OBJECTIVE To systematically review the status on pharmacist competency assessment tools both domestically and internationally， providing a theoretical basis for constructing scientific and applicable pharmacist competency assessment tools in China. METHODS Through literature review and comparative analysis， 15 representative domestic and international pharmacist competency assessment tools were systematically summarized， and their theoretical foundations， core dimensions， methodological characteristics and practical applications were compared and implications were given. RESULTS &CONCLUSIONS International research has established relatively mature evaluation systems. Represented by those developed from the United Kingdom， the United States， and the International Pharmaceutical Federation， these assessment tools demonstrate scientific structure， wide application， and dynamic and international applicability. While domestic research has progressed in sub-specialties such as clinical pharmacists， licensed pharmacists and pediatric pharmacists， it still faces challenges including insufficient standardization， inadequate validation， delayed updates， and limitations in practical application. The reasons for the disparities in assessment tools between China and other countries include differences in pharmaceutical care models， varying pharmacist training systems， cultural and social background factors， as well as differences in industry management and international influence. Based on this， the author suggests promoting the development and research of assessment tools for pharmacist job competency in China from four aspects： mechanism construction， system refinement， standardization development， and practical implementation.

Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.