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.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Traditional Chinese medicine and Western medicine exhibit significant differences in their modes of thinking， yet this very distinction creates opportunities for their mutual learning and integration. TCM ethics are grounded in the robust theoretical and practical foundations of TCM. From the three-dimensional ethical perspective of cognition， decision-making， and treatment， it demonstrates prominent characteristics in the cognitive regulation of “taking images to operate numbers，” the decision-making principle of “treatment based on syndrome differentiation，” and the therapeutic criteria of “harmony between humanity and nature.” TCM and Western medicine possess distinct features in image-based thinking and reductionism， dynamic nonlinearity and static linearity， as well as holism and antagonism， influencing how they address doctor-society， doctor-doctor， and doctor-patient relationships. Furthermore， the integration of TCM and Western medicine can foster mutual learning and allow them to complement each other’s strengths. Against the backdrop of growing emphasis on TCM modernization and the steady advancement of the Healthy China initiative， enhancing the healthcare system’s adaptability to diverse health demands is crucial. Efforts should be made to promote proper subject-object regulations in the doctor-society relationship， a harmonious yet competitive plurality in the doctor-doctor relationship， and harmonious coexistence in the doctor-patient relationship. It is also essential to uphold the parallel progression of ethical reflection and practical exploration， thereby providing ethical support for the further development of integrated Chinese and Western medicine.

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 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.

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.