Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective:To investigate the feasibility of DNA tetrahedral framework (DNA-TH) as a carrier and adjuvant for mucosal vaccines, using streptavidin (SA) as a model antigen.Methods:DNA-TH was designed using software, integrating the adjuvant CpG sequence into its structure. After in vitro synthesis, it was conjugated with SA to form SA-DNA-TH nanoparticles. In vitro experiments: free SA and the two-dimensional structure SA-CpG (SA directly conjugated to CpG) were used as controls. The uptake efficiency of SA-DNA-TH by mouse primary macrophages and its ability to activate antigen-presenting cells (APCs) were evaluated. In vivo experiments: following submucosal oral injection, a mixture of free SA and free CpG (mixed group) was used as a control. The distribution of SA within mouse lymph nodes was observed using immunofluorescence staining. Levels of SA-specific antibodies (serum IgG, IgM; salivary sIgA) in serum and saliva were measured to assess humoral and mucosal immune responses.Results:Native polyacrylamide gel electrophoresis confirmed the successful synthesis of DNA-TH and SA-DNA-TH. In vitro experiments: SA-DNA-TH was rapidly taken up by primary macrophages. Its uptake rate (92.65%±4.43%) was significantly higher than that of the SA-CpG group (25.37%±3.56%) and the free SA group (1.80%±1.02%; both P<0.01). SA-DNA-TH also induced significantly stronger APC activation (OD value fold increase: 3.60±0.32) compared to the free SA group (1.13±0.10) and the SA-CpG group (1.21±0.02; both P<0.01). In vivo experiments: lymph node distribution analysis revealed overlapping signals of SA with subcapsular sinus macrophages (SCSMs) and dendritic cells (DCs) in the SA-DNA-TH group, whereas SA signals appeared dispersed and non-overlapping with APCs in the mixed group. Regarding immunogenicity, both serum anti-SA antibody (IgG+IgM) titers and salivary anti-SA sIgA antibody titers induced by SA-DNA-TH were significantly higher than those in the mixed group and the blank control group (both P<0.05). Conclusion:DNA-TH effectively delivers the model antigen SA to antigen-presenting cells, significantly induces the production of serum-specific antibodies, and activates mucosal immune responses. It demonstrates potential as a carrier and adjuvant for developing mucosal vaccines.

Objective:To evaluate the correlation between preoperative platelet function and in-hospital mortality in patients with acute Stanford A aortic dissection(ATAAD) undergoing emergency surgery.Methods:ATAAD emergency surgical patients who underwent preoperative thromboelastography(TEG) examination at three cardiovascular disease hospitals from January 2018 to December 2023 were consecutively selected in this study. The patients were divided into two groups according to whether the patient survived to discharge.Results:867 patients were included in this study. The in-hospital mortality was 11.2%(97 cases). Compared with the DG group(97 cases), the age, pericardial effusion volume, lactate concentration, and MA value of patients in the SG group(770 cases) were higher( P<0.001). Factors independently associated with in-hospital mortality were age(>60 years old), coronary hypoperfusion, pericardial effusion volume(>200.00 ml), and MA value(<60.6 mm). There was a correlation between MA value and in-hospital mortality( P=0.012), and the mediating effect between MA value and platelet count was not significant. Conclusion:There is a correlation between preoperative platelet function and in-hospital in ATAAD patients, and improving platelet function may be one of the important ways to improve the clinical prognosis of those patients.

Objective:To investigate the dynamic changes of inflammatory biomarkers in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support after cardiac surgery, and evaluate their predictive value for in-hospital mortality.Methods:The retrospective study included 212 patients who underwent VA-ECMO support following cardiac surgery at Beijing Anzhen Hospital, Capital Medical University, from January 2021 to May 2024. Baseline characteristics and inflammatory markers during ECMO support including procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen (FBG) were collected. Univariate analysis, ROC curves, and multivariate logistic regression were performed to assess the association of these indicators with outcomes. Results:On day 3 post-ECMO, mean PCT and CRP levels were significantly higher in the deceased group (87 cases) than in the survival group (125 cases). PCT demonstrated an area under the curve ( AUC) of 0.750 (95% CI: 0.680-0.819) for predicting mortality, while CRP had an AUC of 0.701(95% CI: 0.625-0.778). No significant differences were observed in FBG, NLR, or PLR between the two groups. Lactate levels at 24 h post-ECMO ( AUC=0.723) and SOFA scores ( OR=2.511, AUC=0.713) were also significantly associated with mortality risk in the deceased group ( P<0.05). Conclusion:Dynamic increases in PCT and CRP are independent predictors of in-hospital mortality in cardiac surgery patients supported by ECMO. Elevated lactate levels and SOFA scores, aligning with previous studies, reflect severe tissue hypoperfusion and multi-organ dysfunction in non-survivors, underscoring the necessity of dynamic monitoring of inflammatory and organ function markers for prognosis assessment.

Objective:To investigate the relationship between the number of residual tears in visceral artery segment and vascular remodeling after thoracic aortic endovascular repair (TEVAR).Methods:A total of 100 patients diagnosed with complicated Stanford type B aortic dissection (cTBAD) and treated with TEVAR in our hospital from June 2018 to June 2023 were collected retrospectively as study objects, and were divided into benign remodeling group (58 cases) and non-benign remodeling group (42 cases) according to prognosis. The clinical data, imaging indexes before and after operation, and early postoperative morphological characteristics were compared between the two groups. The independent influencing factors of internal artery remodeling after operation were analyzed by multivariate logistic analysis. Cox proportional risk regression was used to analyze the association between the number of residual tears in visceral artery segments and non-benign remodeling at different disease stages. The relationship between the number of residual tears and non-benign remodeling of visceral artery segments was analyzed by the restricted cubic spline method combined with spline function and logistic regression. Results:Compared with the benign remodeling group, the age and disease stage of the non-benign remodeling group were significantly increased ( P<0.05). After operation, the diameter and area of celiac trunk (CAT), superior mesenteric artery (SMA), left renal artery (LRA) and right renal artery (RRA) were significantly increased ( P<0.05), while the diameter and area of CAT, SMA and LRA were significantly decreased ( P<0.05). The maximum diameter of the lumen, the number of residual lacerations in the visceral artery segment and the number of lumen originating from the lumbar artery were significantly increased ( P<0.05). Further logistic regression analysis showed that age, disease stage, plane true lumen area and plane thrombus area of CAT and SMA, plane true lumen area of LRA and RRA, and number of residual tears of visceral artery segment were independent factors influencing the remodeling of internal arteries after surgery. Cox proportional risk regression analysis showed that the number of residual visceral artery segments was significantly correlated with non-benign remodeling under different disease stages. The multiplicative interaction terms of the number of residual visceral artery segments and disease stages were 0.028 and 0.031 in people aged ≤58.7 years old and>58.7 years old, respectively. Restricted cubic spline analysis showed that regardless of age and disease stage, there was a nonlinear dose-response relationship between the number of residual tears in visceral artery segment and the intensity of non-benign remodeling association, and the number of residual tears in visceral artery segment ≥2 significantly increased the risk of non-benign remodeling. Conclusion:The number of residual tears in visceral artery segment was significantly correlated with vascular remodeling after TEVAR, and the correlation strength with non-benign remodeling showed a nonlinear dose-response relationship. When the number of residual tears in visceral artery segment was ≥2, the risk of non-benign remodeling was significantly increased.

Objective:Bibliometric analysis was performed to map scientific knowledge landscape, so that to explore the research status and future trends in the field of carbapenem-resistant Gram-negative bacteria (CRGNB) over the past decade.Methods:Literature on CRGNB published between January 1st, 2015 and December 31st, 2024 was retrieved from the China National Knowledge Internet (CNKI) database and Web of Science Core Collection (WoSCC). VOSviewer and CiteSpace were used for bibliometric analysis.Results:A total of 3 340 Chinese and 10 761 English publications were included in this study. The annual Chinese publications remained stable, while English publications exhibited a linear growth. It was anticipated that the English publications would decline in the forthcoming years, although remaining high. China contributed the highest number of publications, and Zhejiang University was the institution with the largest number of publications. Bonomo RA, Chen L, etc. were high-impact authors in the field of CRGNB and had formed a stable cooperative group. Antimicrobial Agents and Chemotherapy was the journal with the largest number of publications. High-frequency keywords in the domain of CRGNB were comprehensively categorized into four distinct clusters, including carbapenem resistance mechanisms and gene transmission, antimicrobial drugs and combination therapy, management of critically ill patients, and infections and colonization. It was imperative to acknowledge the significance of all of these research areas. Burst word analysis suggested that carbapenem-resistant Enterobacterales virulence genes as well as new isoforms of Klebsiella pneumoniae carbapenemase (KPC) had become a research hotspot. Conclusions:The issue of carbapenem resistance remains a significant concern. Current research focus on the resistance mechanisms and antimicrobial agents, highlighting its significant academic advancement and practical applications. Fostering international collaboration through academic exchanges between research teams worldwide is imperative to establish robust cooperative relationships, facilitate multidisciplinary cooperation, and promote high-quality research.

AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

As a key member of the insulin-like growth factor family， insulin-like growth factor-‍Ⅰ （IGF-‍Ⅰ） is mainly synthesized in the liver and is widely distributed in the human body， and it is involved in the physiological processes such as cell proliferation， differentiation， metabolism， and apoptosis. Studies have shown that the level of IGF-‍Ⅰ is negatively correlated with the severity of liver cirrhosis， and IGF-‍Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis， promoting DNA damage repair， and regulating lipid metabolism. Monitoring of IGF-‍Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis， and stimulating the action pathway of IGF-‍Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-‍Ⅰ in liver cirrhosis， in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.