In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

Objective:To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin.Methods:ApoE -/-mice fed on Western diet were randomly assigned into the model group ( n=10) and the canagliflozin group ( n=10). C57BL/6J mice fed on normal diet were chosen as the control group ( n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results:HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE -/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE -/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues ( P<0.05). Conclusion:Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.

Objective:To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF).Methods:Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg -1·d -1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg -1·day -1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10 th week of the experiment, and echocardiography was performed at the 12 th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results:After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P<0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12 th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group ( P<0.05). The blood pressure of 6 th week and 12 th week, heart weight and left ventricular corrected mass of 12 th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12 th week was lower (all P<0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P<0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P<0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction ( P<0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe 2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P<0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P<0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P>0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups( P>0.05). Conclusion:Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

Objective: To investigate the protective effect of neurotrophic factor(MANF) derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway. Methods: 48 mice were randomly divided into 4 groups: control group, recombinant mouse MANF(rmMANF) group, cecal ligation and puncture(CLP) group and CLP+rmMANF group, with 12 mice in each group.The survival rate, sepsis score, anal temperature, blood biochemical indexes, pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS) related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group, LPS+rmMANF group, LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were analyzed. Results: Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased significantly(P<0.01),and the anal temperature and serum albumin(ALB) levels increased significantly(P<0.05).Compared with CLP group, the expression of MANF in CLP+rmMANF group increased significantly(P<0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and the percentage of TUNEL positive cells decreased significantly(P<0.05).In vitro, LPS stimulation down-regulated the expression of SIRT1 and AMPK in H9C2 cells, while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group, the expression of GRP78 and CHOP protein and the apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05). Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.

Objective To analyze the clinical characteristics and prognosis of patients with coronary slow flow(CSF)or no reflow(CNR)after emergency PCI.Methods A total of 443 elderly STEMI patients who underwent emergency PCI in Department of Cardiology of the First Affilia-ted Hospital of Tsinghua University from January 2017 to August 2023 were recruited,and ac-cording to thrombolysis in myocardial infarction(TIMI)flow grading after operation,they were divided into CSF/CNR group(TIMI grade≤2 flow,n=40)and normal flow(NCF)group(TIMI grade 3 flow,n=403).Logistic regression analysis was used to analyze the risk factors for CSF/CNR in STEMI patients after PCI.The prognosis was analyzed in the two groups.Results The CSF/CNR group had advanced age,longer durations from onset to admission and from onset to balloon opening,higher mortality rate,and larger proportions of chronic heart failure(CHF),type 2 diabetes mellitus(T2DM),pulse rate＞100 times/min,SBP＜100 mm Hg(1 mm Hg=0.133 kPa),Killip grade＞1,left anterior descending artery disease,LVEF＜50％,and using glycopro-tein Ⅱb/Ⅲa inhibitors and intraaortic balloon counterpulsation,but lower male ratio and DBP when compared with the control group(P＜0.05,P＜0.01).Multiple logistic regression analysis revealed that T2DM(OR=1.320,95％CI:0.618-2.123,P=0.046),mean SBP(OR=1.239,95％CI:0.752-1.525,P=0.04)and SBP＜100 mm Hg(OR=1.330,95％CI:0.836-1.675,P=0.013)were independent risk factors,while male was a protective factor(OR=-1.755,95％CI:-2.338--1.171,P=0.002)for CSF/CNR in STEMI patients after PCI.Conclusion T2DM and lower SBP are independent risk factors,while male is a protective factor for CSF/CNR in STEMI patients after emergency PCI.

Glomerular filtration rate(GFR)is a critical indicator of renal function assessment,which exhibits age-dependency in children and may differ from adults under various disease conditions.In recent years,there has been a growing focus on GFR among scholars,with an increasing number of clinical studies dedicated to refining and optimizing GFR estimation to span all pediatric age groups.However,the methods and assessment equations for estimating GFR may vary under different disease conditions,affecting the accuracy and applicability of assessments.This article reviews the peculiarities of renal function in children,explores GFR measurement methods,and evaluates the application of various GFR assessment equations in pediatric clinical practice,providing a reference for clinical assessment of renal function in children.

Aim To explore the protective effect of PPARδ agonist GW501516 on neuro-vascular unit(NVU)injury induced by high glucose in vitro and its mechanism.Methods SD rat hippocampal neurons(Neu),astrocytes(Ast)and brain microvascular en-dothelial cells(BMEC)were isolated,purified and cultured in vitro,and NVU co-culture system was estab-lished.NVU co-culture system cells were divided into the control group,high glucose group(HG group),HG+GW501516 low,medium and high concentration groups(25,50 and 100 nmol·L-1)and HG+GW501516(100 nmol·L-1)+ANA12(TrkB inhibi-tor,5 μmol·L-1)group.NUV barrier function was e-valuated by transendothelial resistance(TEER)test and leakage test;the proliferative activity of Neu cells in co-culture system was detected by CCK-8 assay;the levels of inflammatory cytokines TNF-α,IL-6 and IL-1β in cell supernatant were detected by ELISA;the levels of SOD,MDA and NO in Neu cells were detected by chemical method;the apoptosis level was detected by flow cytometry;the protein expression levels of PPARδ,Bax,Bcl-2,cleaved caspase-3,and BDNF/TrkB pathway-related proteins BDNF,p-TrkB,and TrkB in Neu cells were detected by Western blot.Re-sults Compared with the control group,the TEER val-ue decreased and leakage value increased in HG group;the proliferation activity of Neu cells decreased,the levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells increased,and the SOD lev-el decreased;Neu cell apoptosis rate and expression levels of Bax and Cleaved caspase-3 increased,while the expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB decreased(P＜0.05).Compared with the HG group,after treatment with different concentra-tions of GW501516,TEER value increased,leakage value decreased,proliferation activity of Neu cells in-creased,levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells decreased,and SOD level increased,and apoptosis rate of Neu cells and ex-pression levels of Bax and cleaved caspase-3 were de-creased,and expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB increased(P＜0.05)in a dose-dependent manner.However,ANA12 intervention re-versed the effect of GW501516 on NVU damage under high glucose conditions.Conclusion PPARδ agonist GW501516 improves in vitro NVU injury induced by high glucose by activating BDNF/TrkB signaling path-way.