BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57％,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10％.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5％,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61％.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)％,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.

BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57％,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10％.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5％,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61％.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)％,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.

Objective To explore the mechanism of Pingchuanning Formula(PCN)for inhibiting airway inflammation in rats with asthmatic cold syndrome.Methods A total of 105 SD rats were randomized equally into 7 groups,including a control group,an asthmatic cold syndrome model group,3 PCN treatment groups at high,medium and low doses,a Guilong Kechuanning(GLCKN)treatment group,and a dexamethasone(DEX)treatment group.In all but the control rats,asthma cold syndrome models were established and daily gavage of saline,PCN,GLCKN or DEX was administered 29 days after the start of modeling.The changes in general condition,lung function and lung histopathology of the rats were observed,and inflammatory factors in the alveolar lavage fluid(BALF),oxidative stress,lung tissue ultrastructure,cytokine levels,and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed.Results The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass,food intake,and water intake,reduced FEV0.3,FVC,and FEV0.3/FVC,obvious inflammatory cell infiltration in the lung tissue,and increased alveolar inflammation score and counts of neutrophils,eosinophils,lymphocytes,macrophages,and leukocytes in the BALF.The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues,where the expressions of HMGB1,Beclin-1,ATG5,TNF-α,IL-6,IL-1β,and IL-13 and the LC3II/I ratio were increased,while the levels of Bcl-2 and IFN-γ were decreased.PCN treatment significantly improved these pathological changes in the rat models,and its therapeutic effect was better than that of GLKCN and similar to that of DEX.Conclusion PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy,thereby attenuating airway inflammatory damages.

BACKGROUND:Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar,but how it functions in hypertrophic scar is not clear. OBJECTIVE:To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.METHODS:Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected,and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis. RESULTS AND CONCLUSION:Compared with normal skin tissue and fibroblasts from normal skin tissue,the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P<0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing,chromosome synthesis and separation,and cell cycle. Among them,the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1,and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude,lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification,thus promoting the occurrence and development of hypertrophic scar.

BACKGROUND:At present,hydroxyapatite has been used more and more widely in the field of facial fillers due to its good biocompatibility and low immunity.The main sources are divided into natural extraction and artificial synthesis.However,there are few comparative studies on natural extraction and artificial synthesis of hydroxyapatite,especially the difference in stimulating collagen secretion between the two.OBJECTIVE:To investigate the physicochemical differences between naturally derived and commercially available synthetic calcium hydroxyapatite particles and promoting collagen secretion.METHODS:(1)Natural hydroxyapatite particles from pig bones and two kinds of commercially available synthetic hydroxyapatite particles(denoted as SYN1 and SYN2)were used to characterize the microstructure and surface element content of the three kinds of materials.(2)The three kinds of materials with different mass concentrations(1,5,and 10 mg/mL)were co-cultured with human skin fibroblasts.Cell proliferation was detected by CCK-8 assay.The three kinds of materials at 5 mg/mL were co-cultured with human skin fibroblasts.Cell adhesion was observed by CCK-8 assay and scanning electron microscopy.The expression of type Ⅰ collagen was detected by RT-PCR,ELISA,and western blot assay.(3)Twelve New Zealand rabbits were selected,of which six were subcutaneously injected with a mixture of natural hydroxyapatite and 2％sodium carboxymethylcellulose gel on the back.The remaining six rabbits were subcutaneously injected with a mixture of SYN2 and 2％sodium carboxymethylcellulose gel on the back.The samples were collected 1 and 3 months after injection and stained with Masson and Sirius red.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the crystal grains of natural hydroxyapatite particles were more regular and uniform,with holes evenly distributed between particles.The SYN1 grains were smaller and densely arranged,while the SYN2 grains were irregular.The median particle sizes of natural hydroxyapatite particles,SYN1,and SYN2 were 38,24,and 40 pm,respectively.Natural hydroxyapatite contained Mg and Zn,SYN1 did not contain Mg and Zn,and SYN2 did not contain Zn.(2)CCK-8 assay showed that 1 and 5 mg/mL of natural hydroxyapatite and SYN2 promoted the proliferation of human skin fibroblasts,while 5 and 10 mg/mL of SYN1 inhibited the proliferation of human skin fibroblasts.The number of cells adhered to the surface of natural hydroxyapatite particles was more than that of SYN1 and SYN2,and the cells on the surface of natural hydroxyapatite particles spread well,with visible filopodia.RT-PCR,ELISA,and western blot assay results showed that the expression of type Ⅰ collagen in the natural hydroxyapatite particle group was higher than that in the SYN1 group and the SYN2 group.(3)The results of Masson and Sirius red staining showed that the amount of type Ⅰ collagen in the subcutaneous tissue of the natural hydroxyapatite particle group was greater than that of the SYN2 group 1 and 3 months after injection.(4)The results show that compared with synthetic hydroxyapatite particles,natural hydroxyapatite particles have a richer distribution of trace elements and can better promote fibroblast adhesion,proliferation and collagen regeneration.

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.

Objective:To construct a volume management program for peritoneal dialysis patients in the peridialysis period.Methods:The intervention map was used as a guiding framework to build a first draft of a volume management program for peritoneal dialysis patients during the peridialysis period based on semi-structured interviews and a literature review in conjunction with a health belief model. Between December 2023 and February 2024, the first draft of the volume management program was revised by two rounds of expert consultation to produce a final program.Results:A total of 15 peritoneal dialysis medical and nursing experts were invited to complete two rounds of Delphi expert consultation. In the two rounds of expert consultation, 15 questionnaires were issued, and 15 valid questionnaires were recovered; the effective recovery rate was 100.00%, and the expert authority coefficient was both 0.903. The final constructed volume management program for peritoneal dialysis patients during the peridialysis period consisted of four first-level items (knowledge training, volume management plan development, behavioral assessment, and belief support), 10 second-level items, and 30 third-level items.Conclusions:The volume management program for peritoneal dialysis patients in the peridialysis period constructed in this study is scientific and can provide a reference for healthcare professionals.

Objective:To explore the distribution characteristics of HBsAg levels in treatment-na?ve and treatment-experienced patients with chronic hepatitis B (CHB) in China.Methods:Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-na?ve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean± SD, and M( Q1, Q3). Results:A total of 13 505 treatment-na?ve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-na?ve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-na?ve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially.Conclusions:The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-na?ve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

BACKGROUND:At present,hydroxyapatite has been used more and more widely in the field of facial fillers due to its good biocompatibility and low immunity.The main sources are divided into natural extraction and artificial synthesis.However,there are few comparative studies on natural extraction and artificial synthesis of hydroxyapatite,especially the difference in stimulating collagen secretion between the two.OBJECTIVE:To investigate the physicochemical differences between naturally derived and commercially available synthetic calcium hydroxyapatite particles and promoting collagen secretion.METHODS:(1)Natural hydroxyapatite particles from pig bones and two kinds of commercially available synthetic hydroxyapatite particles(denoted as SYN1 and SYN2)were used to characterize the microstructure and surface element content of the three kinds of materials.(2)The three kinds of materials with different mass concentrations(1,5,and 10 mg/mL)were co-cultured with human skin fibroblasts.Cell proliferation was detected by CCK-8 assay.The three kinds of materials at 5 mg/mL were co-cultured with human skin fibroblasts.Cell adhesion was observed by CCK-8 assay and scanning electron microscopy.The expression of type Ⅰ collagen was detected by RT-PCR,ELISA,and western blot assay.(3)Twelve New Zealand rabbits were selected,of which six were subcutaneously injected with a mixture of natural hydroxyapatite and 2％sodium carboxymethylcellulose gel on the back.The remaining six rabbits were subcutaneously injected with a mixture of SYN2 and 2％sodium carboxymethylcellulose gel on the back.The samples were collected 1 and 3 months after injection and stained with Masson and Sirius red.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the crystal grains of natural hydroxyapatite particles were more regular and uniform,with holes evenly distributed between particles.The SYN1 grains were smaller and densely arranged,while the SYN2 grains were irregular.The median particle sizes of natural hydroxyapatite particles,SYN1,and SYN2 were 38,24,and 40 pm,respectively.Natural hydroxyapatite contained Mg and Zn,SYN1 did not contain Mg and Zn,and SYN2 did not contain Zn.(2)CCK-8 assay showed that 1 and 5 mg/mL of natural hydroxyapatite and SYN2 promoted the proliferation of human skin fibroblasts,while 5 and 10 mg/mL of SYN1 inhibited the proliferation of human skin fibroblasts.The number of cells adhered to the surface of natural hydroxyapatite particles was more than that of SYN1 and SYN2,and the cells on the surface of natural hydroxyapatite particles spread well,with visible filopodia.RT-PCR,ELISA,and western blot assay results showed that the expression of type Ⅰ collagen in the natural hydroxyapatite particle group was higher than that in the SYN1 group and the SYN2 group.(3)The results of Masson and Sirius red staining showed that the amount of type Ⅰ collagen in the subcutaneous tissue of the natural hydroxyapatite particle group was greater than that of the SYN2 group 1 and 3 months after injection.(4)The results show that compared with synthetic hydroxyapatite particles,natural hydroxyapatite particles have a richer distribution of trace elements and can better promote fibroblast adhesion,proliferation and collagen regeneration.

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.