One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

Objective:To analyze skin manifestations associated with coronavirus disease 19 (COVID-19) in children.Methods:Children diagnosed with COVID-19 accompanied by skin manifestations were retrospectively collected from outpatient clinics or teleclinics at the Department of Dermatology, Children′s Hospital, Capital Institute of Pediatrics from November 1st, 2022 to December 10th, 2022, and their clinical characteristics were analyzed. Analysis of variance was used for comparing measurement data, and Fisher′s exact test for comparing enumeration data.Results:A total of 61 children with COVID-19 accompanied by skin lesions were included, they were aged from 22 days to 17 years (2.83 ± 2.47 years, and their course of disease ranged from 2 to 14 days. Skin lesions manifested as acute urticaria in 25 cases (41.0%), eruptive/maculopapular lesions in 10 cases (16.4%), facial vascular edema in 6 cases (9.8%), urticarial vasculitis in 5 cases (8.2%), pityriasis rosea and erythema multiforme each in 4 cases (6.6%), purpura in 2 cases (3.3%), mixed skin lesions in 2 cases (3.3%), and folliculitis, erythema nodosum, as well as angioedema of the limbs each in 1 case (1.6%). The age of children with different skin manifestations significantly differed ( F = 4.67, P < 0.001). Forty-eight patients (78.69%) presented with generalized skin lesions, while 13 (21.31%) with localized skin lesions; 10 (16.4%) had itching, 3 (4.9%) had a burning sensation, while 48 (78.7%) showed no symptoms. Skin lesions persisted for ≤ 3 days in 36 cases (59.0%) and for > 3 days in 25 cases (41.0%), and all lesions persisted for less than 2 weeks. All 61 patients had fever up to 38.5 ℃; 1 (1.6%) developed skin lesions before the fever, 41 (67.2%) developed lesions during the fever, and 19 (31.2%) developed lesions after the fever. The skin manifestations significantly differed among various groups divided by patients with different lesion distribution, self-reported symptoms, duration of lesions, and sequence between fever and lesion onset (all P < 0.05). No recurrence was observed after recovery, and skin lesions subsided without pigment changes or scaring. Conclusion:COVID-19 was often accompanied by various skin lesions in children, which mainly manifested as urticaria and eruptive/maculopapular lesions.

OBJECTIVE To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia- inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜ 0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）. CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.

Objective:To analyze the cause and epidemiological characteristics of an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province, and to provide scientific basis for anthrax prevention and control.Methods:Using on-site epidemiological investigation methods and the "Anthrax Epidemiological Case Investigation Form", case investigations were conducted based on the epidemiological contact history and close contacts of suspected anthrax cases reported by the national health care system ( n = 83). Scorched skin smears, diseased cattle tissues, soil samples from the slaughter site and smears from slaughter utensils were collected from cases for Real-time PCR testing and pathogenic bacteria isolation and culture, respectively. Anthrax determination criteria were carried out with reference to "Anthrax Diagnosis" (WS 283-2020). Results:A total of 13 cases of cutaneous anthrax were found in this outbreak, including 12 clinically diagnosed cases and one confirmed case (positive Real-time PCR test and isolation of a strain of Bacillus anthracis). The epidemiological investigation determined that the source of infection in this outbreak was diseased cattle, the transmission route was through slaughter of diseased cattle, contact with contaminated utensils and related cattle products, and the patients were mainly engaged in occupations related to cattle slaughter or cattle product collection and sale. A total of 84 samples were collected, including 13 skin scabs, 64 environmental samples and 7 beef samples. Thirty-six positive PCR tests were performed, with a positive rate of 42.86% (36/84). Among them, 100.00% (13/13) were positive for skin scab smear specimens, 29.69% (19/64) for environmental samples and 4/7 for beef samples. A total of 8 strains of Bacillus anthracis were isolated, including 6 environmental specimens, 1 suspected case and 1 beef strain, with an overall detection rate of 9.52% (8/84). Eighty-three close contacts were investigated. Thirteen households involved in the epidemic were disinfected by spraying (200 ml/m 2) with chlorine-containing disinfectant (5 000 mg/L), and a total of 40 households involved in the epidemic were disinfected, covering an area of about 10 765 m 2. Forty-five pieces of suspected contaminated clothing were burned and disposed of, and 152 pieces of kitchenware were soaked. Conclusions:Slaughter of infected cattle, contact with contaminated utensils and related cattle products are the main causes of this skin anthrax outbreak. Strengthening market supervision, deepening inter-animal epidemic prevention, carrying out publicity and education on anthrax prevention and control, and enhancing practitioners' awareness of disease prevention is the key to prevent anthrax from occurring.

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
Humans ; Mycophenolic Acid/adverse effects* ; Azathioprine/adverse effects* ; Tacrolimus/therapeutic use* ; Lupus Nephritis/complications* ; Immunosuppressive Agents ; Treatment Outcome ; Recurrence

Objective:To develop a Beijing norm of Memory and Executive Screening (MES) scale to facilitate its further promotion and application in the future.Methods:Study subjects were selected based on the inclusion and exclusion criteria, including patients who visited the memory clinic of Xuanwu Hospital of Capital Medical University from March 20, 2017 to January 6, 2021, and normal people recruited simultaneously from community, and trained and qualified investigators conducted questionnaire surveys through face-to-face interviews. Then strict quality control, data collection and statistical analysis were performed.Results:A total of 607 participants were included, including 239 normal people, 293 individuals with subjective cognitive decline (SCD), and 75 individuals with mild cognitive impairment (MCI). There was a negative correlation between the scores of MES and age ( r=-0.19, P<0.001), but a positive correlation between scores of MES and education level ( r=0.29, P<0.001). The optimal cut-off value of this scale in Beijing was 86 points, the area under curve (AUC) of the cut-off value to distinguish MCI was 0.847 (normal people vs MCI) and 0.826 (SCD vs MCI), and after adding demographic variables, AUC showed slight increase (0.847 to 0.850 and 0.826 to 0.847), whereas the differences were not statistically significant ( Znormal peoplevsMCI=0.49, ZSCDvsMCI=1.21, P>0.05). And there was no statistically significant difference between MES and Montreal Cognitive Assessment scales in diagnostic power for normal people and people with MCI ( Zscale alone=1.03, Zafter adding demographic variables=1.13, P>0.05). Conclusions:The MES scale has a better distinguishing power for MCI, and its optimal cut-off value in Beijing is 86 points, which is different from previous studies. In the future, the sample size needs to be further expanded to verify this norm.

Objective:To explore the effect of evidence-based nursing practice on the prevention and management of urinary tract infection in patients with radical prostatectomy.Methods:From January 2019 to December 2020, 106 patients with radical prostatectomy who were admitted to the First Affiliated Hospital of Zhengzhou University were selected as the research object by convenience sampling method. The patients were divided into the observation group (53 cases) and the control group (53 cases) by random number table method. The observation group was given evidence-based nursing for the prevention and management of urinary tract infection, while the control group was given routine nursing. The postoperative urinary tract infection incidence and urethral orifice status were compared between the two groups.Results:The incidence of urinary tract infection in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . The urethral orifice state score of the observation group was lower than that of the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The evidence-based nursing applied in the prevention and management of urinary tract infection in patients with radical prostatectomy has an exact effect, which can effectively prevent urinary tract infection and improve the quality of urethral orifice nursing.

Objective:To investigate the role of receptor-interacting protein kinse3 (RIPK3)-mediated necroptosis in diabetic mellitus-caused abolition of cardioprotection induced by sevoflurane postconditioning in rats.Methods:Eighty rats with diabetes mellitus, aged 4-5 weeks, weighing 90-100 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group Sham), myocardial ischemia-reperfusion (I/R) group (group I/R), sevoflurane postconditioning group (group SP) and sevoflurane postconditiong plus RIPK3 inhibitor GSK-872 group (group GSK). Myocardial I/R was induced by 40 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.In group SP, 2.4% sevoflurane was inhaled for 15 min at the beginning of reperfusion.In group GSK, GSK-872 3.3 mg/kg (dissolved in normal saline) was intraperitoneally injected at 24 and 2 h before surgery, and the other treatments were similar to those previously described in group SP.After 120 min of reperfusion, blood samples from the abdominal aorta were collected for determination of concentrations of serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). Myocardial tissues were taken for determination of percentage of myocardial infarct size (by TTC staining) and expression of RIPK3, phospho-Ca 2+ -calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ) and phospho-mixed lineage kinase domain-like protein (p-MLKL) (by Western blot), and the ultrastructure of myocardium was observed by transmission electron microscopy. Results:Compared with group Sham, the serum LDH and CK-MB concentrations and percentage of myocardial infarct size were significantly increased, the expression of RIPK3, p-MLKL and p-CaMKⅡ in myocardial tissues was up-regulated ( P<0.05), and the damage to cardiomyocytes was severe in group I/R.Compared with group I/R, no significant change was found in the parameters mentioned above in group SP ( P>0.05). Compared with group SP, the serum LDH and CK-MB concentrations and percentage of myocardial infarct size were significantly decreased, the expression of RIPK3, p-MLKL and p-CaMKⅡ in myocardial tissues was down-regulated ( P<0.05), and the damage to cardiomyocytes was reduced in group GSK. Conclusion:The mechanism of diabetic mellitus-caused abolition of cardioprotection induced by sevoflurane postconditioning is related to excessive activation of RIPK3-mediated necroptosis in rats.