AIM To investigate the flavor technology for Jiannaoning Mixture based on electronic tongue combined with preference index.METHODS Artificial sensory evaluation method was employed to screen the type of flavor agents,electronic tongue was applied to screening the consumption of flavor agents,and double-bottle preference test was adopted in the analysis of effects of rat gender and body weight on taste sensitivity,after which acceleration test was conducted.RESULTS Sucrose,stevioside and xylitol were taken as flavor agents,whose optimal consumptions were 15%,0.08%and 15%,respectively.Male rats demonstrated stable taste perception with the body weights of 220-280 g,and 0.08%stevioside displayed the best flavoring effect.After placed under accelerated condition for 3 months,the preparation exhibited stable appearance,pH value and contents of lobetyolin,salvianolic acid B,schizandrin,ruscogenin.CONCLUSION This stable and reliable method can provide reference for improving the terrible tastes of Jiannaoning Mixture and other oral liquid preparations of traditional Chinese medicines.

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Objective To investigate the impact of lncRNA DSCAM-AS1 on the malignant biological behaviors of thyroid cancer(TC)cells by regulating the miR-150-5p/BRAF axis.Methods The expression of DSCAM-AS1 in TC cells was detected by qRT-PCR,and the best intervention cell line was screened.;the relationship between DSCAM-AS1,BRAF and miR-150-5p targeting regulation was verified by FISH,pull down and double Luciferase reporter gene experiment;The proliferation,migration and invasion of SW579 cells were detected;Western blot was applied to detect the expression of BRAF,E-Cadherin,and vimentin proteins;the tumor formation experiment in mice was applied to verify the effect of DSCAM-AS1 on TC tumor growth.Results DSCAM-AS1 was highly expressed in TC tissue and cells(P<0.05);There is a targeted regulation relationship between DSCAM-AS1,BRAF and miR-150-5p;inhibition of DSCAM-AS1 expression or overexpression of miR-150-5p obviously inhibited the proliferation,migration,invasion,and EMT of SW579 cells(P<0.05);Inhibition of miR-150-5p expression or overexpression of BRAF reversed the inhibitory effect of inhibition of DSCAM-AS1 expression or overexpression of miR-150-5p on the malignant behavior of SW579 cells(P<0.05);in vivo experiments showed that inhibiting the expression of DSCAM-AS1 obviously inhibited the growth of transplanted tumors in mice(P<0.05).Conclusion DSCAM-AS1 is up-regulated in TC cells,inhibiting the expression of LncRNA DSCAM-AS1 can inhibit the malignant progression of TC by regulating the miR-150-5p/BRAF signaling axis.

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

OBJECTIVE: To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins. METHODS: In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (β value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively. RESULTS: In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (P_FPG=2.42×10^-19, FDR_FPG<0.001; P_HbA1c=1.72×10^-19, FDR_HbA1c<0.001). CONCLUSION In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.
Adult ; Blood Glucose ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Fasting ; Female ; Glycated Hemoglobin A ; Humans ; Male ; Middle Aged ; Twins, Monozygotic

Objective: To study the causes and influencing factors of no seeking medical treatment among pneumoconiosis patients. Methods: Using stratified sampling method and typical survey method, we carried out the questionnaire survey in nine provinces in China including the east, the medium and the western region using a questionnaire on the seeking medical behavior pf pneumoconiosis patients and the influencing factors. The subjects include occupational pneumoconiosis cases and clinically diagnosed cases and the response rate is 94.3 percent. The data was entered twice with epidate3.1 and error detection and statistical analysis was completed with SPSS 20.0. Chi-square test was used for univariate analysis, and multivariate logistic regression was used for multivariate analysis. Results: One thousand and thirty-seven subjects were investigated with average age 55.9±11.2 years. Seventy percent of them were silicosis and 21.9 percent were coal worker’s pneumoconiosis with 67.5 percent of them residing permanently in the countryside, and 37.9 percent of their education background were primary school culture and 33.1 percent of them had junior high school culture. Thirty two point six percent of respondents had no personal income with a median monthly income of 1 200 yuan. Four hundred and thirty four of subjects hadn't seek medical treatment since they got the pneumoconiosis accounting for 41.9 percent with three hundred and thirty seven of them hospitalized directly. The reasons of no seeking medical treatment for the respondents mainly include the self-induction symptoms lighter, the high cost of treatment and cannot claiming the payment of the medical expenses, buying drugs in drugstore, thinking that no medicine can cure pneumoconiosis or no effect, complex procedures, too far away from medical institutions, no unaccompanied, needing a long time or no time, communication disorders, etc. accounting for 44.4 percent, 24.6 percent, 10.9 percent, 9.1 percent, 6.9 percent, 4.4percent, 3.2 percent, 2.9 percent, 1.9 percent, 1.5 percent, respectively. The results of multivariate analysis showed the main characteristics of subjects with restrictions to the outpatient health service utilization are as follows: demographic sociological indicators such as registered permanent residence area is western (OR_western=2.18, 95%CI:1.38-3.43) , more than seventy five years old (OR_{over 75}=6.82, 95%CI:2.04-22.9) , unemployment, temporary or permanent employment (OR _unemployment=1.90, 95%CI:1.17-3.08; OR_{temporary employment}=3.11, 95%CI:1.57-6.14; OR_{permanent employment}=2.10, 95%CI:1.18-3.74) , self-rated health score of 50 or above (OR_{self-rated-70}=2.04, 95%CI:1.18-3.51; OR_{self-rated-90}=3.00, 95%CI:1.97-5.37; OR_{self-rated 90}=2.95, 95%CI:1.74-8.07) ; with increase to the outpatient health service utilization are breath with difficulty (OR=0.57, 95%CI:0.41-0.78) , emphysema (OR=0.48, 95%CI:0.26-0.90) , hospitalized with pneumo-coniosis (OR=0.12, 95%CI:0.07-0.20) . Conclusion Pneumoconiosis patients no covered by injury insurance should be orderly included in the basic medical security system, and be given the medical treatment actively; It should be strengthened the health management for the pneumoconiosis patients and correctly guided the utilization of medical services.

Objective: To investigate the situation where pneumoconiosis patients who should be in hospital are not hospitalized, to analyze the main reasons and influencing factors for their restricted use of hospitalization medical services, and to provide a reference for relevant policy making. Methods: Subjects were sampled in nine provinces, including Zhejiang, Jiangsu, Shandong, and Hebei, using a method that combined stratified sampling and typical sampling, from March 2017 to January 2018. These subjects were patients occupationally diagnosed with pneumoconiosis and patients clinically diagnosed with pneumoconiosis. The questionnaire The health seeking behaviors of pneumoconiosis patients and their influencing factors was used as the survey tool to investigate their health seeking behaviors such as going to the outpatient clinic and being hospitalized. Andersen's Behavioral Model of Health Services Use was used as the analysis model; The χ2 test was used for univariate analysis, and the multivariate logistic regression model was used for multivariate analysis. Results: A total of 1 037 patients with pneumoconiosis were surveyed, with a mean age of 55.9±11.2 years and 67.5% (700/1 037) living in rural areas for a long time. Occupational injury insurance and medical insurance for urban and rural residents were the main insurances used, accounting for 40.9% (424/1 037) and 59.4% (616/1 037) of the cases, respectively. A total of 177 (17.1%) patients were once advised by the doctors to be hospitalized because of pneumoconiosis, while they did not. The proportion of patients who should be in hospital but did not do so among rural patients was significantly higher than that in urban patients (20.1% (141/700) vs 10.7% (36/337) , P<0.05) . Financial difficulties (12.0%, 124/1 037) and self-rated mild symptoms (3.2%, 33/1 037) were the main reasons for not being hospitalized. Model analysis showed that the propensity factor, ability factor, health needs, health seeking behaviors, and self-rated health factor in the Anderson model were all statistically significant (P<0.05) . The main features of high proportion of patients who should be in hospital but did not do so were as follows: personal monthly income below 1 000 RMB (odds ratio[OR]of no income=2.92, 95% confidence interval[CI]: 1.14-7.48; OR of less than 1 000 RMB=3.55, 95%CI: 1.35-9.35) , no occupational injury insurance (OR=2.05, 95%CI: 1.16-3.43) , and concurrent emphysema (OR= 1.98, 95%CI: 1.12-3.50) . Conclusion Low income, no occupational injury insurance, and concurrent emphy-sema are the main constraining factors for hospitalization services use in pneumoconiosis patients.

Objective To investigate the uptake mechanism of HepG2.2.15 cells to the nanoparticles co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). Methods The nanoparticles were prepared by using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol. The uptake mechanism of HepG2.2.15 cells to SH-NPs was studied by fluorescence microscopy and flow cytometry using fluoresceineisothiocyanate (FITC) as a fluorescent marker. Results With colchicine as the inhibitor, the incubation time ranged from 0.5 to 24 h, the percentage of positive cells increased from 1.9% to 56.4%; When the drug concentration was 125, 250 μg/mL and 500 μg/mL, the positive cell percentages were 4.9%, 3.4% and 3.9%. With chloroquine as the inhibitor; the incubation time ranged from 0.5 to 24 h, the percentage of positive cells increased from 7.4% to 55.4%; When the drug concentration was 125, 250 and 500 μg/mL, the percentage of positive cells was 19.5%, 22.5% and 27.6%. Conclusion Colchicine and chloroquine have an inhibitory effect on HepG2.2.15 cells uptake, and the uptake of SH-NPs in HepG2.2.15 cells was positively correlated with drug concentration and incubation time. It can be concluded that the uptake mechanism of HepG2.2.15 cells to SH-NPs was nonspecific adsorption endocytosis.

Objective: To assess the feasibility of HEAD-US scale in the clinical application of hemophilic arthropathy (HA) and propose an optimized ultrasound scoring system. Methods: From July 2015 to August 2017, 1 035 joints ultrasonographic examinations were performed in 91 patients. Melchiorre, HEAD-US (Hemophilic Early Arthropathy Detection with UltraSound) and HEAD-US-C (HEAD-US in China) scale scores were used respectively to analyze the results. The correlations between three ultrasound scales and Hemophilia Joint Health Scores (HJHS) were evaluated. The sensitivity differences of the above Ultrasonic scoring systems in evaluation of HA were compared. Results: All the 91 patients were male, with median age of 16 (4-55) years old, including 86 cases of hemophilia A and 5 cases hemophilia B. The median (P₂₅, P₇₅) of Melchiorre, HEAD-US and HEAD-US-C scores of 1 035 joints were 2(0,6), 1(0,5) and 2(0,6), respectively, and the correlation coefficients compared with HJHS was 0.747, 0.762 and 0.765 respectively, with statistical significance (P<0.001). The positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 63.0% (95%CI 59.7%-65.9%), 59.5% (95%CI 56.5%-62.4%) and 56.6% (95%CI 53.6%-59.6%) respectively, and the difference was statistically significant (P<0.001). Even for 336 cases of asymptomatic joints, the positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 25.0% (95%CI 20.6%-29.6%), 17.0% (95%CI 12.6%-21.1%) and 11.9% (95%CI 8.4%-15.7%) respectively, and the difference was statistically significant (P<0.001). There were significant changes (P<0.05) in the ultrasonographic score of HA before and after onset of hemorrhage in 107 joints of 40 patients. The difference in variation amplitude of HEAD-US-C scores and HEAD-US scores before and after joint bleeding was statistically significant (P<0.001). Conclusion: Compared with Melchiorre, there were similar good correlations between HEAD-US, HEAD-US-C and HJHS. HEAD-US ultrasound scoring system is quick, convenient and simple to use. The optimized HEAD-US-C scale score is more sensitive than HEAD-US, especially for patients with HA who have subclinical state, which make up for insufficiency of sensitivity in HEAD-US scoring system.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Hemarthrosis ; Hemophilia A ; Hemophilia B ; Humans ; Male ; Middle Aged ; Ultrasonography ; Young Adult