ObjectiveTo predict the mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer via network pharmacology and validate the prediction results in animal experiments. MethodsThe potential mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer was predicted by network pharmacology， liquid chromatography-mass spectrometry （LC-MS）， and molecular docking methods. C57/BL6 mice were assigned into normal， model， cisplatin， and Shasheng Maidong Tang+cisplatin groups. In addition to the normal group， the remaining groups were injected subcutaneously with 0.2 mL of 1×10⁷ cells·mL^-1 Lewis lung cancer cells to establish the Lewis lung cancer model. The daily gavage dose of Shasheng Maidong Tang was 3.58 g·kg^-1， and the concentration of cisplatin intraperitoneally injected on every other day was 2 mg·kg^-1. Drugs were administered for 14 d. The changes in the tumor volume and the rate of tumor suppression were monitored， and the tumor histopathological changes were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay was employed to measure the interleukin （IL）-6 and interferon （IFN）-γ levels in peripheral blood. Real-time PCR was performed to quantify the mRNA levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription 1 （STAT1）， and signal transducer and activator of transcription 3 （STAT3） in the tumor tissue of mice. Western blot was employed to determine the protein levels of JAK2， STAT3， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， and Pim-1 proto1 （PIM1） in the tumor tissue. Immunohistochemistry was employed to detect the expression of Bcl-2 and PIM1 in the tumor tissue. ResultsNetwork pharmacological predictions indicated that Shasheng Maidong Tang might enhance the efficacy of chemotherapy for lung cancer by regulating nitrogen metabolism， AGE-RAGE signaling pathway， cancer pathway， and JAK/STAT signaling pathway. The experimental results demonstrated that tumor volume in the cisplatin group and Shasheng Maidong Tang+cisplatin group was reduced compared with the model group， with statistically distinct differences observed on days 14， 17， 20 post modeling （P<0.05）. Notably， the Shasheng Maidong Tang+cisplatin therapy further decreased tumor volume compared with the cisplatin group， showing marked reductions on days 17 and 20 （P<0.05）， consistent with trends visualized in tumor volume comparison charts. The Shasheng Maidong Tang+cisplatin group exhibited higher tumor inhibition rate than the cisplatin group （P<0.05）. Histopathological analysis via HE staining revealed that the tumors in the model group displayed frequent nuclear mitosis， densely arranged cells， hyperchromatic nuclei， and no necrosis. Cisplatin treatment induced partial necrosis and vacuolization， while the Shasheng Maidong Tang+cisplatin group exhibited extensive necrotic regions， maximal vacuolization， disarranged tumor cells， and minimal mitotic activity. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed elevated level of IFN-γ （P<0.01） and declined level of IL-6 （P<0.01） in the peripheral blood. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented elevated level of IFN-γ （P<0.01） and lowered level of IL-6 （P<0.01） in the peripheral blood. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin groups showed down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level STAT1 （P<0.01）. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level of STAT1 （P<0.01）. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， and STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. Compared with the cisplatin group， Shasheng Maidong Tang+cisplatin group presented down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. The Bcl-2 and PIM1 expression results obtained by immunohistochemistry were consistent with those of Western blot. ConclusionShasheng Maidong Tang may enhance the efficacy of chemotherapy in the mouse model of Lewis lung cancer by regulating the JAK2/STAT3 signaling pathway.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To explore the impact of multi-model adaptive statistical iterative reconstruction (ASiR-V) algorithm on radiation dose and image quality in children’s ultra-low-dose chest CT examination. Methods A total of 72 children who underwent chest CT scans at Qingdao Municipal Hospital with admissions between January 2024 and January 2025 were selected as subjects and divided into two groups using a random number table. In the control group (n = 36), the tube voltage was set at 100 kVp and the conventional filtered back projection algorithm was used. In the observation group (n = 36), the tube voltage was set at 80 kVp and images were reconstructed using 30% ASiR-V (observation group 1), 60% ASiR-V (observation group 2), and 90% ASiR-V (observation group 3), respectively. Radiation doses were recorded for each group, and both subjective and objective evaluations of image quality were conducted. Results Compared with the control group, the observation group demonstrated significantly lower volume CT dose index [(0.86 ± 0.09) mGy], dose length product [(25.90 ± 3.55) mGy·cm], and effective dose [(0.01 ± 0.001) mSv] (P < 0.05). There was no significant difference in subjective evaluation scores of image quality among the four groups (z = −2.206, P = 0.530). Additionally, Fisher’s exact test showed that the proportion of images scoring 4-5 points was higher in observation group 2 than in observation group 3 (P = 0.024). The noise value of the ascending aorta in the mediastinal window and the noise values of the right and left middle lung fields and the right and left upper lung fields in the lung window were lower in observation groups 2 and 3 than in the control group, and these values were lower in observation group 3 than in observation group 2 (P < 0.05). The signal-to-noise ratios of the ascending aorta and liver in observation groups 2 and 3 were higher than those in the control group, and the ratios were higher in observation group 3 than in observation group 2 (P < 0.05). Conclusion Reconstruction using the 60% ASiR-V algorithm for pediatric ultra-low-dose chest CT examination can ensure good image quality while reducing radiation dose and improving examination safety.

OBJECTIVE To explore the practice pathway and evaluate the effectiveness of the resident pharmacists stationed in the Drug Clinical Trial Institution Office （hereinafter referred to as the “GCP resident pharmacist”） in the management of dermatological drug clinical trials. METHODS The practical approach of GCP resident pharmacists participating in dermatological drug clinical trials at our hospital was introduced. A retrospective analysis was conducted on the data of dermatological drug clinical trials from 2021 to 2024， comparing efficiency and quality indicators between dermatological clinical trials and those of other specialties. RESULTS With the involvement of our hospital’s GCP resident pharmacists throughout, the process for dermatology drug clinical trials was constructed and optimized， a dedicated quality control system was established， and the acceleration strategy for subject enrollment was optimized. The number of dermatological drug clinical trials at our hospital showed a compound annual growth rate of 69.56% from 2021 to 2023. In terms of efficiency indicators， the approval waiting time for dermatological drug clinical trials was （12.31±4.99） days， which was significantly shorter than that of other specialties （[ 19.68±6.09） days， P＜0.05]. Regarding quality indicators， the enrollment rate for dermatological drug clinical trials was 75.71%（50.00%，114.48%）， which was significantly higher than that of other specialties [51.00%（25.00%，174.17%）， P＜0.05]. The numbers of first quality control issues （[ 8.31±3.25）items vs.（ 11.68±4.49）items] and protocol deviations [5.5（2.0，11.0）times vs. 11.0（5.5，17.5）times] were significantly lower than those of other specialties （P＜0.05）. CONCLUSIONS GCP resident pharmacists significantly enhance the overall efficiency of dermatological drug clinical trials， playing a crucial role in ensuring the reliability and authenticity of drug clinical trials， as well as safeguarding the rights and safety of trial subjects.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective:To investigate the influence of prealbumin on cerebral infarction severity, hemorrhage transformation and 1-year prognosis.Methods:A retrospective study was conducted to select 752 patients with cerebral infarction who were treated in Beijing Tiantan Hospital,Capital Medical University from December 2018 to December 2019 as the study objects. Personal information and laboratory indicators of the patients were collected including prealbumin, hemoglobin, white blood cell count, etc.Patients were divided into group B1 (<238 mg/L) and group B2 (≥238 mg/L) based on median prealbumin. By inquiry patient's case, NIHSS score (<16 was classified as mild, ≥16 as moderate and severe)and cerebral infarction volume (<20 cm 3 as small infarct, >20 cm 3 as large infarct) were recorded to evaluate the severity of the disease, and whether hemorrhage transformation occurred during hospitalization was recorded. Patients were followed up 1 year after discharge, and prognostic information of patients was recorded, including neurological function recovery (mRS score <3 was classified as good recovery, ≥3 as poor recovery),all-cause case fatality rate, and recurrence of cardio-cerebrovascular events. Normally distributed measurement data were expressed as xˉ±s, non-normally distributed measurement data were expressed as median and quartiles[ M( Q1, Q3)], categorical variable were expressed as ratio and percent(%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. Chi-square test were used on comparison between groups of categorical variable. Single-factor comparison, Spearman correlation analysis and multiple Logistic regression were used to analyze the correlation between prealbumin and other laboratory indicators, cerebral infarction severity, hemorrhage transformation and 1-year prognosis, respectively. Results:The NIHSS score and infarct volume of patients in group B1 were 5(2,10) and 3.18(0.72,18.00) cm 3, and those in group B2 were 3(2,7) and 2.0(0.5,10.0) cm 3, respectively, which were higher in group B1 than in group B2, the differences were statistically significant ( Z=3.85, P<0.001, Z=2.81, P=0.005). The proportion of mRS Score ≥3 in group B1 was 28.8%(107/371), and the all-cause case fatality rate was 7.5%(28/371), both higher than 20.5%(78/381) and 3.1%(12/381) in group B2, with statistical significance ( χ2=7.10, P=0.008, χ2=7.22, P=0.007). Hemorrhage transformation and recurrence of cardio-cerebrovascular events were 13.5%(50/371) and 11.6%(43/371) in group B1 and 9.2% (35/381) and 8.7%(33/381) in group B2, respectively, with no significant difference between the two groups ( χ2=3.45, P=0.063, χ2=1.78, P=0.183). Multivariate logistic regression analysis showed that, after adjusted for potential confounding factors, prealbumin was protective factor of NIHSS ( OR and 95% CI: 0.990(0.984-0.997), P=0.035), poor neurological recovery(mRS≥3) ( OR and 95% CI:0.992(0.988-0.997), P<0.001) and all-cause case fatality rate ( OR and 95% CI:0.991(0.983-0.999), while prealbumin had no significant influence on cardiocerebrovascular recurrence events ( OR and 95% CI: 0.999(0.993-1.005), P=0.729). Conclusion:Prealbumin is significantly associated with the severity of cerebral infarction and poor prognosis 1 year after discharge, and low prealbumin was an independent risk factor for NIHSS score(≥16), poor neurological recovery (mRS≥3) and all-cause case fatality rate.