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.

The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Objective:To observe the incidence of early blood eosinophils (Eos) elevation in patients with peritoneal dialysis (PD), analyze its related factors, and its relationship with early-onset peritonitis in PD patients.Methods:This study was a retrospective observational cohort study. Patients who underwent PD catheterization in Peking University People's Hospital from January 2012 to December 2022 were included. After surgery, PD treatment was started immediately and followed up regularly ≥12 months. The general information and laboratory indexes collected 1 week before catheterization, and at 1, 3, 6 and 12 months after catheterization were recorded. The occurrence of elevated blood Eos (≥0.5×10 9/L) during the early stage of PD, the related factors of Eos elevation (≥0.5×10 9/L) and the relationship with early-onset peritonitis (within 12 months after PD initiation) were analyzed. Results:(1) A total of 235 patients were enrolled, with an age of (57.9.±13.9) years, including 136 males (57.9%). The primary diseases were predominantly chronic glomerulonephritis (111/235, 42.7%) and diabetic nephropathy (83/235, 35.3%). During the 12-month follow-up period, 73 patients had elevated blood Eos (31.1%), of which 37 cases (50.7%) occurred within 1 month after PD catheterization, 21 cases (28.7%) occurred 2-3 months after PD catheterization, 12 cases (16.4%) occurred 4-6 months after PD catheterization, and 3 cases (4.1%) occurred 7-12 months after PD catheterization. In 73 patients with elevated Eos, 69 cases (94.5%) were mildly elevated, 4 cases (5.5%) were moderately elevated. As for the duration of elevated blood Eos, 28 cases (38.4%) lasted less than 1 month, 27 cases (37.0%) lasted 1-3 months, and 18 cases (24.7%) lasted more than 3 months. (2) In patients with elevated blood Eos, the proportion of male patients (71.4% vs. 52.1%, χ 2=7.515, P=0.006), the proportion of diabetes mellitus (55.7% vs. 41.2%, χ 2=4.168, P=0.046), and the proportion of combined vascular disease (32.9% vs. 18.2%, χ 2=6.060, P=0.017) were significantly higher than those patients in normal blood Eos group. (3) Multivariate Logistic regression analysis showed that male was an independent related factor for elevated blood Eos (≥0.5×10 9/L) in the early stages of PD ( OR=2.044, 95% CI 1.101- 3.794, P=0.023). (4) Diabetes mellitus ( OR=3.363, 95% CI 1.087-10.405, P=0.035), lower baseline hemoglobin level ( OR=0.941, 95% CI 0.903-0.980, P=0.004) and elevated blood Eos (with serum Eos<0.5×10 9/L as reference, OR=2.917, 95% CI 1.022-8.326, P=0.045) were the independent related factors of early-onset peritonitis. Conclusion:Blood Eos elevations are common in early stage of PD patients , mainly occuring within 6 months after PD catheterization, and most of them are slightly increased and last less than 3 months. Male sex is an independent related factor for the elevation of blood Eos in the early stage of PD. Elevated blood Eos is an independent related factor for early-onset peritonitis.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Objective:To retrieve, screen, evaluate and integrate the relevant evidence of nursing management for patent foramen ovale detected by contrast transesophageal echocardiography (cTEE) to provide a basis for clinical practice.Methods:A systematic search was conducted in relevant Chinese and English databases, guideline websites, and professional association websites such as China National Knowledge Infrastructure, Wanfang database, PubMed, and MedLink, etc. Relevant literatures on the detection of patent foramen ovale by cTEE were included, including guidelines, expert conconsensus, clinical decisions, evidence summaries, and systematic reviews. The search period was from the establishment of the database to July 31, 2024. Two evidence-based nursing researchers evaluated the quality of the literature and extracted relevant evidence in combination with clinical situations.Results:A total of 15 literatures were included. Among them, there were 3 guidelines, 6 expert consensuses, 3 clinical decisions, 2 quasi-experiments, and 1 systematic review. Thirty pieces of evidence were summarized from five aspects: assessment, education and publicity, preparation before examination, detection during examination, care after examination.Conclusions:The best evidence for the nursing management of patent foramen ovale detected by cTEE is of high quality and strong authority, which can provide evidence-based basis for standardizing clinical practice and accurately and efficiently detecting patent foramen ovale.

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 effect of cytoskeleton-associated protein 4 (CKAP4) gene knockout on maxillary expansion osteogenesis and its regulatory mechanism on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC).Methods:Nineteen wild type (WT) and nineteen CKAP4 gene knockout (Ckap4 -/-) mice aged 6-8 weeks were selected to establish a mouse model of rapid maxillary expansion. Samples were taken on the 7th and 14th day after the operation. Micro-CT and HE staining were used to evaluate bone regeneration. Tissue proteins in the modeled area were collected, and Western blotting analysis (WB) was used to detect the protein expression levels of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). BMSC were isolated from WT and Ckap4 -/- mice. The expression of surface markers CD29, Sca-1, CD44, CD45, CD34, and CD11b was detected by flow cytometry, and cell proliferation ability was detected by 5-ethynyl-2'-deoxyuridine (EdU). After 7 days of osteogenic induction, real-time fluorescence quantitative PCR (RT-qPCR) and WB were used to detect the expression levels of RUXN2, ALP, OCN, protein kinase B (AKT), and phosphorylated protein kinase B (p-AKT). After 21 days, alizarin red staining and cetyl pyridine chloride quantification were used to detect the differences in mineralized nodule formation in each group. In CKAP4 gene knockout BMSC, the small-molecule AKT agonist sc79 (4 μg/ml) was added as the intervention group (Ckap4 -/- +sc79), and dimethyl sulfoxide (DMSO) treatment was used as the control group (Ckap4 -/- +DMSO). After osteogenic induction, RT-qPCR, WB, and alizarin red staining were used to compare the osteogenic differentiation differences between the two groups of cells. Results:The micro-CT results showed that at 7 days and 14 days after surgery, the new bone volume in the Ckap4 -/- group [(0.070±0.010) and (0.146±0.019) mm 3] was significantly lower than that in the WT group [(0.094±0.006) and (0.196±0.013) mm 3] (both P<0.01). HE-stained histological sections showed that the area of new bone tissue in the Ckap4 -/- group at 7 days and 14 days after surgery [(0.101±0.008) and (0.158±0.010) mm 2] was also significantly lower than that in the WT group [(0.116±0.005) and (0.183±0.008) mm 2] (both P<0.05). WB was used to detect the tissue proteins in the maxillary modeling area of mice in the two groups 7 days after surgery. The results showed that the expression levels of ALP, RUNX2 and OCN in the Ckap4 -/- group were significantly lower than those in the WT group. BMSC from wild-type mice and CKAP4 knockout mice were both positively expressed for CD29, CD44, and Sca-1, and basically not expressed for CD45, CD34, and CD11b. EdU assay showed that there was no significant difference in the proliferation ability of cells in the two groups. After 21 days of osteogenic induction of BMSC, alizarin red staining results showed that the number of mineralized nodules in the Ckap4 -/- group was significantly less than that in the WT group. After adding sc79, the number of mineralized nodules increased significantly, which was consistent with the results of cetyl pyridine chloride quantification. After 7 days of osteogenic induction, It was found that the expression levels of ALP, RUNX2, and OCN in the CKAP4 -/-group (0.751±0.066, 0.484±0.040, 0.679±0.063) were significantly lower than those in the WT group (1.000±0.113, 1.000±0.081, 1.000±0.113) (all P<0.001). The results of WB were consistent with those of RT-qPCR. At the same time, the WB results showed that the level of p-AKT protein in the CKAP4 -/-group (0.518±0.114) was significantly lower than that in the WT group (1.000±0.234) ( P<0.05). After treatment with sc79 for 7 days of osteogenic induction, RT-qPCR was used to detect the gene expression levels of ALP, RUNX2, and OCN. The results showed that the expression levels in the CKAP4 -/-+sc79 group (2.755±0.353, 4.800±0.990, 2.524±0.137) were significantly higher than those in the CKAP4 -/-+DMSO group (1.000±0.078, 1.000±0.247, 1.000±0.175) (all P<0.001). Conclusions:CKAP4 knockout inhibits the osteogenic differentiation of BMSC by reducing the activity of the PI3K/AKT signaling pathway, thereby suppressing osteogenesis in maxillary expansion.

The blood-brain barrier(BBB)plays a crucial role in maintaining the special microenvironment of brain tissue,which promotes the exchange of substances while separating the peripheral circulatory system from the brain parenchyma.However,normal aging and neurodegenerative diseases can alter and disrupt the physiological properties of the BBB.This review provides a brief introduction to the interrelationship and pathogenic mechanisms between Alzheimer's disease(AD)and BBB dysfunction,and explores current research status and BBB-targeted pharmacotherapy for AD,providing new ideas for the prevention and treatment of AD.

Objective:To evaluate the clinical efficacy and safety of dupilumab in the treatment of pediatric prurigo nodularis (PN), and to explore factors associated with the treatment response.Methods:A retrospective analysis was conducted on clinical data from 26 children with PN who received dupilumab treatment at the Institute of Dermatology and Venereology, Sichuan Provincial People's Hospital between December 2022 and January 2025. Primary efficacy endpoints were the proportion of patients achieving investigator's global assessment-activity (IGA PN-A) and stage (IGA PN-S) scores of 0/1 at week 8; secondary efficacy endpoints included the proportion of patients achieving a ≥ 4-point reduction in the pruritus numerical rating scale (NRS) and changes in laboratory parameters. Paired t tests or Wilcoxon signed-rank tests were used for pre- and post-treatment comparisons; generalized estimating equation models were applied to evaluate changes in eczema area and severity index (EASI) scores over time; univariate logistic regression analysis was performed to calculate odds ratios ( ORs) and 95% confidence intervals ( CIs) to analyze factors influencing efficacy. Results:Among the 26 children with PN, 14 (53.8%) were males and 12 (46.2%) were females, with ages ( M[ Q1, Q3]) of 4.50 (3.00, 9.25) years and disease duration of 1.00 (0.48, 2.25) years. Twenty-four (92.3%) patients had comorbid atopic diseases, including 17 with allergic rhinitis and 15 with atopic dermatitis (AD). At week 8, IGA PN-A scores decreased from 3.27 ± 0.53 points at baseline to 1.31 ± 0.84 points ( t = 10.44, P < 0.001), with 16 (61.5%) patients achieving IGA PN-A 0/1; IGA PN-S scores decreased from 3.15 ± 0.46 points at baseline to 1.73 ± 0.78 points ( t = 10.33, P < 0.001), with 10 (38.5%) patients achieving IGA PN-S 0/1; pruritus NRS scores decreased from 5.00 (5.00, 6.00) points at baseline to 2.00 (1.00, 3.00) points ( Z = -3.82, P < 0.001), with 10 (38.5%) patients achieving a ≥ 4-point reduction in NRS scores. At week 40, 7 patients who continued treatment achieved complete remission. Univariate logistic regression showed that head/face involvement ( OR = 7.000, 95% CI: 1.200 - 40.829) and disease duration of < 1 year ( OR = 7.000, 95% CI: 1.200 - 40.829) were associated with better treatment response, while baseline IGA scores of 4 points predicted poorer outcomes ( OR = 0.114, 95% CI: 0.017 - 0.742). During treatment, conjunctivitis and local infection occurred in 2 cases without discontinuation, and no serious adverse events occurred in any of the cases. Conclusions:Dupilumab demonstrated rapid and sustained efficacy in pediatric PN with a favorable safety profile. Head/face involvement, shorter disease duration, and lower baseline severity were associated with better treatment response.