Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P＜0.01),increased MDA level(P＜0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P＜0.05),decreased MDA level(P＜0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P＜0.05,P＜0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P＜0.05,P＜0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Objective To analyze the basic conditions and pathological characteristics of the samples in the Human Brain Bank of Hebei Medical University,which were pathologically diagnosed as cerebral amyloid angiopathy,and to provide reference for the research of related diseases.Methods The basic data of gender,age,apolipoprotein E genotype,pathological classification of cerebral amyloid angiopathy,Alzheimer's disease-related pathological change score,comorbidities and other pathological information were analyzed.Results Up to October 2024,twenty samples were confirmed by pathological diagnosis,with a male to female ratio of 3:1 and an average age of(80.90±8.08)years.Involve three kinds of apolipoprotein E subtype,5 kinds of genotypes(ε2/ε3 xε2/ε4、ε3/ε3 xε3/ε4、ε4/ε4);There were 2 pathologic types,including 6 cases of type 1 and 14 cases of type 2.The pathological grade included 3 grades.The severity grade and subtype classification of cerebral amyloid vascular disease were correlated with the degree of pathological changes of Alzheimer's disease.Cerebral amyloid angiopathy samples could coexist with other degenerative diseases with high comorbidity.Conclusion The incidence of cerebral amyloid angiopathy is higher in the aged samples collected based on Brain Bank,which coexists with conditions such as Alzheimer's disease and microbleeds,etc.It provides more detailed pathological diagnosis basis for further scientific research sharing of samples.

Objective To observe the value of quantitative CT(QCT)analysis of human body components for predicting microvascular invasion(MVI)status of hepatocellular carcinoma(HCC).Methods Totally 60 HCC patients were retrospectively enrolled and divided into positive group(n=15)and negative group(n=45)based on postoperative pathology findings of MVI or not.Human body composition parameters,including bone mineral density(BMD),subcutaneous fat area(SFA),visceral fat area(VFA),total fat area(TFA)and subcutaneous/visceral fat area ratio(SVR),as well as muscle fat area(MFA),muscle area(MA)and muscle fat infiltration(MFI)of posterior vertebral muscle group based on QCT were compared between groups,and the efficacy of the above parameters for predicting MVI status of HCC was observed.Results SFA,TFA,MFA and MFI were all higher,while MA was lower in positive group than those in negative group(all P＜0.05).The area under the curve(AUC)of SFA,VFA,TFA,MA,MFA and MFI for predicting MVI status of HCC ranged from 0.673 to 0.790(all P＜0.05).TFA and M FI were both independent risk factors of HCC MVI(both P＜0.05),with AUC of 0.790 and 0.759,respectively.Conclusion QCT analysis of human body components was helpful to predicting MVI status of HCC.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.