DGFoccuring after DCD transplantation had an effect on long term renal function,.mainly on reducing of eGFR and increasing of urine protein positive rate 2 or 3 years after transplant.