Based on plasma lipidomics combined with machine learning approaches, this study aimed to screen molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients and to evaluate their diagnostic performance.

Objective: To retrospectively assess whether a lower hematocrit level (between 18% and 20%) had any impact on the safety of patients undergoing therapeutic plasma exchange (TPE), and to further determine the threshold for red blood cell supplementation prior to TPE. Methods: Clinical data from 181 adult patients who underwent TPE treatment at the Department of Blood Transfusion of our hospital from March 2023 to July 2024 were collected. The patients were divided into a study group of 44 patients (Hct ≥18% and <20%) and a control group of 137 patients (Hct≥20%). In two groups, blood volume-related safety indicators including respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation levels before and after TPE were compared using t-test. Between-group differences in the grading of adverse reactions such as allergies and hypotension were analyzed using chi-square test. Results: A total of 659 TPE treatments were performed on 181 patients, with 169 TPE treatments on 44 patients in the study group (Hct≥18% and <20%) and 490 TPE treatments on 137 patients in the control group (Hct≥20%). There were no statistically significant differences in age, gender, BMI category, and the presence of cardiac insufficiency between the two groups. In the study group, there were no statistically significant differences in safety indicators such as respiration rate, heart rate, systolic blood pressure, and blood oxygen saturation level before and after TPE. In the control group, there were no statistically significant differences in heart rate and systolic blood pressure before and after TPE, but there were statistically significant differences in respiration rate and blood oxygen saturation level (P<0.05). There were no statistically significant differences in the grading of adverse reactions such as allergic reactions and hypotension between the two groups. Conclusion: For adult patients with stable conditions, maintaining a lower hematocrit level (Hct ≥18% and <20%) during TPE is relatively safe. It is feasible to lower the TPE red blood cell supplementation threshold to 18%≤Hct<20%，which may save blood resources while potentially benefit patients by avoiding unnecessary red blood cell transfusion.

Objective: To investigate the clinical symptoms, laboratory tests, and treatment strategies of a case of fetal/neonatal alloimmune thrombocytopenia (FNAIT) complicated with piperacillin drug antibody. Methods: The platelet antibodies in the mother were screened and identified by ELISA. The HLA antigens of the newborn were genotyped through PCR-SSO, while the specificity of HLA antibodies in the mother was determined using a Single Antigen kit. The drug antibody was detected by a piperacillin kit. Results: Maternal antibodies against paternally-derived platelet antigens were detected. The HLA genotypes of the newborn were identified as HLA A 33∶03 and HLA B 58∶01. The mother exhibited strong positive antibodies against the specific platelet antigens of the newborn, namely anti-HLA-A33 and anti-HLA-B58 antibodies. The piperacillin antibody was detected in the newborn. Following treatment of continuous intravenous immunoglobulin (IVIG), platelet transfusions, red blood cell transfusions and discontinuation of piperacillin treatment, the platelet count and hemoglobin levels increased in the newborn. Conclusion: The newborn in this case was diagnosed with FNAIT complicated by the presence of anti-HLA-A33 and anti-HLA-B58 antibodies, as well as drug-induced hemolytic anemia caused by piperacillin drug antibody. The condition is more complicated under the influence of dual immune antibodies. Laboratory detection techniques such as platelet antibody and drug antibody tests can assist in early clinical diagnosis. At the same time, more active drug and blood transfusion treatments should be given in clinical practice to improve the prognosis.

Objective: To investigate the clinical symptoms, laboratory tests, and treatment strategies of a case of fetal/neonatal alloimmune thrombocytopenia (FNAIT) complicated with piperacillin drug antibody. Methods: The platelet antibodies in the mother were screened and identified by ELISA. The HLA antigens of the newborn were genotyped through PCR-SSO, while the specificity of HLA antibodies in the mother was determined using a Single Antigen kit. The drug antibody was detected by a piperacillin kit. Results: Maternal antibodies against paternally-derived platelet antigens were detected. The HLA genotypes of the newborn were identified as HLA A 33∶03 and HLA B 58∶01. The mother exhibited strong positive antibodies against the specific platelet antigens of the newborn, namely anti-HLA-A33 and anti-HLA-B58 antibodies. The piperacillin antibody was detected in the newborn. Following treatment of continuous intravenous immunoglobulin (IVIG), platelet transfusions, red blood cell transfusions and discontinuation of piperacillin treatment, the platelet count and hemoglobin levels increased in the newborn. Conclusion: The newborn in this case was diagnosed with FNAIT complicated by the presence of anti-HLA-A33 and anti-HLA-B58 antibodies, as well as drug-induced hemolytic anemia caused by piperacillin drug antibody. The condition is more complicated under the influence of dual immune antibodies. Laboratory detection techniques such as platelet antibody and drug antibody tests can assist in early clinical diagnosis. At the same time, more active drug and blood transfusion treatments should be given in clinical practice to improve the prognosis.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Intergenerational transmission exists within families, which is considered as key factor influencing individual health. Previous studies of intergenerational transmission were diverse and fragmented, in which the impacts of parental health-related characteristics and health risk behaviors on their children and grandchildren were reported, yet there is a lack of systematic reviews based on high-quality epidemiological research. From a population-based cohort perspective, this paper summarizes the theoretical foundations, designs and contents, outcomes, and statistical approaches of research of intergenerational transmission of health to provide theoretical support for the research in this field.

Aimed to find a safe and effective drug to replace nitroimidazole drugs in aquaculture pro-duction for the prevention and treatment of Trichomoniasis in pigeons,which can improve the eco-nomic benefits of meat pigeon breeding and ensure food safety.Firstly,Trichomonas was isolated and cultured from the crop of diseased pigeons and identified.After stable passage,a quantitative method for in vitro detection of Trichomonas was established by combining an automated cell counter and quantitative real-time PCR technology.To prepared the drug,powders of Sophora fla-vescent and Philodendron were made into herbal water extracts(SFPA)and mixed with copper sulfate(CS)solution.Then added the drug to the culture medium of Trichomonas to determine the effective concentration of it.A total of 135 pairs each of Silver King and Mimas breeding pigeons in the same laying period were selected and randomly divided into three groups,with 6 replicates in each group and 15 pairs of breeding pigeons in each replicate.Four days before brooding,the three groups were fed with 200 mL of pure water,0.5 g/L metronidazole(MDZ)solution,and a mixed solution of 30 g/L SFPA and 0.5 g/L CS,respectively.The feeding experiment lasted for 26 d.Results showed that the mixed solution of SFPA and CS had a significant killing effect on Trichomonas in vitro(P＜0.05).Feeding the drug to breeding pigeons significantly reduced the in-fection rate of breeding pigeons by Trichomonas(P＜0.05).The drug had no significant effect on the serum biochemical indexes,antioxidant properties,immunoglobulin levels of breeding pigeons,the average cage weight,immune organ indexes,meat quality and slaughter performance of squabs(P＞0.05).The results suggested that adding SFPA and CS to pigeons can effectively prevent and treat Trichomoniasis and improve production performance.It can replace nitroimidazole drugs without affecting the immune level of breeding pigeons and the weight,immune level,slaughter performance and meat quality of squabs,thereby reduce drug residues in poultry products and en-hance the food safety.

Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.