T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.

AIM: To explore the efficacy of internal limiting membrane(ILM)flap technique and simple ILM peeling in the treatment of idiopathic macular hole(IMH)and related influencing factors.METHODS: A retrospective cohort study was conducted on totally 32 patients(35 eyes)with IMH who received surgery at our department from January 2023 to November 2024. All the patients simultaneously received phacoemulsification combined with intraocular lens implantation, and they were divided into study group(19 eyes)and control group(16 eyes), with ILM flap technique and simple ILM peeling received in the two groups, respectively. The closure situation of macular hole, best corrected vision acuity(BCVA), and macular structure were observed in the two groups of patients. Furthermore, the correlation of BCVA and healing type of macular hole at the last time of follow-up with each parameter was analyzed.RESULTS: There was no statistical difference between the two groups of patients in preoperative general characteristics(all P>0.05). At the last time of follow-up, the macular hole was heeled in both groups, with 7 eyes of U-shaped heeling, 6 eyes of V-shaped heeling, and 6 eyes of irregular heeling in the study group, and with 13 eyes of U-shaped of heeling, 1 eye of V-shaped heeling and 2 eyes of irregular heeling in the control group(χ2=7.167, P=0.028). The postoperative BCVA was better than preoperative level(all P<0.05), there were no statistical significant differences between the two groups of patients in macular choroidal thickness before and after surgery(P>0.05), but the macular retinal thickness of the study group was thinner than that of the control group(168.11±92.11 vs 235.56±92.18 μm, P=0.03). Pearson correlation analysis indicated that BCVA at the last time of follow-up was positively correlated with the preoperative minimum diameter(r=0.476, P<0.05)and the diameter hole index(r=0.361, P<0.05), and negatively correlated with traction hole index(r=-0.364, P=0.031); Keendall correlation analysis showed that the postoperative closure types positively correlated with the basal diameter(τ=0.296, P=0.029), minimum diameter(τ=0.366, P=0.007), and visual acuity at the last time of follow-up(τ=0.412, P=0.003), while negatively correlated with macular hole index(τ=-0.415, P=0.002)and traction hole index(τ=-0.511, P<0.01). During the follow-up period, neither group of patients experienced postoperative complications.CONCLUSION: Both ILM flap technique and simple ILM peeling are safe and effective in treating IMH. As the smaller the basal diameter and minimum diameter of the macular hole, the larger the macular hole index and traction hole index, the probability of U-shaped heeling after surgery is greater and the visual acuity is better.

Objective:To investigate the mutations of TP53 and KRAS genes in the patients with six common types of digestive system tumors,including colorectal cancer(COAD),cholangiocarcinoma(CHOL),gallbladder cancer(GBC),liver hepatocellular carcinoma(LIHC),stomach adenocarcinoma(STAD),and pancreatic adenocarcinoma(PAAD),and to analyze the relationships between TP53 and KRAS gene mutations and clinical pathological characteristics,tumor mutation burden(TMB),and microsatellite instability(MSI)of the patients.Methods:The pathological paraffin or biopsy samples of 112 patients from January 2022 to December 2023 diagnosed with six types of tumors based on imaging and pathology were collected.Hybrid capture-based gene sequencing technology was used to detect TP53 and KRAS gene mutations in the patients with different types of tumors;mutation landscapes of common digestive system tumor samples were constructed.The patients were divided into high and low TMB groups according to the TMB levels.The mutation statuses of TP53 and KRAS genes in the patients with different types of digestive system tumors were compared,and the TP53 and KRAS gene mutations in the patients with different clinicopathological characteristics were examined.Results:A total of 276 mutations were detected in the 112 samples,with the highest mutation rate in TP53 gene(67％),followed by KARS gene(34％).TP53 gene mutation was most prominent in COAD,followed by LIHC,while KRAS gene mutation was most significant in PAAD.TP53 gene mutation mainly occurred in exons 5-8,while the KRAS gene mutation primarily occurred in exon 2.There was no statistically significant difference in TP53 gene mutation rate among the six types of digestive system tumors(P＞0.05),while the KRAS gene mutation rate showed statistically significant difference(P＜0.05).The mutation rates of TP53 and KRAS gene co-mutation also showed statistically significant difference among the six types of tumors(P＜0.05).There were statistically significant differences in TP53 and KRAS gene mutation rates between the patients with high TMB and low TMB(P＜0.05),while there were no statistically significant differences in TP53 and KRAS mutation rates between the patients with different sex,age,tumor size,differentiation degree,TNM stage,lymph node and/or distant metastasis and MSI(P＞0.05).Conclusion:The mutation rates of TP53 and KRAS genes are higher in common digestive system tumors,which are related to tumor types and TMB.

OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objective To retrieve and evaluate the evidence related to surgical instrument management,and to integrate the evidence to provide an evidence-based basis for clinical surgical instrument management practice.Methods Evidence on surgical instrument management,including guidelines,expert consensuses,and clinical decision-making,was systematically searched from domestic and international databases and related websites.The search timeframe was from database construction to 4 November 2024.Literature was screened and evaluated,and the evidence was integrated by 2 researchers.Results A total of 16 papers were included,including 2 systematic evaluations,1 class experimental study,2 clinical decisions,4 expert consensuses,5 guidelines,and 2 evidence summaries,resulting in a total of 33 pieces of evidence in 5 areas,including requirements for surgical instrument management,general principles of surgical instrument handling,logistics and supply chain management of surgical instruments,surgical instrument pre-treatment and cleaning,disinfection,and sterilisation processes,and personnel training.Conclusion This study summarises the best available evidence on the management of surgical instruments in hospitals and provides an evidence-based basis for healthcare professionals to manage surgical instruments,thereby improving the quality and efficiency of surgical instrument disposal.

Objective:To investigate the follow-up colonoscopy of patients after colorectal adenoma (CRA) resection, so as to improve colonoscopy quality and reduce missed CRA diagnosis.Methods:A total of 189 patients after CRA resection who underwent follow-up colonoscopy from October 2020 to October 2021 were consecutively recruited. The effect of bowel preparation was evaluated by the Boston bowel preparation scale (BBPS). The location, the number, and gross morphology of adenomas during CRA resection and two colonoscopies during 1 year follow-up after the resection were recorded, and their correlation with major clinicopathologic features were analyzed, and the missed CRA in follow-up colonoscopy were also analyzed.Results:The BBPS scores of the right colon, transverse colon, left colon and total colon in 189 patients who underwent CRA resection were 1.93±0.42, 2.53±0.52, 2.77±0.45, and 7.22±1.03 points at the 1-year follow-up colonoscopy and 2.08±0.35, 2.70±0.46, 2.81±0.40, and 7.57±0.84 points at the time of CRA resection. Except for the left colon segment ( χ 2=0.98, P>0.05), the differences in other colon segments were significantly different ( P<0.05). At the time of CRA resection, 62, 66, 210 and 338 CRAs were detected in the right colon, transverse colon, left colon and total colon segments, respectively. At the 1-year follow-up colonoscopy, 21, 38, 49 and 108 CRAs were missed in the corresponding colon segments and total colon, respectively. CRA missed diagnosis was related to patient age (≥60 years accounting for 54.2%), gender (males accounting for 81.9%), adenoma location (predominantly in the left colon comprising 36.2%) and gross morphology (flat types representing 72.3%) ( P<0.05), but not related to being vegetarian, history of cholecystectomy or appendectomy, smoking or alcohol consumption, number of adenomas or pathological type ( P>0.05). Conclusion:The missed diagnosis of CRA in patients after CRA resection primarily involves the flat type adenomas, which is associated with the age, gender, adenoma location within the colon and the gross morphology.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.