Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

Clinical research on rare diseases has always faced multiple challenges in clinical research design and implementation due to small sample sizes of patients,high heterogeneity,and limited research resources.The rapid development of digital intelligence technology has provided innovative solutions for rare disease research.This article systematically explores the current status and response strategies of clinical research on rare diseases in the digital intelligence age.On the one hand,the efficiency of rare disease research has been optimized through adaptive design,mixed trial mode,and precision medicine stratification methods.On the other hand,solutions based on digital technology have been proposed to address the practical challenges of recruitment difficulties and underrepresentation of rare disease clinical research patients,data management and technical barriers,and insufficient coverage of natural medical history and baseline databases through digital intelligence technology.By combining international collaboration,intelligent screening,and remote experiments,a multidisciplinary collaboration and international cooperation,adaptive design,digital data platform,and patient-centered remote research model have been constructed as the core implementation strategies.Typical cases demonstrate that digital intelligence technology not only effectively shortens the drug development cycle,but also significantly enhances patient benefits,providing a replicable practical paradigm for global rare disease research.The practice of digital platforms represented by the International Rare Disease Research Alliance and the China Rare Disease Diagnosis and Treatment Collaboration Network has further verified the feasibility and promotional value of the digitalization path.In summary,digital intelligence technology has shown considerable promise in overcoming the clinical research challenges of rare diseases and accelerating the development of treatment plans,providing systematic references for researchers,regulatory agencies,and patient organizations.It is expected to drive the clinical research of rare diseases towards a more efficient and accurate future.

Objective To investigate the factors associated with coronary microvascular dysfunction(CMD)after percutaneous coronary intervention(PCI)in diabetic patients with multivessel disease and non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods A single-center retrospective study was conducted,including 242 diabetic patients with NSTE-ACS and multivessel disease who underwent PCI between January 2021 and June 2024 at Hospital.Baseline characteristics,procedural parameters,and laboratory indicators were collected.CMD was defined based on immediate postoperative coronary functional measurements[computational pressure-flow dynamics derived angiography fractional flow reserve(caFFR)＞0.80 and coronary angiography-derived index of microcirculatory resistance(caIMR)≥25].Univariate and multivariate logistic regression analyses were performed to identify risk factors for CMD.Results Among the 242 patients,49(20.2%)were diagnosed with patient-level CMD after PCI.The CMD group showed significantly higher hemoglobin levels compared to the non-CMD group[136.00(130.00,150.00)g/L vs.130.00(119.00,145.00)g/L,P=0.012],as well as higher glutamic-pyruvic transaminase levels[20.00(16.00,31.00)U/L vs.18.00(13.00,26.00)U/L,P=0.047].However,there were no significant differences between the groups in terms of diabetes duration,traditional cardiovascular risk markers(hypertension,smoking history,low-density lipoprotein cholesterol),types of hypoalycemic agents,or procedural parameters(all P＞0.05).Univariate regression analysis indicated that hemoglobin(OR 1.025,95%CI 1.007-1.043,P=0.007)and urea(OR 0.897,95%CI 0.791-1.108,P=0.091)were associated with CMD.Multivariate logistic regression further confirmed that elevated hemoglobin concentration was an independent predictor of CMD after PCI in diabetic patients with NSTE-ACS and multivessel disease(OR 1.026,95%CI 1.007-1.045,P=0.006).According to the Youden index of the receiver operating characteristics curve,the optimal cutoff value for diagnosing hemoglobin content is 131 g/L(Youden Index=0.238,sensitivity 69.4%,specificity 54.4%).Conclusions Elevated hemoglobin concentration is an independent risk factor for CMD after PCI in diabetic patients with NSTE-ACS and multivessel disease,potentially linked to hyper-viscous blood-induced oxidative stress and endothelial injury.It is recommended to intensify postoperative microcirculatory monitoring in patients with preoperative hemoglobin≥131 g/L and to explore hemorheological intervention strategies.

Objective"Red butterfly sore","yin-yang toxin"and"Bi disease"are different Chinese medicine diagnoses of systemic lupus erythematosus(SLE).It is not clear whether there are biological differences between these three types of Chinese medicine diagnoses.The aim of this study was to compare the different TCM diagnoses of SLE patients from the perspective of lymphocyte subsets and cytokines.Methods Patients diagnosed with SLE in our hospital from June 1,2021 to December 1,2023 were retrospectively collected,and the differences of T cell subsets,NK cells,B lymphocytes and Th1,Th2 and Th17 cytokines among different groups were compared by one-way ANOVA or nonparametric test.As well as differences in laboratory test indicators such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),immunoglobulin,and complement,receiver operating characteristic curve(ROC curve)was used to analyze the value of these indexes in the differential diagnosis of different types of SLE.Results From June 1,2021 to December 1,2023,291 patients diagnosed with SLE in our hospital for the first time were collected,and 104 cases meeting the exclusion criteria of this study were included,including 31 cases of red butterfly sores,30 cases of yin-yang toxin and 43 cases of BI disease.The absolute number and percentage of CD8+T cells,interleukin-10(IL-10)content and tumor necrosis factor α(TNF-α)content were different among the three groups of SLE patients diagnosed by different Chinese medicine,and the absolute number of CD8+T cells in the red butterfly sore group was significantly higher than that in the yin-yang toxicities group(P=0.039)and the disease group(P=0.008).CD8+T cell percentage in red butterfly sore group was significantly higher than that in yin-yang toxin group(P=0.014)and disease group(P=0.004),IL-10 and TNF-α levels in red butterfly sore group were significantly lower than those in disease group(P=0.015,P=0.036),and ROC curve analysis showed that,the absolute number and percentage of CD8+T cells can effectively distinguish red butterfly sores from yin-yang toxins(AUC=0.65,AUC=0.61,P<0.05),and the absolute number and percentage of CD8+T cells,IL-10 and TNF-α can effectively distinguish red butterfly sores from diseases(AUC=0.68,AUC=0.66,P<0.01,AUC=0.67,AUC=0.64,P<0.05).Conclusion Immune lymphocyte subtypes,cytokines,especially the absolute number and percentage of CD8+T cells,IL-10 and TNF-α may play an important role in the identification of different TCM diagnosis of SLE.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Objective:To investigate the molecular mechanisms of bexarotene in treating double hit lymphoma(DHL)based on Weighted Gene Co-expression Network Analysis(WGCNA),thereby providing potential targets and experimental evidence for DHL treatment.Methods:The gene expression datasets GSE44164 and GSE43677 were downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)were identified.WGCNA was employed to identify gene modules associated with DHL.A protein-protein interaction(PPI)network was constructed to screen for key hub genes.Drug-gene association analysis was conducted using the EpiMed platform to identify potential targeted drugs for DHL.The effects of bexarotene on DHL cell proliferation and key protein expression were evaluated using the CCK-8 assay and Western blotting(WB),and its effects on cell apoptosis was evaluated using flow cytometry.Results:WGCNA identified a turquoise module highly associated with DHL,and 10 hub genes(COL1A2,COL3A1,MMP2,COL5A2,DCN,BGN,FN1,MMP9,FBN1,and LUM)were screened from the PPI network.Drug association analysis nominated bexarotene as a potential therapeutic agent.In vitro validation demonstrated that bexarotene significantly inhibited U2932 cell viability(P<0.05),promoted cell apoptosis(P<0.001),and downregulated c-Myc and COL1A2 expression(P<0.05).Conclusion:Bexarotene may exert anti-DHL effects by suppressing the c-Myc signaling pathway and modulating extracellular matrix-related genes.Further studies are warranted to validate its in vivo efficacy and potential for combination therapy.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.