Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

BACKGROUND:Vascular regeneration,as one of the crucial repair processes after its onset,necessitates visual analysis between the two. OBJECTIVE:To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status,hotspots,and future research trends in this field. METHODS:We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023.The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles,countries,keywords,institutions,authors,citations,and trends. RESULTS AND CONCLUSION:We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field,with the number of published articles continuing to rise.Most of these articles were authored by institutions from China and the United States.Shanghai Jiao Tong University was the most cited institution.The most influential author was Hermann DM,whose article had been cited 1 003 times.The current hot research topics in the field include extracellular vesicles,microRNAs and mesenchymal stem cells,which are being studied for their correlations with relevant diseases.To conclude,the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration,which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration.

Objective To analyze the risk factors for prolonged sedation recovery time in epileptic children.Methods A cross-sectional trial was conducted on the epileptic children who underwent electroencephalography(EEG)with oral administration of chloral hydrate and nasal dexmedetomidine for sedation in our hospital from November 2019 to December 2022.Their general information and sedation and medication data were collected.Prolonged sedation recovery time was defined as beyond the 75th percentile of awaking time,and then the children were divided into recovery time ≤1 h group and＞1 h group.Univariate and multivariable logistic regression analyses were used to identify the risk factors for recovery time in these children.Results A total of 1 346 children were enrolled,including 805 males and 541 females,with a median age of 6.03(4.42,8.56)years.There were 986 children assigned into recovery time ≤1 h group and 360 ones into recovery time＞1 h group.Univariate analysis showed that significant differences were observed in the proportions of age＜1 year(0.8％vs 2.2％,P=0.046),sedation more than 3 times(35.8％vs 42.2％,P=0.031),and treated with multiple antiepileptic drugs(AEDs)(25.5％vs 36.9％,P＜0.001)between the 2 groups.Multivariable logistic regression analysis indicated that age＜1 year(OR=2.943,95％CI:1.063～8.142,P=0.034),sedation times ≥3(OR=1.287,95％CI:1.003～1.649,P=0.047)and multiple use of AEDs(OR=1.718,95％CI:1.325～2.223,P＜O.001)were risk factors for prolonged recovery time.Conclusion Age＜1 year,sedation times ≥3 and multiple use of AEDs are risk factors for prolonged sedation recovery time in epileptic children undergoing EEG after oral chloral hydrate and nasal dexmedetomidine.

AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg

OBJECTIVETo evaluate the orthopedic effect of presurgical nasoalveolar molding (PNAM) devices on the palatal deformities in unilateral complete cleft lip and palate (UCCLP) patients.

METHODSThree groups with 19 patients each were studied. All samples in groups A and B were non-syndromic UCCLP children. Group A was treated with PNAM prior to operation. Group B was untreated prior to operation. Samples in group C were normally developed nose and lip palate infants aged three months. The orthotopic palate photos before and after PNAM treatment for group A, as well as pre-operative photos of groups B and group C, were taken and measured. All statistics were analyzed using SPSS 21.0.

RESULTSPNAM treatment significantly increased the AW, AC, and PA of UCCLP patients (P < 0.05), whereas CPW, CWA, CWAS, CWAH, PMD, and CA significantly decreased (P < 0.05). However, no significant difference was observed with the cases in group C (P < 0.05). The AW, CPW, CA, and PA of the patients in group B significantly increased compared with the cases in group A before PNAM treatment (P < 0.05). Multivariate analysis of variance indicated that TW had no statistically significant difference among the three groups (P > 0.05).

CONCLUSIONPNAM treatment is a non-surgical early treatment for the effective improvement of palatal primary deformities in UCCLP patients.

Alveolar Process ; Child ; Cleft Lip ; Cleft Palate ; Humans ; Infant ; Nose ; Preoperative Care ; Reconstructive Surgical Procedures

Objective To evaluate the orthopedic effect of presurgical nasoalveolar molding (PNAM) devices on the palatal deformities in unilateral complete cleft lip and palate (UCCLP) patients. Methods Three groups with 19 patients each were studied. All samples in groups A and B were non-syndromic UCCLP children. Group A was treated with PNAM prior to operation. Group B was untreated prior to operation. Samples in group C were normally developed nose and lip palate infants aged three months. The orthotopic palate photos before and after PNAM treatment for group A, as well as pre-operative photos of groups B and group C, were taken and measured. All statistics were analyzed using SPSS 21.0. Results PNAM treatment significantly increased the AW, AC, and PA of UCCLP patients (P<0.05), whereas CPW, CWA, CWAS, CWAH, PMD, and CA significantly decreased (P<0.05). However, no significant difference was observed with the cases in group C (P<0.05). The AW, CPW, CA, and PA of the patients in group B significantly increased compared with the cases in group A before PNAM treatment (P<0.05). Multivariate analysis of variance indicated that TW had no statistically significant diffe-rence among the three groups (P>0.05). Conclusion PNAM treatment is a non-surgical early treatment for the effective improvement of palatal primary deformities in UCCLP patients.