INTRODUCTION: Comparison of patient health-related quality of life (HRQOL) scores to a reference group is needed to quantify the HRQOL impact of disease or treatment. This study aimed to establish population norms for 2 HRQOL questionnaires-EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Question-naire 30 (EORTC QLQ-C30) according to age, sex and ethnicity-and to explore relationships between the EQ-5D-5L, EORTC QLQ-C30 and sociodemographic characteristics. We used a representative sample of adult Singapore residents aged 21 years and above. METHOD: This study used data collected from a cross-sectional household survey in which 600 adult Singaporeans completed questions on sociodemo-graphic characteristics-the EQ-5D-5L and the EORTC QLQ-C30. Multiple linear regression analyses were conducted to explore associations between sociodemographic characteristics, the EQ-5D-5L scores and the EORTC QLQ-C30 scores. Regression-based population norms were computed for each subgroup using a post-stratification method. RESULTS: In multiple linear regression analysis, age was significantly associated with EQ-5D-5L index and visual analogue scale (VAS) scores, while no sociodemographic characteristics were significantly associated with EORTC QLQ-C30 summary scores. The normative EQ-5D-5L index and VAS scores decreased in adults aged 65 years and above, and EQ-5D-5L index scores were slightly lower in females than males and in non-Chinese than Chinese. The normative EORTC QLQ-C30 summary scores were slightly higher in Chinese than in the non-Chinese group and in the 45-64 age group than other age groups. CONCLUSION This study provides population norms for the EQ-5D-5L and EORTC QLQ-C30 for the general adult population in Singapore. Future studies of patient populations in Singapore using EQ-5D-5L or QLQ-C30 can use these normative data to interpret the HRQOL data collected.
Humans ; Quality of Life ; Singapore ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; Surveys and Questionnaires ; Young Adult ; Health Status ; Age Factors ; Linear Models ; Aged, 80 and over

Constructing an efficient and easy-to-operate multigene expression system is currently a crucial part of plant genetic engineering. In this study, a fragment carrying three independent gene expression cassettes and the expression unit of the gene-silencing suppressor protein(RNA silencing suppressor 19 kDa protein, P19) simultaneously was designed and constructed. This fragment was cloned into the commonly used plant expression vector pCAMBIA300, and the plasmid pC1300-TP2-P19 was obtained. Each gene expression cassette consists of different promoters, fusion tags, and terminators. The target gene can be flexibly inserted into the corresponding site through enzymatic digestion and ligation or recombination and fused with different protein tags, which provides great convenience for subsequent detection. The enhanced green fluorescent protein(eGFP) reporter gene was individually constructed into each expression cassette to verify the feasibility of this vector system. The results of tobacco transient expression and laser-confocal microscopy showed that each expression cassette presented independent and normal expression. Meanwhile, the three key enzyme genes in the betanin synthesis pathway, BvCYP76AD, BvDODA1, and DbDOPA5GT, were constructed into the three expression cassettes. The results of tobacco transient expression phenotype, protein immunoblotting(Western blot), and chemical detection of product demonstrated that the three exogenous genes were highly expressed, and the target compound betanin was successfully produced. The above results indicated that the constructed multigene expression system for plants in this study was efficient and reliable and can achieve the co-transformation of multiple plant genes. It can provide a reliable vector platform for the analysis of plant natural product synthesis pathways, functional verification, and plant metabolic engineering.
Nicotiana/metabolism* ; Genetic Vectors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Genetic Engineering/methods* ; Green Fluorescent Proteins/metabolism* ; Gene Expression

Objective To investigate the specific molecular mechanism through which microRNA-4488(miR-4488)regulates the proliferation,migration and invasion capabilities of glioblastoma(GBM)by modula-ting the expression level of scratch family transcriptional repressor 1(SCRT1).Methods Quantitative real-time PCR(qPCR)was performed to measure the expression levels of miR-4488 and SCRT1 in astrocyte SVG cells and GBM U87MG cells.Transient transfection was used to introduce miR-4488 mimic nc(mimic control group),miR-4488 mimic(mimic group),miR-4488 inhibitor nc(inhibitor control group),and miR-4488 inhib-itor(inhibitor group)into U87MG cells,which were then divided into four groups accordingly.Lentiviral transfection was used to establish U87MG cell lines transfected with SCRT1 empty vector(control group)and SCRT1 overexpression plasmid(overexpression group).Bioinformatics analysis was performed to identify and validate the binding site sequence between miR-4488 and SCRT1,and the dual-luciferase reporter gene as-say was conducted to verify their targeting relationship.The EdU assay was employed to assess cell prolifera-tion capacity,while the Transwell assay was used to analyze differences in migratory and invasive capacities a-mong groups.Results Compared with SVG cells,miR-4488 expression was upregulated(P＜0.001)and SCRT1 expression was downregulated in U87MG cells(P＜0.001).After transient transfection with miR-4488 mimic,the expression of SCRT1 in the mimic group decreased compared to the mimic control group,with no significant change in proliferative capacity(P＞0.05),but enhanced migration and invasion abilities(P＜0.01 and P＜0.001,respectively).Conversely,after transfection with miR-4488 inhibitor,the expression of SCRT1 in the inhibitor group increased compared to the inhibitor control group,with no significant change in proliferative capacity(P＞0.05),but weakened migration and invasion abilities(P＜0.01 and P＜0.001,re-spectively).The dual-luciferase reporter gene assay confirmed that SCRT1 is a target of miR-4488 in U87MG cells.The SCRT1 overexpression group showed reduced migration and invasion abilities compared to the con-trol group(P＜0.01 and P＜0.001,respectively).Conclusion MiR-4488 can specifically regulate the expres-sion of SCRT1 to affect the migration and invasion characteristics of GBM.

Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To explore the mechanism of melatonin(Mel)alleviating cholestatic liver injury in a mouse cholestasis model induced by cholic acid(CA)feeding.Methods A total of 15 8-week-old male C57BL/6J mice were randomly divided into control group,1％CA group,and 1％CA+Mel group,with 5 animals in each group.The control group was fed with normal chow diet,and the other 2 groups were fed with a diet containing 1％CA for 14 d to construct a model of cholestasis,and intraperitoneal injection with 100 mg/kg Mel was given to the mice from the 1％CA+Mel group.Immunohistochemical assay of α-SMA was applied for the liver tissues in the 1％CA group and the 1％CA+Mel group.The mRNA expression levels of fibrosis-related indicators in mouse liver tissue were examined by RT-qPCR.Liquid chromatography tandem mass spectrometry(LC-MS/MS)and automated biochemical analyzer were used to detect the contents of bile acids in the liver tissues and the serum of mouse,respectively.Then real-time qPCR and Western blotting were applied to detect the expression of bile acid synthesis and liver detoxification enzymes related indicators at mRNA and protein levels,respectively,to further investigate the mechanism of bile acid metabolism.Results Compared with the 1％CA group,the mRNA levels of liver fibrosis indicators(such as Tgfβ1,Col Ⅰ a1,Col Ⅱa1 and α-SMA)were significantly reduced(P＜0.05),and activation of stellate cells was obviously weakened displayed by immunohistochemical staining in the 1％CA+Mel group.The 1％CA+Mel group had notably decreased contents of bile acids in the serum and liver tissues,especially taurocholic acid and reduced mRNA levels of cholesterol 7α-hydroxylase(Cyp7a1)and Cyp8b1,while enhanced mRNA levels of hepatic detoxification enzymes Cyp2b10 and udp-glucuronosyltransferase(Ugt1a1)as well as protein levels of Cyp2b10 and sulfotransferase family 2A member 1(Sult2a1/2)when compared with the 1％CA group(P＜0.05).Conclusion Mel exerts its therapeutic effect on cholestasis by decreasing bile acid synthesis and increasing hepatic detoxification enzymes.

By using paddy rice harvested between 2019 and 2023 as the research object,the volatile components of rice grains were detected by headspace solid-phase microextraction coupled with gas chromatography-triple quadrupole mass spectrometry.Qualitative analysis of the compounds was complemented by a standard mass spectrometry database and retention index,while a selected ion monitoring approach was established to quantify the contents of each component through the internal standard method.Multivariate statistical analyses including principal component analysis and orthogonal partial least squares discriminant analysis were employed to identify differential compounds related to freshness of the paddy rice.Subsequently,a classification model for identifying stored paddy rice based on volatile component analysis was developed.A total of 44 kinds of volatile compounds were identified across different harvest years,including aldehydes,alcohols,ketones,acids,esters,phenols and furans.The results of the multivariate statistical analysis revealed that the content-based orthogonal partial least squares discriminant analysis model could effectively distinguish 2023 harvested paddy rice from those harvested between 2019 and 2022 into two distinct categories.Notably,compounds such as hexanoic acid and nonanoic acid along with twelve others were identified as differential compounds based on variable improtance in projection(VIP)values exceeding 1 and p values less than 0.05.The classification model established through volatile component analysis was expected to provide a theoretical foundation for assessing the freshness of stored paddy rice.

Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.

Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.

Objective:To explore the effect of partial splenectomy with minimally invasive surgical technique in treating splenic benign lesions.Methods:The clinical data of 19 patients, who underwent partial splenectomy with laparoscopic and robotic surgery for benign lesions of spleen, in Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2021 to January 2023 were retrospectively analyzed. There were 11 males and 8 females, with the age of (29.2±10.1) years old. Clinical data, such as gender, age, operating procedure, intraoperative blood loss, operation time, postoperative hospital stay and postoperative complications, were collected.Results:Nineteen patients successfully underwent partial splenectomy with minimally invasive surgery, including laparoscopic partial splenectomy (13 cases) and robotic partial splenectomy (6 cases). Irregular partial splenectomy was performed in 10 patients, and regular partial splenectomy in 9 patients. There was no conversion to open surgery. Operation time, intraoperative blood loss, postoperative hospital stay and time of postoperative drainage tube indwelling were 178(130, 200) min, 200(50, 300) ml, 6 (4, 7) d and 3(2, 5) d. Postoperative complications developed in 4 cases (21.1%, 4/19), including left pleural effusion (3 cases) and spleen remnant infarction (1 case).Conclusion:Partial splenectomy by minimally invasive surgery in treating splenic benign lesions is safe and feasible.