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As one of the most endangered species, tiger (Panthera tigris) inbreeding has become an urgent issue to address. Using a microsatellite (short tandem repeat, STR) identification system, paternity testing may be helpful to avoid inbreeding in captive breeding programs. In this study, we developed a genome-based identification system named tiger pedigree identification multiplex system (TPI-plex). By analyzing the entire tiger genome, 139,967 STR loci were identified and 12.76% of these displayed three to six alleles among three re-sequenced individual tiger genomes. A total of 204 candidate STRs were identified and screened with a reference population containing 31 unrelated captive tigers. Of these, 15 loci were chosen for inclusion in the multiplex panel. The mean allele number and mean expected heterozygosity (He) were 7.3333 and 0.7789, respectively. The cumulative probability of exclusion (CPE) and total probability of discrimination power (TDP) reached 0.999999472 and 0.999999999999995, respectively. The results showed that the TPI-plex system can be applied in routine pedigree identification for captive tigers. We also added a sex identification marker named TAMEL into the TPI-plex for sex determination.

Abstract Purpose The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. Patients and methods Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients’ baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. Results In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. Conclusion Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

Objective: The previous coronavirus disease 2019(COVID-19) epidemic inflicted significant psychological trauma on emergency and critical care nurses due to various factors, potentially leading to job burnout. Despite the rise of positive psychology, little is known about the post-traumatic growth experience of these nurses after the pandemic. The aim of this study was to assess the experience of post-traumatic growth among emergency and critical care nurses, in order to provide managerial insights for developing effective strategies and facilitating the transformation of nurses' negative emotions into positive ones. Design: A qualitative review. Data sources: PubMed, EBSCO, Medline, Elsvier, Cochrane Library, CINAHL, Web of Science, Embase, and Ovid and Chinese databases include the following: Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), VIP Database and China Biomedical Database (CBM). Review methods: All articles about emergency and critical care nurses’ post-traumatic growth after the COVID-19 pandemic were included after searching and screening 13 databases. The meta-synthesis method was used to integrate and evaluate the included literature in qualitative research. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used as a basis for reporting the review. The literature was selected and evaluated by two researchers, and then meta-integration was used for analysis. Results: From a total of 11 articles, 90 main results were presented, eight new categories were integrated, and three themes were formed: stress period, adjustment period and growth period. These three themes include eight sub-themes: negative emotion, psychological gap, self adjusting, social support, improvement of personal ability, increased sense of professional belonging, spiritual awakening and extended thinking, look ahead. Conclusion: Post-traumatic growth in emergency and critical care nurses is dynamic. Managers should monitor the psychological changes experienced by emergency and critical care nurses following traumatic events, offering targeted support at different stages, providing enhanced professional development opportunities, refining management strategies, guiding nurses in self-adjustment and active coping with trauma, and promoting their physical and mental well-being to ensure a positive mindset for effectively addressing future public health crises.

Objective To qualitatively explore the factors that enhance resilience among emergency nurses (ENs).Design This study is an exploratory qualitative investigation. Semistructured in-depth interviews were used for data collection, while qualitative content analysis was applied for data analysis.Setting A grade A tertiary hospital in Shanghai, China.Participants The study subjects comprised 17 ENs, who were selected using a purposive sampling method.Results Three main themes and the nine subthemes emerged from the study, that is, individual resources, including competency, personality traits and occupational benefits; family resources, including close parent–child attachment and supportive family dynamics; social resources, including peer support, organisational support, resilient leadership and popular support.Conclusion This qualitative study explored the factors promoting resilience among ENs and provided a reference for managers to formulate future management strategies. From the perspective of positive psychology, nurses should receive comprehensive support, focusing on improving their professional accomplishment and role ability while prioritising the development of resilient leadership. These efforts are expected to drive progress and growth across the emergency care team.

Background: Influenced by socio-cultural and world events, Chinese society has significant intergenerational differences. With rapid economic and cultural development, the unique characteristics of Generation Z nursing students in China may influence the clinical education environment. However, the research on Generation Z in China is still in its infancy. Objectives: This study aimed to explore the experiences and perceptions of Generation Z nursing students during their practicum in an intensive care unit (ICU) in the context of China's unique cultural and historical background. Methods: A phenomenological approach was used in this qualitative study. Semi-structured, face-to-face interviews were conducted with fifteen Generation Z nursing students doing practicum in the ICU in a third-level hospital in Shanghai, China. The data were analyzed using Colaizzi's seven-step method. Result: Three themes emerged: intelligent medical services empowering critical care, perception of multiple challenges, and affirmation of the teaching work in the ICU. Conclusions and implications: The clinical instructors should use a combination of online and offline pedagogy, give positive guidance through role modeling, and develop the self-learning skills of Generation Z nursing students. This might help Generation Z nursing students relieve the stress of practicum in the ICU, more quickly adapt to the clinical environment, and enter nursing positions. The result of this research provided valuable information to help clinical practicum programs in China effectively educate Generation Z nursing students. Good education ensures that health care is safe and effective, making it easier for patients to get better.

Objectives This study aims to investigate the post-traumatic growth of emergency nurses (ENs) in Shanghai, China, in 2022 following the COVID-19 pandemic.Design A phenomenological qualitative research approach was employed, with 17 ENs being interviewed between July and August 2022. Data collection was conducted through semistructured, in-depth interviews, and data analysis was carried out using the Colaizzi’s seven-step analysis method.Setting A third-level hospital in Shanghai.Participants A total of 17 ENs were interviewed through face-to-face, semistructured, in-depth interviews.Results Three main themes and eight subthemes were extracted from the data: (a) stress, (b) restructuring and (c) growth.Conclusion Significant stress was imposed on ENs by the Shanghai COVID-19 pandemic, but cognitive restructuring was successfully undergone by them, leading to the experience of growth. It is recommended that post-traumatic growth levels be enhanced through professional psychological counselling and tailored support measures for different stages.

BackgroundDue to the unique work environment, emergency and critical care departments nurses face high job pressure, often resulting in burnout and a high turnover rate. Public health emergencies such as the Corona Virus Disease 2019 pandemic tend to exacerbate these problems further. Therefore, improving the resilience of nurses is crucial to enhance their retention rates.ObjectiveThis systematic review and meta-synthesis of qualitative studies on the resilience of emergency and critical nurses were conducted to provide a reference for clinical managers to develop strategies for improving the resilience of nurses.MethodsFollowing databases were searched for relevant studies: CINAHL Plus, Elsevier, Cochrane Library, Embase, Medline, OVID, Pubmed, Science Direct, LWW and Web of Science, China National Knowledge Network (CNKI), Wanfang Database (CECDB), VIP Database, and Sinomed. Google Scholar and Opengrey were used to search for gray literature. The literature search period was from the establishment of the database to April 2023. The systematic review of qualitative studies followed the Joanna Briggs Institute (JBI) approach, including critical appraisal using the JBI Checklist and synthesis through meta-synthesis. Confidence of evidence was assessed with JBI’s ConQual process.ResultsA total of 12 articles were identified, with 59 main results and 9 new integrated categories. Also, 3 themes, i.e., risk factors, protective factors, and personal growth, and 9 sub-themes, i.e., working pressure, negative emotion, an organizational issue, active learning, sense of occupational benefit, social support, self-cognition and regulation, learn to adapt, and self-actualization, were formed.ConclusionThe resilience of emergency and critical care nurses depends on various factors. Managers should prioritize the mental health of nurses and implement measures to enhance their resilience through social support, team building, and psychological capital development. Additionally, management models can be updated based on domestic and international experience to improve nurses’ job involvement, optimize nursing quality, and promote the advancement of the nursing profession.

BackgroundSepsis stands as a dire medical condition, arising when the body’s immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora’s known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span.MethodsLeveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium.ResultsIn this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029).ConclusionThis research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis’ pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis’ diagnosis, therapeutic interventions, and prognostic assessments.

AimTo investigate the predictive value of C-reactive protein (CRP) to serum albumin (ALB) ratio in the severity and prognosis of acute pancreatitis (AP), and compare the predictive value of the CRP/ALB ratio with the Ranson score, modified computed tomography severity index (MCTSI) score, and Bedside Index of Severity in Acute Pancreatitis (BISAP) score.MethodsThis cohort study retrospectively analyzed clinical data of AP patients from August 2018 to August 2020 in our hospital. Logistic regression analysis was utilized to determine the effects of CRP/ALB ratio, Ranson, MCTSI, and BISAP score on severe AP (SAP), pancreatic necrosis, organ failure, and death. The predictive values of CRP/ALB ratio, Ranson, MCTSI, and BISAP score were examined with the area under the curve (AUC) of the receiver operator characteristic (ROC) curve analysis. DeLong test was used to compare the AUCs between CRP/ALB ratio, Ranson, MCTSI, and BISAP score.ResultsTotally, 284 patients were included in this study, of which 35 AP patients (12.32%) developed SAP, 29 (10.21%) organ failure, 30 (10.56%) pancreatic necrosis and 11 (3.87%) died. The result revealed that CRP/ALB ratio on day 2 was associated with SAP [odds ratio (OR): 1.74, 95% confidence interval (CI): 1.32 to 2.29], death (OR: 1.73, 95%CI: 1.24 to 2.41), pancreatic necrosis (OR: 1.28, 95%CI: 1.08 to 1.50), and organ failure (OR: 1.43, 95%CI: 1.18 to 1.73) in AP patients. Similarly, CRP/ALB on day 3 was related to a higher risk of SAP (OR: 1.50, 95%CI: 1.24 to 1.81), death (OR: 1.8, 95%CI: 1.34 to 2.65), pancreatic necrosis (OR: 1.22, 95%CI: 1.04 to 1.42), and organ failure (OR: 1.21, 95%CI: 1.04 to 1.41). The predictive value of CRP/ALB ratio for pancreatic necrosis was lower than that of MCTSI, for organ failure was lower than that of Ranson and BISAP, and for death was higher than that of MCTSI.ConclusionThe CRP/ALB ratio may be a novel but promising, easily measurable, reproducible, non-invasive prognostic score that can be used to predict SAP, death, pancreatic necrosis, and organ failure in AP patients, which can be a supplement of Ranson, MCTSI, and BISAP scores.

IntroductionAF4/FMR2 family member 4 (AFF4) is a core component of super elongation complex (SEC) and regulates the transcription elongation of many genes. AFF4 depletion or amplification is associated with multiple cancers, but its role in colorectal cancer (CRC) has not been investigated so far.MethodsqRT-PCR and Western blot analyzed AFF4 expression in the paired clinical CRC tissues. The patients’ overall survival curve was determined using the Kaplan-Meier plotter. In vitro experiments, such as cell proliferation, migration, and invasion, were used to preliminarily ascertain the role of AFF4 in CRC. A CRC cell liver metastasis animal model was well established. Livers were harvested and examined histologically by a series of indicators, such as tumor nodules, liver weight, ALT/AST activity, and tumor cell identification by hematoxylin-eosin (HE) staining.ResultsWe firstly examined the expression of AFF4 in colorectal cancer and normal tissues by collecting paired CRC tissues and adjacent normal tissues, revealing that AFF4 was significantly downregulated in CRC patients and lower expression of AFF4 was correlated with poor prognosis. Next, we observed that presence or absence of AFF4 in CRC cells had no effect on cancer cell proliferation, while AFF4 depletion significantly promoted the migration or invasion of CRC cells in vitro. Furthermore, we confirmed that AFF4 deficiency enhanced the metastatic capacity of CRC cells in vivo. Mechanistically, we found that AFF4 upregulated the transcription of CDH1 gene, which encodes E-cadherin and suppresses the epithelial-mesenchymal transition (EMT). Knockdown of AFF4 interfered with CDH1 transcription, resulting in downregulation of E-cadherin expression and the progression of CRC. Moreover, restored CDH1 expression could rescue the phenotype of CRC cells without AFF4.ConclusionsCollectively, our data demonstrated that AFF4 served as a significant novel regulator of CRC via CDH1 transcriptional regulation and a potential effective therapy target for patients with CRC.

Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. Previous studies showed that bovine eNOS serine 1179 (Serine 1177 for human eNOS) phosphorylation enhanced NO synthesis. Meanwhile, heat shock protein 90 (Hsp90) plays a critical role in maintenance of eNOS structure and function. However, the regulatory difference and importance between Serine 1179 phosphorylation and Hsp90 on eNOS activity have not been evaluated. In current studies, S1179D eNOS was employed to mimic phospho-eNOS and exhibited markedly increased enzyme activity than wild type eNOS (WT eNOS). Hsp90 showed a dose-dependent increase for both WT eNOS and S1179D eNOS activity at the presence of all eNOS cofactors, such as Calcium/Calmodulin (Ca2+ /CaM), BH4, and NADPH etc. The enhancement effects were abolished by dominant-negative mutant Hsp 90 protein. ENOS-cofactors dynamic assay showed that Hsp90 enhanced WT eNOS affinity to NADPH, L-arginine, and CaM but not to Ca2+ and BH4. The impact of eNOS Serine 1179 phosphorylation and Hsp90 on eNOS affinity to cofactors has also been compared. Different from the effect of Hsp90 on eNOS affinity to specific cofactors, Serine 1179 phosphorylation significantly increased eNOS affinity to all cofactors. Moreover, VEGF-induced eNOS phosphorylation in bovine aortic endothelial cells (BAECs) and more NO generation from eNOS compared to control. Inhibition of Hsp90 by geldanamycin decreased eNOS activity and decreased endothelial viability. In conclusion, by changing eNOS structure, Hsp90 profoundly affected eNOS functions, including change of affinity of eNOS to cofactors like Ca2+, L-arginine, BH4 and further affecting NO generation capability. These specific cofactors regulated by Hsp 90 could become potential therapeutic targets of the eNOS-related diseases in future.

Cellular junctions play a critical role in structural connection and signal communication between cells in various tissues. Although there are structural and functional varieties, cellular junctions include tight junctions, adherens junctions, focal adhesion junctions, and tissue specific junctions such as PECAM-1 junctions in endothelial cells (EC), desmosomes in epithelial cells, and hemidesmosomes in EC. Cellular junction dysfunction and deterioration are indicative of clinical diseases. MicroRNAs (miRNA) are ~20 nucleotide, noncoding RNAs that play an important role in posttranscriptional regulation for almost all genes. Unsurprisingly, miRNAs regulate junction protein gene expression and control junction structure integrity. In contrast, abnormal miRNA regulation of junction protein gene expression results in abnormal junction structure, causing related diseases. The major components of tight junctions include zonula occluden-1 (ZO-1), claudin-1, claudin-5, and occludin. The miRNA regulation of ZO-1 has been intensively investigated. ZO-1 and other tight junction proteins such as claudin-5 and occludin were positively regulated by miR-126, miR-107, and miR21 in different models. In contrast, ZO-1, claudin-5, and occludin were negatively regulated by miR-181a, miR-98, and miR150. Abnormal tight junction miRNA regulation accompanies cerebral middle artery ischemia, brain trauma, glioma metastasis, and so forth. The major components of adherens junctions include VE-cadherin, β-catenin, plakoglobin, P120, and vinculin. VE-cadherin and β-catenin were regulated by miR-9, miR-99b, miR-181a, and so forth. These regulations directly affect VE-cadherin-β-catenin complex stability and further affect embryo and tumor angiogenesis, vascular development, and so forth. miR-155 and miR-126 have been shown to regulate PECAM-1 and affect neutrophil rolling and EC junction integrity. In focal adhesion junctions, the major components are integrin β4, paxillin, and focal adhesion kinase (FAK). Integrin β4 has been regulated by miR-184, miR-205, and miR-9. Paxillin has been regulated by miR-137, miR-145, and miR-218 in different models. FAK has been regulated by miR-7, miR-138, and miR-135. Deregulation of miRNAs is caused by viral infections, tumorigenesis, and so forth. By regulation of posttranscription, miRNAs manipulate junction protein expression in all cellular processes and further determine cellular fate and development. Elucidation of these regulatory mechanisms will become a new alternative therapy for many diseases, such as cancers and inflammatory diseases.

Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. In addition to producing NO, eNOS can also generate superoxide (O2-.) in the absence of the cofactor tetrahydrobiopterin (BH4). Previous studies have shown that bovine eNOS serine 1179 (Serine 1177/human) phosphorylation critically modulates NO synthesis. However, the effect of serine 1179 phosphorylation on eNOS superoxide generation is unknown. Here, we used the phosphomimetic form of eNOS (S1179D) to determine the effect of S1179 phosphorylation on superoxide generating activity, and its sensitivity to regulation by BH4, Ca2+, and calmodulin (CAM). S1179D eNOS exhibited significantly increased superoxide generating activity and NADPH consumption compared to wild-type eNOS (WT eNOS). The superoxide generating activities of S1179D eNOS and WT eNOS did not differ significantly in their sensitivity to regulation by either Ca2+ or CaM. The sensitivity of the superoxide generating activity of S1179D eNOS to inhibition by BH4 was significantly reduced compared to WT eNOS. In eNOS-overexpressing 293 cells, BH4 depletion with 10mM DAHP for 48 hours followed by 50ng/ml VEGF for 30 min to phosphorylate eNOS S1179 increased ROS accumulation compared to DAHP-only treated cells. Meanwhile, MTT assay indicated that overexpression of eNOS in HEK293 cells decreased cellular viability compared to control cells at BH4 depletion condition (P

To compare cardiopulmonary resuscitation (CPR) quality between manual CPR and miniaturized chest compressor (MCC) CPR. To improve CPR quality through evaluating the quality of our clinical work of resuscitation by real-time video recording system.The study was a retrospective observational study of adult patients who experienced CPR at the emergency department of Shanghai Tenth People's Hospital from March 2013 to August 2014. All the performance of CPR were checked back by the record of "digital real-time video recording system". Average chest compression rate, actual chest compression rate, the percentage of hands-off period, time lag from patient arrival to chest compression, time lag from patient arrival to manual ventilation, time lag from patient arrival to first IV establish were compared. Causes of chest compression hands-off time were also studied.112 cases of resuscitation attempts were obtained. Average chest compression rate was over 100 compression per minute (cpm) in the majority of cases. However, indicators such as percentage of hands-off periods, time lag from patient arrival to the first manual ventilation and time lag from patient arrival to the first IV establish seemed to be worse in the manual CPR group compared to MCC CPR group. The saving of operators change time seemed to counteract the time spent on MCC equipment. Indicators such as percentage of hands-off periods, time lag between patient arrival to the first chest compression, time lag between patient arrival to the first manual ventilation and time lag from patient arrival to the first IV establish may influence the survival.Our CPR quality remained to be improved. MCC may have a potentially positive role in CPR.

In addition to superoxide (O2.-) generation from nitric oxide synthase (NOS) oxygenase domain, a new O2.- generation site has been identified in the reductase domain of inducible NOS (iNOS) and neuronal NOS (nNOS). Cysteine S-glutathionylation in eNOS reductase domain also induces O2.- generation from eNOS reductase domain. However, the characteristics and regulatory mechanism of the O2.- generation from NOS reductase domain remain unclear. We cloned and purified the wild type bovine eNOS (WT eNOS), a mutant of Serine 1179 replaced with aspartic acid eNOS (S1179D eNOS), which mimics the negative charge caused by phosphorylationand truncated eNOS reductase domain (eNOS RD). Both WT eNOS and S1179D eNOS generated significant amount of O2.- in the absence of BH4 and L-arginine. The capacity of O2.- generation from S1179D eNOS was significantly higher than that of WT eNOS (1.74:1). O2.- generation from both WT eNOS and S1179D eNOS were not completely inhibited by 100nM tetrahydrobiopterin(BH4). This BH4 un-inhibited O2.- generation from eNOS was blocked by 10mM flavoprotein inhibitor, diphenyleneiodonium (DPI). Purified eNOS reductase domain protein confirmed that this BH4 un-inhibited O2.- generation originates at the FMN or FAD/NADPH binding site of eNOS reductase domain. DEPMPO-OOH adduct EPR signals and NADPH consumptions analyses showed that O2.- generation from eNOS reductase domain was regulated by Serine 1179 phosphorylation and DPI, but not by L-arginine, BH4 or calmodulin (CaM). In addition to the heme center of eNOS oxygenase domain, we confirmed another O2.- generation site in the eNOS reductase domain and characterized its regulatory properties.