Objective To explore the determinants of serum uric acid (UA) levels and the relationship between UA and cardiovascular disease in elderly patients.Methods A cross-sectional design was used.A total of 1 066 elderly patients were consecutively recruited in the study.Anthropometric measurement and lifestyle survey were performed,and serum UA,lipid profile,glucose,homocysteine (Hcy) and superoxide dismutase (SOD) were measured.The determinants of serum UA levels and correlation between UA and cardiovascular disease were analyzed by regression.Results The prevalence of hyperuricemia was 21.9％ (25.9％ in men and 18.7％ in women).Partial correlation analysis showed the level of serum UA was positively correlated with Hcy (r=0.163,P=0.000),body mass index (r=0.128,P=0.004) and triglyceride (r=0.133,P=0.003),and negatively correlated with HDL-C (r=-0.103,P=0.021).After adjustment for potential confounding factors,multivariate analysis showed eGFR (β =-2.044,t =-10.544,P =0.000),gender (β =42.065,t=4.700,P=0.000),Hcy (β=1.367,t=3.714,P=0.000),BMI (β=3.370,t=2.706,P=0.007),TG (β=14.120,t=2.589,P=0.010) and SOD (β=-0.636,t=-3.079,P=0.002) were independent determinants for UA levels in elderly patients.Logistic regression analysis indicated that mild elevation of UA levels was a risk factor of hypertension (OR=1.925,95％ CI=1.124-3.295) in women and OR=1.780 (95％ CI=1.010-3.136) in men].High UA levels increased the risk of coronary heart disease in women [OR=1.710 (95％ CI=1.157-2.526)],but decreased the risk of ischemic stroke in men [OR=0.524 (95％ CI=0.335-0.820)].Conclusions In elderly patients,serum UA levels were affected by renal function,gender,BMI and serum Hcy,TG and SOD.Mildly elevated UA levels increased the risk of hypertension.High UA levels increased the risk of coronary heart disease in women and decreased the risk of ischemic stroke in men.

Objective To investigate the effects of risk factors on non thyroidal Illness syndrome (NTIS) in elderly inpatients.Methods A total of 819 elderly inpatients who met inclusion criteria were consecutively recruited in thiscross-sectional study.Physicalmeasurements and mini nutritional assessment using the mini nutritional assessment-short form (MNA-SF) score were conducted.A serum levels of thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),brain natriuretic peptide (BNP) and C-reactive protein (CRP) were examined.Data were analyzed with multivariatelogistic regression.Results The significant differences were found between NTIS group (n=145) versus control group (n=674)inage (78.5±8.1) years vs.(75.1±8.6) years(t=5.422,P＜0.01),in body mass index (23.0 ±3.8) kg/m2 vs.(24.1±3.6) kg/m2,in MNA-SF score 11.2±2.3 vs.12.3± 1.8(t=-3.315,6.754,P＜0.01),in level of serum albumin (36.0±4.5) g/L vs.(38.4±3.6) g/L (t=-6.977,P＜0.01),in triglyceride level (1.3± 0.9) mmol/L vs.(1.5±1.0) mmol/L(t=-3.039,P＜0.01),inCRP (Z=-8.857,P＜0.01)),and in BNP (t=6.331,P＜0.01).Logistic regression analysis revealed that age＞ =80 years (OR=2.433,95％CI:1.357 4.361),malnutrition (OR=1.946,95％CI:1.261-3.001),renal insufficiency (eG FR＜60 ml/min,OR =2.131,95％ CI:1.367-3.322),and high level of CRP (10 mg/L and 50 mg/L:OR=3.446,95％CI:2.117-5.611;over 50 mg/L:OR =10.029,95％CI:4.693-21.432,all P＜0.01)) were risk factors for NTIS.Conclusions Non-thyroidal illness syndrome in elderly inpatients is correlated with advanced age,renal insufficiency,malnutrition and stress,which are the independent risk factors.

Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
Antineoplastic Agents ; therapeutic use ; CCAAT-Enhancer-Binding Protein-beta ; metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; methods ; trends ; NF-kappa B ; metabolism ; Neoplasms ; drug therapy ; metabolism ; Precision Medicine ; methods ; trends ; Signal Transduction ; drug effects ; Tumor Microenvironment ; drug effects

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

In this research, we studied the formation of Drosophila melanogaster FADD (Fas-associated death domain-containing protein) amyloid fiber and its influence on signal transduction in IMD (Immune deficiency) signaling pathway to better understand the regulation mechanism of Drosophila innate immune signaling pathway, which will provide reference for the immune regulation in other species. First, we purified dFADD protein expressed in Escherichia coli and performed Sulfur flavin T binding and transmission electron microscopy to identify the dFADD amyloid fibers formed in vitro. Then we investigated the formation of dFADD polymers in S2 cells using SDD-AGE and confocal microscope. We also constructed dFADD mutants to find out which domain is essential to fiber formation and its effect on IMD signal transduction. Our results revealed that dFADD could be polymerized to form amyloid fiber polymers in vitro and inside the cells. Formation of fibers relies on DED (Death-effector domain) domain of dFADD, since DED domain-deleted mutant existed as a monomer. Dual luciferase reporter assay showed that intact DED domain was required for the induction of downstream antimicrobial peptides, indicating that fiber formation was the key to IMD signal transduction. Our study revealed the role of dFADD in mediating the cascade between IMD and Dredd in the IMD signaling pathway by forming amyloid fibers, suggesting an evolutionarily conserved regulatory mechanism of innate immune signaling pathway.
Animals ; Drosophila Proteins ; biosynthesis ; immunology ; Drosophila melanogaster ; immunology ; Fas-Associated Death Domain Protein ; biosynthesis ; immunology ; Immunity, Innate ; immunology ; Signal Transduction

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.

BACKGROUNDDrug-eluting stents (DES) with durable polymer have significantly reduced restenosis and target vessel revascularization compared with bare metal stents. Durable polymer has been linked with persistent inflammation of vessel wall and delayed endothelial healing that may increase the risk of late and very late stent thrombosis. This study sought to evaluate the efficacy and safety of HELIOS completed biodegradable polymer sirolimus-eluting stent (SES) in de novo coronary lesions.

METHODSTotally, 287 patients with one or two de novo coronary lesions (lesion length ≤ 38 mm and reference vessel diameter 2.5-4.0 mm) were enrolled in the HOPE study, a prospective, multicenter, randomized, non-inferiority trial. Patients were randomized to treatment either with HELIOS completed biodegradable polymer SES (n = 142) or PARTNER durable polymer SES (n = 145). The primary endpoint was angiographic in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint included stent thrombosis and major adverse cardiac events including cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR).

RESULTSThe 9-month in-stent LLL in the HELIOS group was similar to the PARTNER group, (0.16 ± 0.22) mm vs. (0.19 ± 0.30) mm (P = 0.28). The difference and 95% confidence interval were -0.03 (-0.09, 0.04), and the P value for non-inferiority <0.01. Major adverse cardiovascular event (MACE) occurred in 7.9% vs. 8.2%, MI in 2.4% vs. 3.0%, TLR in 5.5% vs. 3.0%, and stent thrombosis in 0 vs. 1.5%; and events were comparable between the HELIOS group and PARTNER group at three-year follow-up (all P > 0.05). The three-year cardiac death was lower in the HELIOS group, but with no significant difference, 0 vs. 3.0% (P = 0.12).

CONCLUSIONSIn the HOPE trial, the novel completed biodegradable polymer SES HELIOS was non-inferior to the durable polymer SES PARTNER with respect to nine-month in-stent LLL in de novo coronary lesions. The incidence of other clinical endpoints was low for both of the stents in three-year follow-up.

Adult ; Aged ; Angiography ; Coronary Artery Disease ; surgery ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Humans ; Middle Aged ; Percutaneous Coronary Intervention ; Polymers ; chemistry ; therapeutic use ; Sirolimus ; therapeutic use ; Titanium ; chemistry ; Treatment Outcome ; Young Adult