Objective:To analyze the pangenome, pan drug resistance genes, pan virulence genes, pan replicons, and others of the plasmids carried by hypervirulent Klebsiella pneumoniae (hvKP) in the world and their evolutionary trends over time, and provide evidence for more comprehensive understanding of the evolution of genetic diversity, drug resistance genes, and virulence genes of the plasmids. Methods:From the National Center for Biotechnology Information database, a total 1 738 plasmids were screened from 524 strains with completed genome sequences in 2 136 strains of hvKP carrying plasmids. Through pangenome, pan drug resistance gene, and pan-virulence gene composition and functional analyses, the curves of pangenome size and new gene size against plasmid isolation time were established, revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results:The homologous genes, homologous drug resistance genes, homologous virulence genes, and replicons of the plasmids carried by hvKP comprised of 12 906, 149, 107 and 89 types, respectively. The fitting curves for the number of new genes, new drug resistance genes and new replicons increased with the increase of plasmids in an open state, while the curve for novel virulence genes was in a closed state. A obvious increase in new drug resistance genes was observed during 2018-2019. Among the newly added drug resistance genes during 2021-2023, beside those conferring aminoglycoside resistance, they were mainly new subtypes conferring carbapenem resistance.Conclusions:The pangenome of plasmids carried by hvKP exhibited high diversity, with the plasmid pan genes, pan drug resistance genes, and pan replicon types gradually expanding, while the pan virulence genes remains stable. The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts, with particular attention to carbapenem resistance.

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective:To analyze the pangenome, pan drug resistance genes, pan virulence genes, pan replicons, and others of the plasmids carried by hypervirulent Klebsiella pneumoniae (hvKP) in the world and their evolutionary trends over time, and provide evidence for more comprehensive understanding of the evolution of genetic diversity, drug resistance genes, and virulence genes of the plasmids. Methods:From the National Center for Biotechnology Information database, a total 1 738 plasmids were screened from 524 strains with completed genome sequences in 2 136 strains of hvKP carrying plasmids. Through pangenome, pan drug resistance gene, and pan-virulence gene composition and functional analyses, the curves of pangenome size and new gene size against plasmid isolation time were established, revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results:The homologous genes, homologous drug resistance genes, homologous virulence genes, and replicons of the plasmids carried by hvKP comprised of 12 906, 149, 107 and 89 types, respectively. The fitting curves for the number of new genes, new drug resistance genes and new replicons increased with the increase of plasmids in an open state, while the curve for novel virulence genes was in a closed state. A obvious increase in new drug resistance genes was observed during 2018-2019. Among the newly added drug resistance genes during 2021-2023, beside those conferring aminoglycoside resistance, they were mainly new subtypes conferring carbapenem resistance.Conclusions:The pangenome of plasmids carried by hvKP exhibited high diversity, with the plasmid pan genes, pan drug resistance genes, and pan replicon types gradually expanding, while the pan virulence genes remains stable. The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts, with particular attention to carbapenem resistance.

Objective:To clarify the definition and attributes of change fatigue among nurses.Methods:A comprehensive literature search was conducted across both Chinese and international databases, including CINAHL, Cochrane Library, Web of Science, PubMed, ProQuest, ScienceDirect, Springer Link, Wanfang Data, China National Knowledge Infrastructure, VIP, and China Biology Medicine disc, from inception to December 2024. Walker and Avant's classic concept analysis method was adopted.Results:A total of 30 relevant studies were included. The defining attributes of nurse change fatigue include perception of change, negative psychological responses, and passive reactions. Antecedents involve personal and organizational factors, and the consequences affect nurses themselves, patients, and the organization.Conclusions:Concept analysis helps clarify the connotation of nurse change fatigue, enabling managers to identify its features and providing a foundation for future targeted interventions to mitigate fatigue and promote nurses' positive responses to organizational change.

Objective:To screen potential comorbid genes shared between inflammatory bowel disease(IBD)and colorectal cancer(CRC),and to explore the relationship between the key gene a disintegrin and metalloprotease 8(ADAM8)and the pathogenesis of IBD and CRC,as well as the underlying mechanisms.Methods:Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database.Differential expression analysis,prognostic gene screening,and intersection analysis were performed to identify shared genes.Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features.Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC.Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression.The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms.The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry(IHC).Results:ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC.ADAM8 was significantly upregulated in both IBD and CRC tissues(all P<0.01),and its high expression was associated with disease progression(P<0.01).CRC patients with high ADAM8 expression had shorter overall survival(OS)(P<0.05 or P<0.01).ADAM8 was also significantly highly expressed in Chinese CRC tissues(P<0.01).Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration,cytokine production,and immune receptor interactions.Additionally,ADAM8 expression positively correlated with immune cell infiltration,including neutrophils and macrophages(P<0.01 or P<0.001).Conclusion:ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis,disease progression,and immune cell infiltration.It holds promise as a common therapeutic target for both diseases.

Objective To investigate the appropriate indicators for monitoring pediatric nociceptive stimu-lation,this study compared the SPI and NOX,two dual-parameter nociceptive stimulation monitors based on different principles,in terms of their effects on remifentanil consumption and postoperative recovery in pediatric adenotonsil-lectomy.Methods Children aged 3～12 years who were scheduled to undergo adenotonsillectomy under general anesthesia with endotracheal intubation were randomly assigned to the conventional group(Group R,n=19),the SPI group(Group S,n=19),and the NOX group(Group N,n=18)according to the type of nociceptive stimu-lation monitor used.All children were subjected to routine fasting.The depth of anesthesia was monitored using a BIS monitor,and the remifentanil infusion rate was adjusted according to heart rate,SPI,or NOX values to maintain the index within the range of 30～50.After surgery,all children were transferred to the Post-Anesthesia Care Unit(PACU)with the tracheal catheter in place until they recovered.During the operation,the consumption of anes-thetics such as remifentanil was recorded.Postoperatively,pain and agitation scores,the incidence of agitation at different time points,the duration of anesthesia,the surgical time,the time to extubation,and the length of stay in the recovery room were measured.Additionally,postoperative adverse reactions and perioperative vital signs were documented.Results In comparison with Group R,in Group N,the intraoperative consumption of remifentanil and the agitation score during the recovery period were significantly reduced.Conversely,in Group S,both of(P<0.05).There were no significant disparities in the FLACC score,the incidence of agitation,and the extubation time among the three groups.Conclusions The NOX index can serve as a quantitative metric for monitoring nonci-ceptive stimulation during pediatric adenotonsillectomy.This index has the potential to decrease the intraoperative consumption of opioids and the residence time in the recovery room.

Objective:To clarify the definition and attributes of change fatigue among nurses.Methods:A comprehensive literature search was conducted across both Chinese and international databases, including CINAHL, Cochrane Library, Web of Science, PubMed, ProQuest, ScienceDirect, Springer Link, Wanfang Data, China National Knowledge Infrastructure, VIP, and China Biology Medicine disc, from inception to December 2024. Walker and Avant's classic concept analysis method was adopted.Results:A total of 30 relevant studies were included. The defining attributes of nurse change fatigue include perception of change, negative psychological responses, and passive reactions. Antecedents involve personal and organizational factors, and the consequences affect nurses themselves, patients, and the organization.Conclusions:Concept analysis helps clarify the connotation of nurse change fatigue, enabling managers to identify its features and providing a foundation for future targeted interventions to mitigate fatigue and promote nurses' positive responses to organizational change.