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 examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

Objective To investigate the prevalence and the risk factors of heart disease(HD)in adults aged ≥80 years old in China based on the data from the 8th round of the Chinese Longitudinal Healthy Longevity Survey(CLHLS).Methods A total of 7 675 adults aged ≥80 years old were enrolled from the 8th round of CLHLS dataset.Chi-square tests were employed to examine associations between cardiovascular disease and demographic characteristics,socioeconomic status,social support,lifestyle factors,and health indicators.Logistic regression models were developed to analyze significant predictors of heart disease in the elderly.Results The prevalence of heart disease was 16％(n=1 228)in 7 675 elderly people.Aged 90-99 years old(odds ratio[OR]=0.816),≥100 years old(OR=0.641),female(OR=0.833),and low body mass index(BMI)(＜18.5 kg/m2,OR=0.778)were the protective factors for cardiovascular disease in the elderly;and high BMI(24.0 to 27.9 kg/m2,OR=1.209),rural residence(OR=2.384),health examination(OR=1.164),dysfunction of daily living activities(OR=1.401),hypertension(OR=2.143),diabetes mellitus(OR=1.719),and history of cerebrovascular accident(OR=2.080)were risk factors.Conclusion Male,overweight,rural residence,health examination,dysfunction of daily living activities,hypertension,diabetes mellitus,and a history of cerebrovascular accident are the risk factors for heart disease in the elderly.

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 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 investigate the effects of Zhibai Dihuang Pills on neurons of cognitive dysfunction in D-galactose (D-gal) model mice.Methods:Totally 60 male mice were divided into four groups using a random number table method: control group, model group, donepezil group, and Zhibai Dihuang Pills group, with 15 mice in each group. Except for the control group, the other groups were subcutaneously injected with D-galactose solution at a dosage of 125 mg/kg once a day for 8 weeks to prepare the aging model. Mice in the donepezil group were intragastrically administered donepezil solution at a dosage of 0.65 mg/kg, and those in the Zhibai Dihuang Pills group were intragastrically administered Zhibai Dihuang Pills solution at a dosage of 1.56 g/kg. The control group was intragastrically administered an equal volume of physiological saline once a day for 8 weeks. The object recognition test and Morris Water Maze were used to assess object recognition memory and spatial learning memory abilities of mice in each group, respectively. Hematoxylin-Eosin (HE) staining and Nissl staining were employed to observe the morphology of neurons in the hippocampal region; Golgi staining was used to observe neuronal dendritic spines; Western Blot was used to detect the protein expression levels of PI3K, p-Akt/Akt, glycogen synthase kinase 3β (GSK3β), postsynaptic density protein-95 (PSD-95), and synaptophysin (SYP) in the hippocampus region; RT-qPCR was performed to detect mRNA expression of PI3K, Akt and GSK3β in the hippocampus region.Results:Compared with the model group, the recognition index in both the donepezil group and the Zhibai Dihuang Pills group increased ( P<0.05), the escape latency was shortened ( P<0.05), the platform crossings times and the target quadrant dwell time increased ( P<0.05), the number of nerve cells in the hippocampal region increased, arranged closely, the number of Nissl bodies increased, the morphology returned to normal, and the density of dendritic spines increased; the protein expressions of PI3K, PSD-95, and SYP in the hippocampal region and the ratio of p-Akt/Akt increased ( P<0.01), the mRNA level of PI3K increased ( P<0.01 or P<0.05), and the protein and mRNA levels of GSK3β decreased ( P<0.01 or P<0.05). Conclusion:Zhibai Dihuang Pills can improve the learning and memory ability and rescue neuronal damage in D-gal model mice, and the mechanism may be related to the activation of PI3K/Akt pathway and the restoration of synaptic connections.

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.

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 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.