OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

ObjectiveTo investigate the effects of Yishen Juanbi pills （YSJB）-containing bone marrow fluid on the migration and differentiation phenotypes of CD4⁺T lymphocytes based on the stromal cell-derived factor-1/chemokine receptor 4 （SDF-1/CXCR4） signaling pathway. MethodsPrimary CD4⁺T lymphocytes were isolated from mice using magnetic bead separation and identified for purity by flow cytometry. A CD4⁺T lymphocyte culture system was then established to observe the effects of SDF-1 on CD4⁺T-cell migration and differentiation. On this basis， the experimental groups included the Sham group， the ovariectomy （OVX） group， the Sham+collagen-induced arthritis （CIA） group， the OVX+CIA group， the Sham+CIA+YSJB group （2.16 g·kg^-1）， the OVX+CIA+YSJB group （2.16 g·kg^-1）， and the OVX+CIA+methotrexate （MTX） group （1.5 mg·kg^-1）. Bone marrow fluid from each group was prepared according to previous methods and added to the CD4⁺ T-cell culture system at 5% （v/v）. Transwell assays were used to examine CD4⁺T-cell migration in each group. Real-time PCR was used to measure the mRNA expression levels of interleukin （IL）-17， tumor necrosis factor-α （TNF-α）， retinoic-acid-related orphan receptor γt （RORγt）， IL-10， transforming growth factor-β （TGF-β）， forkhead box P3 （FoxP3）， CXCR4， phosphoinositide 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot was used to detect the expression of helper T （Th）17/regulatory T （Treg） cell signature factors （RORγt， FoxP3）， CXCR4， PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. In a separate set of experiments， cells were divided into the Sham group， OVX+CIA group， OVX+CIA+CXCR4 antagonist AMD3100 group， and OVX+CIA+YSJB+AMD3100 group to observe changes in the above indicators following AMD3100 intervention. ResultsCompared with the Sham group， the number of migrated cells in the lower chamber was significantly increased in the Sham+CIA and OVX+CIA groups （P<0.05， P<0.01）. The mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was significantly upregulated， whereas FoxP3， IL-10， and TGF-β mRNA expression was significantly decreased （P<0.05， P<0.01）. Protein expression of RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt was significantly increased， while FoxP3 protein expression was markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA group， the OVX+CIA+YSJB group and OVX+CIA+MTX group showed significantly reduced migration （P<0.05）， mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was also significantly decreased， while FoxP3， IL-10， and TGF-β mRNA expression was significantly increased （P<0.05， P<0.01）. RORγt protein expression was significantly downregulated， and FoxP3 protein expression markedly upregulated （P<0.05）. In the OVX+CIA+YSJB group， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was significantly decreased （P<0.05）. Compared with the OVX+CIA group， RORγt， CXCR4， PI3K， and Akt mRNA expression in CD4⁺T cells was significantly decreased in the OVX+CIA+AMD3100 group and the OVX+CIA+YSJB+AMD3100 group， while FoxP3 mRNA and protein expression was significantly upregulated （P<0.05， P<0.01）. RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was also markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA+AMD3100 group， the OVX+CIA+YSJB+AMD3100 group showed significantly decreased RORγt and Akt mRNA expression （P<0.05） and significantly lower p-Akt/Akt protein expression （P<0.05）. ConclusionYSJB-containing bone marrow fluid suppresses CD4⁺T-cell migration and regulates Th17/Treg balance by downregulating Th17-associated signature factors and upregulating Treg-associated signature factors through inhibition of the SDF-1/CXCR4 signaling pathway and PI3K/Akt signaling pathway. The SDF-1/CXCR4 signaling pathway is one of the targets through which YSJB inhibits CD4⁺T-cell differentiation.

Extracellular vesicles (EVs) are membrane-bound vesicles secreted by cells, including exosomes, microvesicles, and apoptotic bodies, which play critical roles in intercellular communication, material transport, and signal transduction. In recent years, increasing evidence has highlighted the essential function of EVs in early embryo development. By carrying bioactive molecules such as proteins, nucleic acids (e.g., mRNA and miRNA), and lipids, EVs regulate embryonic gene expression, cell proliferation, differentiation, and the microenvironment. Studies have shown that EVs derived from various segments of the female reproductive tract can enhance embryonic developmental potential, improve embryo quality, and facilitate implantation. Additionally, EVs secreted by embryos themselves participate in intercellular communication and play pivotal roles during embryogenesis. This review summarizes recent advances in understanding the functions of EVs in early embryo development, discusses their roles in mediating cell-cell communication and regulating gene expression, and explores their potential applica-tions in reproductive medicine and clinical practice, offering new perspectives for optimizing assisted reproductive technologies.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Objective To understand the latent profiles of kinesiophobia in kidney transplant recipients and explore the influencing factors of different profiles.Methods A cross-sectional study was conducted on 230 kidney transplant recipients subjected with convenient sampling from Department of Nephrology,the First Affiliated Hospital of Army Medical University from November 2024 to February 2025.General Information Questionnaire,Tampa Scale of Kinesiophobia-11(TSK-11),Exercise Compliance Questionnaire,Fatigue Scale-14(FS-14),Patient Health Questionnaire-9(PHQ-9)and Chinese Version of the Self-Efficacy to Manage Chronic Disease Scale(C-SEMCD)were used for investigation and latent profile analysis.Univariate analysis and logistic regression analysis were applied to explore the influencing factors of different profiles.Results Kinesiophobia in the participants was classified into 3 latent profiles:fearless movement type-low kinesiophobia group(54 cases,23.48%),cautious movement type-moderate kinesiophobia group(98 cases,42.61%),and resistant movement type-high kinesiophobia group(78 cases,33.91%).Statistical differences were observed among the 3 groups in terms of age,education level,post-operative duration,depression score,fatigue score,and self-efficacy score of chronic disease management(P<0.05).Logistic regression analysis showed that age(OR=8.82,95%CI:1.27～61.10),education level[junior high school or below(OR=0.14,95%CI:0.04～0.50);technical secondary school or senior high school(OR=0.08,95%CI:0.02～0.27)],post-operative duration[<1 year(OR=11.39,95%CI:2.53～51.30);1-5 years(OR=11.05,95%CI:2.48～49.22)],fatigue(OR=1.32,95%CI:1.10～1.59),and depression(OR=1.53,95%CI:1.19～1.98)were influencing factors for resistant movement type-high kinesiophobia in the kidney transplant recipients.Education level(technical secondary school or senior high school:OR=0.32,95%CI:0.12-0.86)and self-efficacy of chronic disease management(OR=0.95,95%CI:0.90-1.00)were influencing factors for cautious movement type-moderate kinesiophobia in the recipients.Conclusion Kinesiophobia in kidney transplant recipients can be classified into 3 latent profiles.Recipients'age,education level,post-operative duration,fatigue,and depression are influencing factors for the resistant movement type-high kinesiophobia,and education level and chronic disease management self-efficacy are important influencing factors for the cautious movement type-moderate kinesiophobia.

Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

Objective: To analyze the impact of parental sports concept and behavior on physical activity in preschool children, so as to provide a foundation for future guidance on fostering childrens physical activity within the family context. Methods: From November to December 2020, a clustered convenience sampling method was employed to conduct surveys, and a total of 283 children were selectal from one kindergarten each in Beijing, Shenyang, and Xian. Participating children wore ActiGraph GT9X accelerometers continuously for one week to collect data on different intensity levels of physical activity. Physical Activity afterschool Questionnaire for Preschooler (P-PAQ) was utilized to assess parental sports concept and behavior. The gender differences in physical activity level and physical activity compliance rate were analyzed by using ttest, Mann-Whitney U test, and Chisquare test; and the relationship between parental exercise concepts and behaviors and physical activity of preschool children was analyzed using Spearman rank correlation analysis and multiple linear regression analysis. Results: Parental sports concept was significantly positively correlated with average daily moderatetovigorous physical activity (MVPA) and total physical activity (TPA) in children (r=0.12-0.16, P<0.05). Parental sports behavior was significantly positively correlated with childrens average daily TPA (r=0.25, P<0.05). Multiple linear regression revealed that parental sports concept was positively correlated with average daily MVPA and TPA in both boys and girls (B=0.65-0.83), while parental sports behavior only was positively correlated with boys average daily MVPA and TPA (B=0.24-0.25)(P<0.05). Conclusions Parental sports concept and behavior can impact physical activity levels in preschool children, exhibiting gender differences. Future guidance on physical activity in family upbringing should consider both parental sports concept and behavior, and pay attention to the influence of childrens gender.

Objective To investigate the value of single photon emission computed tomography/computed tomography(SPECT/CT)fusion imaging for post-implantation dose verification of 125I particles in patients with bone metastases.Methods Forty patients with metastatic bone tumors treated with 125I particles implantation were selected.Within 24 h after 125I particles implantation,patients underwent SPECT/CT fusion imaging and the radioactivity per unit(RPU)was calculated.The treatment planning system(TPS)was then used to obtain the isodose profiles of SPECT/CT fusion imaging results and to calculate the tumor target coverage.The patient's preoperative and postoperative 1 month clinical outcomes,including local tumour remission,pain assessment,quality of life and serum alkaline phosphatase(ALP)levels were compared,and a receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of tumor target coverage on postoperative outcomes.Results The mean number of particles implanted in the target area was 32.52±12.87.Within 24 h of 125I particles implantation,SPECT/CT fusion imaging analysis confirmed a strong positive correlation between the RPU of the radioactive concentration area and the mean dose received by the patient(r=0.786,P<0.05).The predicted area under the curve(AUC)for local tumor remission,pain relief,quality of life improvement and change in ALP levels was 0.789,0.757,0.804 and 0.833,respectively.Conclusion SPECT/CT fusion imaging can be used for postoperative dose verification of 125I particles for metastatic bone tumors and has some predictive value for clinical outcomes.

Objective:To investigate the correlation between plasma total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn), neurofilament light chain(NfL) and subtypes of Parkinson disease(PD).Methods:A total of 62 PD patients admitted to the Department of Neurology, the Affiliated Huai 'an No. 1 People 's Hospital of Nanjing Medical University from September 2021 to January 2023 were selected and scored on the Hoehn-Yahr stage(H-Y), unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ), levodopa equivalent daily dosage(LEDD), mini-mental state examination(MMSE), Parkinson disease quality of life questionnaire(PDQ-39) and activities of daily living(ADL). During the same period, 25 healthy individuals matched in age and sex were enrolled as the control group (HC). Clinical characteristics and blood samples were collected. The plasma levels of α-syn, p-α-syn and NfL were detected by enzyme-linked immunosorbent assay(ELISA). PD patients were divided into tremor dominant type (TD, n=27) and akinetic-rigid dominant type (AR, n=35) based on UPDRS-Ⅲ scores. Multifactorial Logistic regression analysis was performed by SPSS 25.0 software to determine the influencing factors of subtypes of Parkinson disease. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of plasma NfL between the AR type and the TD type. Results:Plasma α-syn, p-α-syn, NfL levels in the PD group were significantly higher than those of the HC group ( Z=-2.537, -6.580, -7.101, all P<0.05). There were statistically significant differences between the AR type and the TD type in disease duration, H-Y stage, UPDRS-Ⅲ scores, LEDD and MMSE scores ( Z=-2.503, -3.021, -2.025, -2.086, -2.409, all P<0.05). While no significant difference was found in plasma α-syn and p-α-syn levels between the AR type and TD type ( Z=-0.341, -0.085, both P>0.05), the plasma NfL levels were notably higher in the AR type(92.79(16.84, 117.53) pg/mL) compared to the TD type (12.10(6.99, 100.17) pg/mL)( Z=-2.236, P<0.05). Plasma NfL levels were correlated with rigidity scores ( r=0.438, P<0.001), UPDRS-Ⅲ scores ( r=0.337, P<0.05) and motor subtypes ( r=0.286, P<0.05) in PD patients. Multivariate Logistic regression analysis showed that NfL was risk factor for AR( B=0.002, OR=1.002, 95% CI=1.001-1.003, P=0.017). The ROC curve analysis indicated that plasma NfL levels could predict different subtypes of PD with an AUC=0.667, optimal cutoff =26.527. Conclusion:There is a correlation between elevated plasma NfL levels and the occurrence of AR type of PD, suggesting that nerve injury is probably involved in the occurrence and progression of various motor subtypes of PD.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.