OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

Objective: To analyze the time-related factors influencing daily blood donation attendance at fixed donation sites in Nanjing and the heterogeneity among sites, and to provide evidence for optimizing site layout and operational management. Methods: Based on daily attendance data from 17 fixed donation sites in Nanjing for the full year of 2025, matched with contemporaneous meteorological and air quality data, a two-stage negative binomial generalized linear mixed model (NB-GLMM) was constructed. In the second stage, site-level static characteristics (number of scenic spots, daily operating hours, number of shopping malls, public transport stops, hospitals, universities, and residential buildings) were additionally incorporated. Model comparison was performed using Akaike information criterion (AIC). Significance of random effects was tested by likelihood ratio test, and site-specific random effects were extracted using empirical Bayes estimation. Robustness of the results was verified through residual diagnostics and multiple sensitivity analyses. Results: The first-stage model showed that rainfall was associated with lower attendance (IRR=0.943, P<0.001); holidays were associated with higher attendance (IRR=1.162, P<0.001); Saturdays and Sundays showed higher attendance than Mondays, with the strongest association on Sundays (IRR=1.195, P<0.001). Temperature exhibited a non-linear relationship (linear term P=0.051, quadratic term P=0.036). The joint results of the linear and quadratic terms for temperature suggested a nonlinear relationship between attendance and temperature. After introducing static characteristics in the second stage, the number of scenic spots (IRR=1.372, P=0.008) and daily operating hours (IRR=1.823, P<0.001) were found to be positively associated with attendance, while the numbers of shopping malls, public transport stops, hospitals, universities, and residential buildings showed no significant effects. Conclusion: Daily blood donation attendance at fixed sites in Nanjing is influenced by multiple factors including weather, day of the week, holidays, and site surroundings. Substantial heterogeneity exists among different sites; extended operating hours and more nearby scenic spots are associated with increased attendance.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16％.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P＜0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P＜0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.

Objective:To investigate the effect of uridine diphosphate ceramide galactosyltransferase 8(UGT8)on colorectal cancer(CRC)cell growth and migration,elucidate an underlying mechanism,and assess the potential regulatory role of SRY-box transcription factor 9(SOX9)on UGT8.Methods:UGT8 and SOX9 mRNA expression levels in CRC tissues,and correlation between their expression levels,were analyzed using GEPIA2,UALCAN,and TIMER 2.0 online databases.UGT8 and SOX9 protein expression in CRC and adjacent tissues was detec-ted using immunohistochemistry,and relationships between their expression and clinicopathological characteristics were analyzed.Impact of UGT8 knockdown on CRC cell proliferation was assessed using a CCK-8 assay,and cell migration was evaluated using Transwell and wound healing assays.Western blot was performed to detect expression of epithelial-mesenchymal transition(EMT)markers(E-cadherin and ZEB1).RT-qPCR and Western blot were used to measure UGT8 mRNA and protein expression levels after SOX9 knockdown.The JASPAR online database was used to assess SOX9 potential for binding to the UGT8 promoter.Results:Bioinformatics analyses revealed significantly higher mRNA expression levels of both UGT8 and SOX9 in CRC tissues than in normal tissues.Positive correlation was observed between expres-sion levels.Immunohistochemistry results showed that tumor UGT8 and SOX9 protein levels were significantly higher than those in adjacent tissues.UGT8 protein level was found to correlates with N stage,and SOX9 protein level correlated with T stage.A positive correlation was observed between UGT8 and SOX9 expression levels.Following UGT8 knockdown,cell proliferation capacity was attenuated and cell migra-tion ability was reduced.E-cadherin expression concurrently increased and ZEB1 expression decreased.RT-qPCR and Western blot results showed that SOX9 knockdown significantly reduced UGT8 mRNA and protein levels.The JASPER website predicts that SOX9 will bind to the UGT8 promoter.Conclusions:UGT8 and SOX9 are highly expressed in CRC tissues,and their expression levels correlate with clinicopatholo-gical features.UGT8 and SOX9 expression levels display significant positive correlation.Mechanistically,UGT8 promotes CRC cell prolifera-tion and migration by facilitating epithelial-mesenchymal transition(EMT).SOX9 enhances UGT8 mRNA and protein expression and may bind to the UGT8 promoter region.

Objective To screen specific antibodies to Helicobacter pylori(H.pylori)in serum,and establish antibody panels and discrimination models for different infection status,which are non-invasive and suitable for gastric cancer screening in Chinese population.Methods A total of 300 subjects with different H.pylori statuses were enrolled depending on an endoscopy screening cohort in a high-risk area of gastric cancer,including current,past,and negative infections.The recomLine Helicobacter IgG 2.0 immunoblotting assay was used to analyze and screen 10 H.pylori specific antibodies in serum samples.Results A total of nine antibody reactivity against CagA,VacA,GroEL,FliD,HpaA,gGT,HtrA,NapA,and CtkA showed significant differences among different H.pylori infection status groups(all P＜0.05).A panel comprising the nine antibodies distinguished exposure subjects to H.pylori(current and past infections)from negatives,with an area under the curve(AUC)of 0.935(95%CI:0.907-0.963).The combination of four antibodies(CagA,GroEL,FliD,and gGT)may help to discriminate current and past infection subjects,with an AUC of 0.927(95%CI:0.891-0.964).Conclusion The antibody panels and discriminant models for H.pylori infection status established in the present study may provide a potential and non-invasive screening method for the development of precise gastric cancer prevention strategies.

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Objective To construct a nursing registry platform for percutaneous coronary intervention(PCI)to provide data support for subsequent real-world research on PCI nursing.Methods From April to December 2023,we established a variable list and data dictionary based on literature review and expert discussion,and constructed a web-based PCI nursing registry platform based on registry-related standards.Results A total of 191 variables were screened in this study,and a corresponding data dictionary was developed for each variable according to the variable name,variable code,variable definition,variable type,variable value range,data source and data collection node.Three levels of account privileges has been set up in the platform,which can realize different data management privileges,and the data can be saved only after filling in and reviewing at each level.The platform is also equipped with automatic data checking function,which reduces data filling errors and improves data quality.Conclusion The constructed PCI nursing registration platform has strong scientific and professional characteristics,and can provide data support for subsequent research,and the content and functions of the platform can be further optimized in the future.