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 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 Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4⁺CXCR5⁺IFN-γ⁺Tfh1 cells, CD4⁺CXCR5⁺IL-17A⁺Tfh17 and CD4⁺CXCR5⁺IL-21⁺Tfh21 cells, and a significant decrease in the percentage of CD4⁺CXCR5⁺IL-10⁺Tfh10 cells and CD4⁺CXCR5⁺FOXP3⁺Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Animals ; Mice ; Dermatitis, Atopic/drug therapy* ; Interleukin-17 ; T Follicular Helper Cells ; Janus Kinase 2 ; Dinitrochlorobenzene ; Inflammation ; Cell Differentiation ; Signal Transduction

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM_2.5， PM₁₀， SO₂， NO₂， O₃ and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM_2.5， PM_10， SO₂ and NO₂ were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P<0.05）. PM_2.5， PM₁₀ and NO₂ were negatively correlated with the changes of lung function FEF_25%， FEF_50%， FEF_75%， FeF_25%-75%， PEF， FVC， FEV1 and FEV1/FVC， and the effect was reflected in lag0 to lag3 days （P<0.05）. The results of the dual pollutant model showed that the concentration changes of SO₂ and NO₂ were significantly correlated with the decrease of FEV1 when combined with O₃ or PM_2.5 （P<0.01）， and the concentration changes of PM_2.5 was significantly correlated with the increase of FeNO when O₃， SO₂ and NO₂ were combined respectively （P<0.01）. The effects of the dual pollutant model were greater than the effect of PM_2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer， it still has an impact on children’s respiratory tract function index and inflammation index， and the combined effect of dual pollutants is more significant than that of single pollutant.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective:To explore the effect of comfort nursing intervention in hospice care for advanced cancer patients at home, and to provide reference for hospice care for advanced cancer patients at home.Methods:A randomized controlled trial was conducted. A total of 105 patients with advanced cancer who were treated in the Cancer Hospital Affiliated to Harbin Medical University from January to February 2023 were selected as the research objects. According to the random number table, they were divided into control group of 53 cases and intervention group of 52 cases. The control group received routine nursing methods, while the intervention group received comfort nursing interventions on this basis. The intervention lasted for 4 weeks. The changes in palliative care outcomes, quality of life and death anxiety were compared between the two groups before and after intervention.Results:Totally 105 cases were included, 53 cases in the control group and 52 cases in the intervention group. In the control group, there were 25 males, 28 females, aged (58.96 ± 10.71) years old; in the intervention group, there were 22 males, 30 females, aged (59.82 ± 10.53) years old. Before intervention, there was no statistically significant difference in palliative care outcomes, quality of life and cancer death anxiety scores between the two groups of patients (all P>0.05). After intervention, the total score of palliative care outcomes in the intervention group was (13.34 ± 5.88) points, significantly lower than (16.15 ± 5.72) points in the control group, with a statistically significant difference ( t = 2.48, P<0.05). The overall health status score of quality of life was (68.55 ± 9.34) points in the intervention group, higher than (63.01 ± 9.28) points in the control group ( t = 3.05, P<0.05). The total score of cancer death anxiety was (8.85 ± 2.72) points, significantly lower than (10.59 ± 3.14) points of the control group, with a statistically significant difference ( t = 3.04, P<0.05). Conclusions:The application of comfort nursing mode in home based hospice care can improve the quality of hospice care for advanced cancer patients, reduce their level of death anxiety, and is of great significance for improving the quality of life of advanced cancer patients.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.