OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Abstract Serine is a non-essential amino acid that plays a key role in the synthesis of biomolecules such as proteins, nucleotides and lipids, and changes in the uptake, absorption, synthesis and catabolic levels of serine in vivo all affect multiple physiological processes in tissue cells. Serine plays a key role in intracellular energy metabolism and signaling linkages, and has a profound impact on the developmental processes of a variety of metabolic diseases, cancer, neurodegenerative diseases and aging. In-depth study of serine metabolic pathways can provide new targets and strategies for early diagnosis, treatment and prevention of related diseases. Based on the physiological function of serine, this article expounds the synthetic and metabolic transformation of serine in cells, and reviews the research progress of intracellular serine metabolism on cell physiology and related diseases at home and abroad, which provides a theoretical reference for serine metabolism as an emerging target for disease treatment.

[摘 要] 目的：探究SOX9通过上调长链非编码RNA LINC01503的表达对喉鳞状细胞癌（LSCC）细胞的增殖、迁移、侵袭及肿瘤干细胞干性的影响。方法： 常规培养人LSCC细胞AMC-HN-8、TU177、TU212和TU686，用转染试剂将敲减序列及其对照核酸（si-SOX9-NC、si-SOX9#1、 si-SOX9#2、si-LINC01503-NC、si-LINC01503#1、si-LINC01503#2）或过表达质粒及其对照核酸（pcDNA3.1-SOX-NC、pcDNA3.1-SOX-oe、pcDNA3.1-LIN01503-NC和pcDNA3.1-LIN01503-oe）分别转染至TU177细胞或TU686细胞，记为si-SOX9-NC组、si-SOX9#1组、si-SOX9#2组、si-LINC01503-NC组、si-LINC01503#1组、si-LINC01503#2组；pcDNA3.1-SOX9-NC组、pcDNA3.1-SOX9-oe组、pcDNA3.1-LINC01503-NC组、pcDNA3.1-LINC01503-oe组、si-SOX9-NC + pcDNA3.1-LINC01503-NC组和si-SOX9 + pcDNA3.1-LINC01503-oe组。qPCR法检测SOX9 mRNA和LINC01503 在各组细胞中的表达，生物信息学分析SOX9与LINC0503启动子区的结合位点，双萤光素酶报告基因实验和染色质免疫共沉淀实验验证SOX9与LINC01503启动子区是否直接结合，WB法检测SOX9的敲减效率及LINC01503对TU177和TU686细胞干性标志物表达的影响，MTS法检测各组细胞的增殖活力，划痕愈合和Transwell小室实验检测各组细胞的迁移能力，克隆形成实验检测各组细胞的克隆形成能力。结果：SOX9在各种LSCC细胞中呈高表达（均P < 0.05），数据库数据分析显示，在头颈部鳞状细胞癌中，SOX9与LINC01503表达呈正相关（R = 0.12，P = 0.005 9）；SOX9可与LINC01503启动子区直接结合并促进其转录表达（均P < 0.05）；敲减LINC01503可明显抑制TU177细胞的增殖、迁移、侵袭（均P < 0.05），过表达LINC01503明显促进TU686细胞增殖、迁移、侵袭的能力（均P < 0.05），提高TU686细胞克隆形成能力和细胞干性标志物分子CD133、OCT4、SOX2的mRNA和蛋白水平表达（均P < 0.05），敲减LINC01503则均可抑制TU686细胞的克隆形成和细胞干性标志物的表达（均P < 0.05）；敲减SOX9均可明显抑制TU177细胞的增殖、迁移和侵袭能力，降低其干性细胞标志物的表达（均P < 0.05），同时过表达LINC01503则可部分逆转敲减SOX9对TU177细胞恶性生物学行为和干性标志物表达的抑制作用（均P < 0.05）。结论：SOX9和LINC01503在LSCC细胞中呈高表达，SOX9可能通过上调LINC01503表达提高LSCC细胞增殖、转移和侵袭能力和肿瘤干细胞干性。