Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Objective: To evaluate the safety of the simultaneous administration of diphtheria, tetanus and acellular pertussis combined vaccine (DTaP) and group A and C meningococcal polysaccharide vaccine (MPSV-AC), so as to provide a scientific reference for vaccination strategies among school age children. Methods: Vaccination data and adverse reaction data for 2025 were collected from the Fujian Provincial Immunization Program Information Management System and the National Immunization Program Information System. The Chi-square test and Poisson regression model were used to compare the risk of adverse reactions between concurrent and separate vaccination. Results: In 2025, a total of 90 854 doses of DTaP were administered to children who turned 6 years old, with 107 adverse reactions reported, yielding an adverse reaction reporting rate of 117.77 per 100 000. A total of 95 913 doses of MPSV-AC were administered, with 50 adverse reactions reported, yielding an adverse reaction reporting rate of 52.13 per 100 000. All adverse reactions following DTaP and MPSV-AC vaccination in children were common reactions, predominantly local redness, swelling, and induration, with no reported abnormal reactions. The reported rate of common reactions was 112.91 per 100 000 in the concurrent DTaP+MPSV-AC group; in the separate groups, the reported rates of common reactions were 120.75 per 100 000 for DTaP and 17.92 per 100 000 for MPSV-AC, with statistically significant difference ( χ 2=46.23, P < 0.01 ). The risk of common adverse reactions in the simultaneous vaccination group did not differ significantly from that in the DTaP only group ( RR =1.07, P =0.74), but was significantly lower than that in the MPSV-AC only group ( RR =0.16, P <0.01). The risks of fever (11.58 per 100 000), pruritus, rash, myalgia, gastrointestinal symptoms, and other symptoms (23.16 per 100 000) in the simultaneous vaccination group were not significantly different from those in either single vaccine group ( RR-DTaP =0.92, 1.84, RR-MPSV-AC =0.56, 0.35, both P >0.05). The two most frequently reported reactions in both the simultaneous vaccination and DTaP only groups were local redness/swelling (95.54 per 100 000 and 117.20 per 100 000) and induration (31.85 per 100 000 and 42.62 per 100 000) at the injection site. In the simultaneous vaccination group, 92.50% of clinical symptoms occurred within 48 h, and the risks of occurrence at <24 h, 24-<48 h , and ≥48 h were not significantly different from those in the DTaP only group ( RR =1.00, 0.98, 1.43, all P >0.05). Conclusion The simultaneous administration of DTaP and MPSV-AC does not increase the risk of adverse reactions and may serve as a reference for administering both vaccines concurrently in children aged 6 years.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Objective To analyze the clinical characteristics and prognostic factors of patients with double hit multiple myeloma(MM)patients with p53 deletion/mutation.Methods MM patients admitted to Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from June 2017 to June 2023 were selected as the study subjects.They used fluorescence in situ hybridization(FISH)to detect chromosomal changes and gene sequencing to detect p53 gene mutations.According to the detection results,a total of 180 patients with p53 deletion/mutation were selected,and these 180 patients were divided into a p53 deletion/mutation-only group(control group,n=73)and a dual strike group with p53 deletion/mutation(research group,n=107).Compared the clinical characteristics and efficacy of two groups of patients,and analyzed the factors influencing the prognosis of MM patients.Established a risk-scoring model for evaluating and validating the prognosis of MM patients.Results The proportion of patients with extramedullary lesions(46.73%),bone lesions(42.06%),DS stage III(70.09%),ISS stage III(64.49%)and R-ISS stage III(59.81%)in research group with p53 deletion/mutation was significantly higher than that in conctrol group(28.77%,19.18%,45.21%,39.73%,32.88%),and the differences were statistically significant(χ2=5.861～12.600,all P<0.05).The OR of patients in research group with p53 deletion/mutation after treatment was 52.34%,lower than 65.75%in conctrol group.Still,there was no statistically significant difference between the two groups(χ2=3.202,P=0.074).The PFS and OS of MM patients with research group were significantly shorter than those with conctrol group,and the differences were statistically significant(χ2=15.522,16.973,all P＜0.05).Multivariate COX proportional hazards results,bone marrow plasma cell ratio≥30%,β2-MG≥5.5mg/L,PLT<125×109/L,LDH≥240U/L and dual strikes with p53 deletion/mutation were risk factors for PFS rate in MM patients(Wald χ2=2.983～3.942,all P＜0.05).R-ISS stage III,bone marrow plasma cell ratio≥30%,β2-MG≥5.5mg/L,LDH≥240U/L and dual strikes with p53 deletion/mutation were risk factors for OS rate in MM patients(Wald χ2=3.389～3.971,all P＜0.05).Establishing a risk scoring model for evaluating the prognosis of MM patients,and the ROC curve results show that the risk scoring model has good discrimination.The 2-year PFS and OS were shortened sequentially in the low-risk group,medium-risk group and high-risk group,and the differences were statistically significant(F=23.629,17.664,all P<0.05).Conclusion The clinical manifestations of MM patients with double-hit p53 deletion/mutation are mainly extramedullary lesions,bone lesions,DS staging,ISS staging,and R-ISS staging,with stage III being the most common.The double-hit of p53 deletion/mutation and accompanying is an important prognostic factor for MM patients.

Objective:To explore latent categories and influencing factors of disease uncertainty in atrial fibrillation patients undergoing radiofrequency ablation (RFA) .Methods:Convenience sampling was used to select 346 atrial fibrillation patients who underwent RFA from February 2022 to July 2024 at China-Japan Union Hospital of Jilin University. Patients were surveyed using the General Information Questionnaire, Mishel Uncertainty in Illness Scale-Adult Form (MUIS-A), Brief Illness Perception Questionnaire, Chinese version of the Sense of Coherence-13, and Family APGAR Index. Latent categories and influencing factors of disease uncertainty in atrial fibrillation patients with RFA were explored using latent profile analysis and Logistic regression analysis.Results:A total of 346 questionnaires were distributed and 328 valid questionnaires were recovered, with a valid recovery rate of 94.80% (328/346). The total MUIS-A score for 328 patients with atrial fibrillation was (97.06±9.41). Three latent categories of disease uncertainty existed in 328 atrial fibrillation patients with RFA, namely high-level disease uncertainty group ( n=138), intermediate-level disease uncertainty group ( n=120), and low-level disease uncertainty group ( n=70). Age, education level, number of RFA, type of atrial fibrillation, perception of disease, sense of coherence, and family care were the factors influencing the disease uncertainty in patients with atrial fibrillation ( P<0.05) . Conclusions:Disease uncertainty after RFA in patients with atrial fibrillation is above the intermediate level. Nursing staff should provide precise interventions for patients with different latent categories of disease uncertainty in conjunction with its influencing factors.

Objective:To explore the developmental trajectories of care dependency in patients after percutaneous coronary intervention (PCI) and to identify its influencing factors.Methods:A convenience sampling method was used to recruit patients who underwent PCI at China-Japan Friendship Hospital of Jilin University from August 2023 to July 2024. The Chinese version of the Care Dependency Scale was administered at 1 week, 1 month, 3 months, and 6 months postoperatively. A latent growth mixture model was employed to identify trajectories of care dependency. Logistic regression analysis was used to examine the influencing factors.Results:A total of 397 questionnaires were distributed, and 389 valid questionnaires were returned, with a response rate of 97.98% (389/397). Three distinct trajectories of care dependency were identified among the 389 patients: stable low dependency, recovering high dependency, and persistent high dependency. Age, cardiac function classification, number of comorbidities, frailty, self-efficacy, and utilization of chronic disease resources were significantly associated with different trajectory classes ( P<0.05) . Conclusions:Care dependency after PCI exhibits heterogeneity in its developmental trajectories. Patients in the persistent high-dependency group represent a high-risk subgroup requiring special attention. Nursing staff should enhance their ability to recognize trajectory patterns and implement precise interventions based on trajectory type and influencing factors.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Objective:To explore and discuss the ethical issues and challenges arising from the rapid development of digital intelligence technology in medical research, and to propose strategies for addressing them.Methods:By reviewing the applications of big data, artificial intelligence, and other technologies in medical research, as well as the related ethical issues, discussions and analyses were conducted on aspects such as informed consent, privacy protection, data security, and algorithmic bias.Results:To address the numerous ethics issues and challenges in medical research in the digital intelligence era, researchers and institutions should actively respond with a stance of inclusivity and prudence.Conclusions:By improving the informed consent process, strengthening legal and policy frameworks, promoting interdisciplinary collaboration, and establishing risk assessment mechanisms, we can promote the continuous innovation and high-quality development of medical knowledge and practice.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins