Objective To investigate the impact of intraoperative red blood cell (RBC) transfusion volume on the postoperative oxygenation index in lung transplant recipients. Methods This retrospective study analyzed the clinical data of patients who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from 2021 to 2023. Patients were divided into a non-severe primary graft dysfunction (PGD) group and a severe PGD group based on whether their postoperative oxygenation index was>200 mm Hg at 0, 24, and 48 h. General patient data and intraoperative RBC transfusion volumes were compared between the two groups. A binary logistic regression model was constructed to explore the effect size (OR and its 95%CI) of RBC transfusion volume on postoperative oxygenation status at different time points (0, 24, and 48 h). The area under the receiver operating characteristic curve was calculated to evaluate the model's diagnostic performance. Results A total of 351 patients were included (260 males, 91 females), with ages ranging from 20 to 77 years. The OR for the effect of intraoperative RBC transfusion on poor oxygenation was 1.486 (95%CI 0.982 to 2.248, P=0.061) at 0 h postoperatively, 3.111 (95%CI 1.793 to 5.399, P<0.001) at 24 h, and 1.583 (95%CI 1.026 to 2.442, P=0.038) at 48 h. This indicated that as time progressed, the postoperative oxygenation status of lung transplant recipients was affected by the intraoperative transfusion volume. Furthermore, an RBC transfusion volume>975 mLhad a significant impact on patient oxygenation at 24 and 48 h postoperatively. Conclusion The volume of intraoperative RBC transfusion has a significant impact on the oxygenation status at 24 and 48 h postoperatively. Intraoperative RBC transfusion volume is associated with the occurrence of severe PGD after lung transplantation. Controlling the volume of RBC transfusion during lung transplantation may help reduce the incidence of severe PGD.

Background:Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials.Microbial agents,as environmentally friendly and efficient plant growth promoters and soil conditioners,have increasingly attracted attention in eco-agriculture research.Objective:Our understanding remains limited regarding how the application of microbial agents,alone or in combination,affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials.Methods:In this study,Epimedium pubescens Maxim.was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis)applied individually and in combination on plant growth and the accumulation of bioactive components.Additionally,this study explored the relationship between the rhizosphere microbiome and plant development.Results:The application of microbial agents increased the yield of E.pubescens leaves by 20.30％to 33.66％and enhanced the total flavonol glycosides content by 11.40％to 29.94％.Meanwhile,microbial treatments reshaped the rhizosphere microbiome,promoted the enrichment of beneficial microorganisms(e.g.,Frankia and Paenibacillus),suppressed phytopathogenic fungi such as Didymella and Scytalidium,and enhanced the stability of the soil microbial co-occurrence network.The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumula-tion of bioactive components by modulating the soil microbiome.Conclusion:These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere micro-biomes as mediated by microbial agents.They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.

Objective To investigate the different biomechanical effects of two types of palatal expanders and expansion sites on a bi-lateral complete cleft lip and palate(BCCLP)in mixed dentition with a finite element analysis(FEA).Methods The CBCT data of a patient with BCCLP were collected to construct a FEA model containing craniomaxillary suture structure.The fan-shaped and traditional Hyrax expanders were drawn and assembled into the FEA model in SolidWorks software according to the working conditions as follows:condition 1 and 2,the fan-shaped expander was placed at the anterior/posterior part of the palate respectively;condition 3 and 4,the Hyrax expander was placed at the anterior/posterior part of the palate respectively.A 5 N force in X axis direction was loaded at the apex of the expander coil spring.The stress distribution and initial displacement of craniomaxillary complex in four working conditions were compared.Results ①In working condition 1,2 and 3,the displacement of anterior part was larger than the posterior part of the dental arch.Under condition 4,the displacement of anterior,middle and posterior parts of dental arch were basically the same.②The maximum stress and displacement were observed at crowns in all working conditions.③There was a certain skeletal enlargement effect,which showed a gradually decreasing deformation trend from alveolar region to the upward region.Conclusion The expansion effect of fan-shaped expander is more suitable for BCCLP patients with extremely narrow anterior arch and normal posterior arch.For the tradi-tional Hyrax expander,the position has a great influence on expansion effect.It is showed that the dental support expander could pro-duce skeletal dilation effect in BCCLP patients during mixed dentition.

Background:Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials.Microbial agents,as environmentally friendly and efficient plant growth promoters and soil conditioners,have increasingly attracted attention in eco-agriculture research.Objective:Our understanding remains limited regarding how the application of microbial agents,alone or in combination,affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials.Methods:In this study,Epimedium pubescens Maxim.was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis)applied individually and in combination on plant growth and the accumulation of bioactive components.Additionally,this study explored the relationship between the rhizosphere microbiome and plant development.Results:The application of microbial agents increased the yield of E.pubescens leaves by 20.30％to 33.66％and enhanced the total flavonol glycosides content by 11.40％to 29.94％.Meanwhile,microbial treatments reshaped the rhizosphere microbiome,promoted the enrichment of beneficial microorganisms(e.g.,Frankia and Paenibacillus),suppressed phytopathogenic fungi such as Didymella and Scytalidium,and enhanced the stability of the soil microbial co-occurrence network.The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumula-tion of bioactive components by modulating the soil microbiome.Conclusion:These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere micro-biomes as mediated by microbial agents.They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.

Objective:Hepatocellular carcinoma(HCC)is the most common primary malignant tumor of the liver.The diagnosis rate of early HCC is low,and most patients are diagnosed at the late stage and have a very poor prognosis.Therefore,it is urgent to explore effective early diagnosis markers and intervention targets for HCC.Cancer/testicular antigen 1A(CTAG1A)is abnormally expressed and highly immunogenic in a variety of tumors,but its expression characteristics and immunogenicity in HCC remain unclear.The aim of this study is to identify the expression and immunogenicity of CTAG1A in HCC tissues and cells,providing a new biomarker for the early diagnosis of HCC and a new potential target for clinical immunotherapy.Methods:This study screened the differentially expressed gene profiles between 10 pairs of very early HCC(BCLC stage 0 HCC)tumors and paracancerous tissues using a transcriptome microarray.The expression of CTAG1A was verified by RT-qPCR in an independent large sample(BCLC stage 0,A,B,C HCC tissues and adjacent non-tumor tissues,n=149)and various hepatocellular carcinoma cell lines.Bioinformatics tools(TepiTool of IEDB database and Swiss Model)were used to predict the MHC-Ⅰ and MHC-Ⅱ epitopes of CTAG1A.The candidate peptides were synthesized by solid-phase polypeptide synthesis method.After purification by HPLC and verification by mass spectrometry assay,the specific T cell responses of peripheral blood mononuclear cells(PBMC)of 9 HCC patients to all peptides were detected by IFN-γ enzyme-linked immunospot assay(ELISpot).The clinical samples were collected from HCC patients admitted to the Third Affiliated Hospital of Naval Medical University(Eastern Hepatobiliary Surgery Hospital)from 2015 to 2022.The collection and usage of all samples were carried out with the consent of the patients,and with the approval of the Ethics Committee of Eastern Hepatobiliary Surgery Hospital(EHBHKY2015-01-017)and in strict accordance with relevant requirements and ethical regulations.Statistical analysis was performed using SPSS 30.0 software,and the diagnostic efficiency was evaluated by ROC curve.Results:Transcriptome chip screening results showed that CTAG1A expression was significantly up-regulated in the very early-stage HCC(BCLC stage 0 HCC)(|FC|=99.16,P<0.0001).The verification using the clinical independent samples showed its high expression in all stages of HCC and better diagnostic efficacy in early-stage HCC(BCLC stage 0 HCC AUC=0.6893,sensitivity=85.71%;BCLC stage A HCC AUC=0.8229,sensitivity=83.33%).Furthermore,the expression of CTAG1A was significantly higher in multiple liver cancer cell lines than in relatively normal liver cell lines(P<0.001).Compared with alpha-fetoprotein(AFP),CTAG1A showed better diagnostic efficacy in BCLC stage 0 and stage A HCC(ROC curve analysis of AFP showed no significant difference in early HCC,P>0.05).Bioinformatics tools predicted that CTAG1A contained 8 MHC-type I and 4 MHC-type II epitopes.The IFN-γ ELISpot assay showed that 12 synthetic peptides could induce PBMC specific T cell response in HCC patients to varying degrees.Conclusion:CTAG1A is significantly overexpressed in early-stage HCC and has multi-epitope immunogenicity,which may activate CD8? and CD4? T cells,suggesting its potential as a target for HCC immunotherapy.It may provide a new direction for developing combined immunotherapy strategies based on mRNA vaccines or adoptive cell therapy.Compared with AFP,CTAG1A exhibits better diagnostic efficacy in early-stage HCC,suggesting its potential as a marker for early diagnosis of HCC.

Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

Objective:To identify the key differentially expressed gene, BTF3, in cutaneous squamous cell carcinoma(cSCC)using bioinformatics methods and to preliminarily explore the potential mechanisms of BTF3 and its co-expressed genes in cSCC development. Methods:The cSCC-related datasets(GSE98767, GSE42677, GSE45164)were obtained from the Gene Expression Omnibus(GEO)database.Differential expression analysis revealed BTF3 as a significantly differentially expressed gene in cSCC.A BTF3-related co-expressed gene network was constructed and subjected to gene ontology(GO)enrichment analysis to investigate the biological processes, molecular functions, and cellular components that were significantly enriched.The study selected 60 paraffin-embedded tissue samples from the First Affiliated Hospital of Jinzhou Medical University, collected between 2020 and 2024.This cohort included 30 samples from cSCC patients and 30 samples from patients who underwent excision of melanocytic nevi.Immunohistochemical experiments were conducted to assess the expression of BTF3 in cSCC tissues.Additionally, single-sample gene set enrichment analysis(ssGSEA)was performed to assess the relevance of BTF3 to immune cells, and protein-protein interaction(PPI)analysis was employed to identify critical gene networks. Results:BTF3 was significantly overexpressed in cSCC, as confirmed by immunohistochemistry.The receiver operating characteristic(ROC)curve indicated that BTF3 exhibited moderate classification accuracy.Co-expression analysis revealed that positively correlated genes with BTF3 included EIF3E and HSPA14, while negatively correlated genes included SZRD1 and ARHGEF2.GO analysis demonstrated that BTF3 was enriched in biological processes such as glucose metabolism, signaling in response to deoxyribonucleic acid (DNA)damage, endogenous apoptotic signaling pathways, platelet morphogenesis, and platelet formation.Additionally, ssGSEA indicated a significant association of BTF3 with memory B cells and a notable correlation with low CD56-expressing natural killer cells. Conclusions:BTF3 is significantly overexpressed in cSCC and may represent a promising diagnostic and therapeutic target by influencing key gene networks and modulating the immune microenvironment.

Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.

Objective:To explore the construction requirements and solutions for a digital full-process management platform for Investigator-Initiated Trials (IIT) in pediatrics in China.Methods:By reviewing literature, the current status and highlights of pediatric IIT digital management systems in Europe and the United States were analyzed. The challenges faced in building a digital full-process management platform for pediatric IIT in China were summarized. The exploration and implementation achievements of our hospital in platform construction were introduced, and future construction priorities were proposed based on practical considerations.Results:The construction and application of digital full-process management platforms for pediatric IIT in Europe and the United States were relatively mature, providing comprehensive digital support for pediatric IIT research, ranging from project management to research design implementation, multi-center data interoperability, and personnel training. In China, the pediatric IIT digital management platform was still under construction, with main challenges including the formulation of construction plans based on hospital-specific conditions, data standardization, and remote recruitment and follow-up platforms.Conclusions:Considering the current status of pediatric IIT digital full-process management systems both domestically and internationally, efforts should be made to further strengthen data standardization, remote subject management, and digital pediatric IIT training from both policy and technical perspectives. This will provide one-stop services and management for projects and researchers, promoting the development of pediatric medical research.

Objective:To explore the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) technology in pediatric urinary tract infections (UTI).Methods:In this retrospective study, the clinical data of children with UTI admitted to the Department of Nephrology, Children′s Hospital, Capital Institute of Pediatrics, from March 2023 to March 2024 were collected.The positive detection rates, timeliness, and consistency of mNGS technology were compared with those of urine culture.Measurement data were subject to test of normality.The independent sample t test, Chi-square test or Fisher′s exact probability test were used for comparison between groups. Results:A total of 193 patients were included.The positive detection rate of urine culture was 36.3% (70/193).Among 42 patients who underwent mNGS testing, 37 cases (88.1%) tested positive.The positive detection rate of mNGS was significantly higher than that of urine culture ( χ2=37.357, P<0.001).It took significantly less time to report mNGS results than to report urine culture results ( Z=3.524, P<0.001).In the 42 cases that underwent mNGS testing, 5 cases (11.9%) were negative for urine pathogens by both methods, and 21 cases (50.0%) were positive by mNGS but negative by urine culture.Among the remaining 16 cases (38.1%) positive by both mNGS and urine culture, 14 cases (33.3%) achieved fully matching results, 1 case (2.4%) was fully mismatched, and 1 case (2.4%) was partially matched.Comparison of the positive detection rate and the duration of anti-infective treatment prior to specimen collection between urine culture and mNGS showed that the median durations for urine culture and mNGS positivity were 5 and 20 days, and the difference was statistically significant ( χ2=0.537, P<0.001). Conclusions:mNGS technology has high sensitivity for diagnosing pathogens in pediatric UTI.Compared with urine culture, mNGS provides good consistency and significantly shortens the detection time.The positive detection rate is less affected by antimicrobial treatment.For children with UTI, especially those who have failed empirical anti-infective treatment and whose pathogen cannot be identified by urine culture, mNGS testing is recommended as early as possible.