Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

Objective:To explore the clinical characteristics of neonatal necrotizing enterocolitis（NEC）and analyze the risk factors for early-onset NEC.Methods:A total of 220 children with NEC admitted to the Department of Pediatrics，Tianjin Medical University General Hospital from January 1st，2018 to February 29th，2024 were retrospectively selected as the research objects. According to the time of onset，the early-onset group（ n=120）and the late-onset group（ n=100）were established，and the clinical characteristics of the two groups were compared. Another 150 cases of normal healthy newborns born in this hospital in the same period were selected as the control group，and the clinical data of the control group were collected. The clinical characteristics of the early-onset group and the control group were compared，and the risk factors of early-onset NEC were analyzed by multivariate Logistic regression. Results:Compared with the late-onset group，the early-onset group had fever［50.0%（60/120）vs. 40%（40/100）， χ2=7.333， P=0.007］，apnea［39.17%（47/120）vs. 28%（28/100）， χ2=7.568， P=0.006］，no rise in body temperature［56.67%（68/120）vs. 39%（39/100）， χ2=6.815， P=0.009］，abdominal distension［25%（30/120）vs. 40%（40/100）， χ2=13.200， P<0.001］，vomiting［30.83%（37/120）vs. 45%（45/100）， χ2=12.797， P<0.001］was significantly different（all P<0.05）；Multivariate Logistic regression analysis：weight<1 500 g（ OR=5.871，95% CI：3.153～9.673， P<0.001），gestational age<30 weeks（ OR=4.256，95% CI：2.641～7.896， P=0.007），hemodynamically significant patent ductus arteriosus（hs-PDA）（ OR=3.113，95% CI：1.865～5.133， P=0.033），severe anemia（ OR=3.057，95% CI：2.165～4.802， P=0.001），feeding intolerance（ OR=4.215，95% CI：1.579～10.802， P=0.005），amniotic fluid pollution（ OR=2.452，95% CI：1.579～3.111， P<0.001）were the independent risk factors for early-onset NEC（all P<0.05）. Conclusion:Weight<1 500 g，gestational age<30 weeks，hs-PDA，severe anemia，feeding intolerance，and amniotic fluid contamination are independent risk factors for early-onset NEC. In clinical practice，more attention should be paid to these factors for disease prevention，early identification，and timely intervention in newborns to reduce the occurrence of NEC.

Objective To investigate the relationship between serum melatonin and prostaglandin E2(PGE2)levels with disease severity and prognosis of necrotizing enterocolitis(NEC)in premature infants.Methods A total of 215 premature infants diagnosed with NEC(NEC group)admitted to our hospital between January 2022 and February 2025 and 80 healthy premature infants(control group)were prospectively enrolled.NEC cases were stratified by Bell's staging divided into mild(n=67),moderate(n=90),and severe(n=58)subgroups.Serum levels of melatonin and PGE2 were measured by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to assess the relationship between serum melatonin,PGE2 levels and Bell staging.According to the 28-day prognosis assessment,NEC infants were divided into a poor prognosis group and a good prognosis group.Multivariate logistic regression and ROC analysis were used to explore the association and predictive value of serum melatonin and PGE2 levels in NEC prognosis,and decision curve analysis(DCA)was used to evaluate clinical net benefit.Results Compared with the control group,the NEC group had significantly lower serum melatonin levels and higher PGE2 levels(P<0.05).Among the NEC subgroups,serum melatonin levels decreased and PGE2 levels increased progressively from mild to severe NEC(P<0.05).Serum melatonin was negatively correlated with Bell stage,while PGE2 was positively correlated(P<0.05).The 28-day poor prognosis rate in NEC infants was 18.60%(40/215).Severe disease and elevated PGE2 were independent risk factors for poor prognosis,while higher birth weight and increased melatonin were independent protective factors(P<0.05).The area under the ROC curve(AUC)for predicting prognosis using melatonin,PGE2,and their combination was 0.797,0.780,and 0.880,respectively,with the combined prediction performing significantly better than either biomarker alone(P<0.05).DCA indicated that when the threshold probability exceeded 0.1,the net benefit of the combined model was greater than that of either marker alone.Conclusion In premature infants with NEC,reduced serum melatonin and elevated PGE2 levels are associated with increased disease severity and poor prognosis.The combination of serum melatonin and PGE2 levels provides high predictive value for prognosis.

Objective:To investigate whether killer immunoglobulin-like receptor(KIR)genotypes and haplotype are associated with the dry eye disease(DED)in a Chinese Han population.Methods:Polymerase chain reaction with sequence-specific primers(PCR-SSP)method was used to genotype KIR genes in 106 DED patients and 220 healthy controls.Results:A total of 23 KIR geno-types were found in DED patients and healthy controls,including 10 newly discovered KIR genotypes.The genotype G and haplotype 4 were associated with respectively increased risk of DED(P=0.025,P=0.004);while the haplotype 2 appeared to have an inverse asso-ciation with the disease(P=0.016).The frequency of KIR genotype B/B in DED patients was also significantly higher than that in con-trol group(P=0.027).KIR haplotype A and B had distinctive centromeric(Cen)and telomeric(Tel)gene-content motifs,and the Cen-B/B was associated with increased risk of DED(P=0.037).Conclusion:There may be an association between KIR genotype and hap-loid type with DED in Han population.

Objective: To investigate the expression of peroxiredoxin 4 (PRDX4) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration, and invasion of OSCC cells. Methods: The Cancer Genome Atlas(TCGA) database was used to analyze the expression of PRDX4 in OSCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot (WB) were used to detect the mRNA and protein expression of PRDX4 in OSCC cell lines and normal oral mucosal epithelial cells. PRDX4 was knocked down in CAL-27 cells and divided into two groups: the si-PRDX4 group and si-NC group. SCC-9 cells overexpressing PRDX4 were divided into two groups: the PRDX4 overexpression group (transfected with pcDNA3.1-PRDX4 plasmid) and the vector group (the control group; transfected with pcDNA3.1-NC plasmid). A cell counting kit-8 (CCK-8) and plate colony formation assay were used to detect cell proliferation. Transwell assay and cell scratch test were used to detect cell invasion and migration ability. WB was used to detect the effects of knockdown or overexpression of PRDX4, p38MAPK agonist or inhibitor on the expression of p38MAPK-related signaling pathway proteins, and epithelial mesenchymal transition proteins in OSCC cells. Results: PRDX4 was highly expressed in OSCC tissues and cell lines. The results of qRT-PCR and WB showed that PRDX4 was highly expressed in OSCC cell lines compared with normal oral mucosal epithelial cells. The CCK-8 assay showed that the si-PRDX4 group had significantly lower OD values than the si-NC group at 24, 48, and 72 h (P<0.05). The PRDX4 overexpression group had a significantly higher OD value than the vector group at 24, 48, and 72 h (P<0.05). The plate colony formation assay showed that the si-PRDX4 group had a significantly lower number of colonies than the si-NC group (P<0.05). The number of colonies formed in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The cell scratch test showed that the wound healing area of the si-PRDX4 group was less than that of the si-NC group (P<0.05). The scratch healing area of the PRDX4 overexpression group was significantly higher than that of the vector group (P<0.05). The Transwell invasion assay showed that the number of transmembrane cells in the si-PRDX4 group was lower than that in the si-NC group (P<0.05). The number of transmembrane cells in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The WB results showed that knockdown and overexpression of PRDX4 could downregulate and upregulate the expression of the p38MAPK signaling pathway and epithelial-mesenchymal transition related proteins, respectively, and the addition of p38MAPK agonist and inhibitor could significantly reverse the expression of related proteins. Conclusion PRDX4 is highly expressed in OSCC. Knocking down the expression of PRDX4 in OSCC cells can downregulate the expression of p38 MAPK signal axis and EMT-related signal proteins, thereby inhibiting the proliferation, migration, invasion, and epithelial-mesenchymal transition of cells.

Objective:To evaluate the relationship between intraoperative hypothermia and early postoperative pulmonary complications (PPCs) in pediatric patients undergoing living donor liver transplantation (LDLT).Methods:This was a retrospective study. Medical records of pediatric patients of either sex, aged 4-24 months, diagnosed with congenital biliary atresia who underwent LDLT from January 2021 to March 2023 were collected from the electronic medical record system of Tianjin First Central Hospital. The collected data included general characteristics, intraoperative conditions, and PPCs such as postoperative pediatric acute respiratory distress syndrome, pneumonia, pleural effusion, atelectasis, and pulmonary edema within 1 week after operation. Additional indicators comprised the difference in systemic immune-inflammation index (SII) between 1 day before surgery and at the end of surgery (ΔSII), concentration of hypersensitive C-reactive protein (hs-CRP) at the end of surgery, postoperative mechanical ventilation time, and duration of intensive care unit stay. Pediatric patients were divided into PPCs group and non-PPCs group based on the development of PPCs. Logistic regression analysis was used to determine the relationship between factors associated with intraoperative hypothermia and PPCs.Results:A total of 226 pediatric patients were included in the study, with 126 cases in PPCs group and 100 cases in non-PPCs group. The results of logistic regression analysis showed that pre-reperfusion hypothermia, duration of hypothermia, ΔSII and concentrations of hs-CRP at the end of operation were independent risk factors for the occurrence of PPCs ( P<0.05). The area under the receiver operating characteristic curve of pre-reperfusion hypothermia and duration of hypothermia in predicting PPCs was 0.594 (95% confidence interval [ CI] 0.521-0.668, P=0.015) and 0.702 (95% CI 0.634-0.770, P<0.001), respectively. The area under the receiver operating characteristic curve of combination of factors associated with hypothermia (pre-reperfusion hypothermia, duration of hypothermia) and inflammatory indicators (ΔSII, plasma hs-CRP concentration at the end of surgery) in predicting PPCs was 0.977 (95% CI 0.959-0.995, P<0.001). Conclusions:Pre-reperfusion hypothermia and duration of hypothermia are independent risk factors for early PPCs in infants, and their predictive value for the development of PPCs is higher when combined with ΔSII and plasma hs-CRP concentration in pediatric patients undergoing LDLT.

Objective:To explore the psychological experience of ICU nurses caring for young patients with suicide attempts in a general hospital, and to lay a foundation for the study of psychological adjustment and intervention for ICU nurses.Methods:Twelve ICU nurses who had experience of caring for suicide attempted- young patients from Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University were selected by using descriptive qualitative research method and the maximum difference method of the purposive sampling during October to December in 2023, and semi-structured in-depth personal interviews were conducted. Traditional content analysis method was used to sort out and analyze the data and extract the themes.Results:A total of 12 nurses completed the interview, 5 males, 7 females, aged 23-38(29.33 ± 4.14) years, three themes and seven sub-themes were extracted: psychological characteristics of care (avoidance of active communication, fear of care, empathy); the support required for nursing care (support from colleagues; support from nursing managers); self-growth after caregiving (self-growth in terms of life and death, and self-growth in terms of children′s education).Conclusions:ICU nurses have a certain degree of psychological pressure when taking care of young patients with suicide attempts, which will produce empathy for patients and affect their self-values. At the same time, they need support from colleagues and nursing managers. Therefore, general hospitals should pay attention to the psychological state of ICU nurses, carry out the targeted communication training and mental health support for ICU nurses, and help them gain positive nursing career growth and values.

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Objective:To investigate whether killer immunoglobulin-like receptor(KIR)genotypes and haplotype are associated with the dry eye disease(DED)in a Chinese Han population.Methods:Polymerase chain reaction with sequence-specific primers(PCR-SSP)method was used to genotype KIR genes in 106 DED patients and 220 healthy controls.Results:A total of 23 KIR geno-types were found in DED patients and healthy controls,including 10 newly discovered KIR genotypes.The genotype G and haplotype 4 were associated with respectively increased risk of DED(P=0.025,P=0.004);while the haplotype 2 appeared to have an inverse asso-ciation with the disease(P=0.016).The frequency of KIR genotype B/B in DED patients was also significantly higher than that in con-trol group(P=0.027).KIR haplotype A and B had distinctive centromeric(Cen)and telomeric(Tel)gene-content motifs,and the Cen-B/B was associated with increased risk of DED(P=0.037).Conclusion:There may be an association between KIR genotype and hap-loid type with DED in Han population.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.