The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

Objective To explore the characteristics of TCM in the treatment of asymptomatic hyperuricemia based on data mining.Methods Clinical literature on the TCM treatment of asymptomatic hyperuricemia in CNKI,Wanfang Data,VIP and SinoMed was retrieved.After screening,the prescriptions obtained were input into Excel 2019 database,and SPSS Modeler 18.0,SPSS Statistics 26.0 and Cytoscape 3.9.1 were used for frequency analysis,association rule analysis,clustering analysis and factor analysis.Results A total of 133 articles meeting the criteria were included,and 140 prescriptions were included,involving 202 kinds of Chinese materia medica,with a total frequency of 1 387 times.22 drugs,such as Smilacis Glabrae Rhizoma,Coicis Semen,Dioscoreae Spongiosae Rhizoma,Astrctylodis Rhizoma,were frequently used in the treatment of asymptomatic hyperuricemia.The commonly used drugs were drugs for urine excretion to strain off dampness,tonics,clearing heat,promoting blood circulation and removing blood stasis.The medicinal property was mainly warm,the medicinal taste was mainly sweet,and the meridians were mainly liver,spleen,stomach and kidney meridians.21 groups of medicinal combinations were obtained by high frequency drug association rule analysis,among which the core drug pairs were Coicis Semen-Astrctylodis Rhizoma,Smilacis Glabrae Rhizoma-Dioscoreae Spongiosae Rhizoma-Coicis Semen,Coicis Semen-Astrctylodis Rhizoma-Smilacis Glabrae Rhizoma,etc.Clustering analysis obtained 5 clustering methods,and factor analysis obtained 7 common factors.Conclusion In the TCM treatment of asymptomatic hyperuricemia,the main methods are urine excretion to strain off dampness,strengthening spleen and tonifying qi,and the main drugs are Smilacis Glabrae Rhizoma,Coicis Semen,Dioscoreae Spongiosae Rhizoma,Astrctylodis Rhizoma,which can provide reference for clinical treatment of asymptomatic hyperuricemia.

Objective:To investigate the epidemiological characteristics, genotypes and genetic evolution of respiratory syncytial virus (RSV) isolated in Shanghai from April 2020 to December 2021, which was a period from the COVID-19 outbreak to the phase of regular epidemic prevention and control.Methods:This retrospective study collected the nasopharyngeal secretions or nasopharyngeal aspirates of children with acute respiratory tract infection (ARTI) admitted to the Shanghai Children′s Hospital from April 2020 to December 2021. PCR-capillary electrophoresis and RT-PCR were used for virus identification and the amplification of the gene fragment of the second hypervariable region of RSV G protein. Homology analysis and phylogenetic analysis were conducted using bioinformatics software. Chi-square test was used to compare the detection rates of RSV. Results:A total of 6 211 samples were collected and 13.62% (846/6 211) of them were positive for RSV. The positive rates of RSV in male and female patients were 14.07% (503/3 574) and 13.01% (343/2 637), respectively, with no significant gender difference (χ 2=1.467, P=0.226). The highest detection rate of RSV was found in children ≤6 months of age, and the rate of RSV infection decreased gradually with age (χ 2=352.942, P<0.001). No RSV-positive specimens were detected from April 2020 to August 2020, after which the detection rate of RSV gradually increased with two epidemic peaks occurring from December 2020 to February 2021 and from August to October 2021. The predominant epidemic subtype was RSV subtype B in 2020 and the first 9 months of 2021, which was gradually replaced by RSV subtype A in the last 3 months of 2021. The 176 strains of RSV subtype A obtained in this study were all ON1 genotype, and the nucleotide homology of the Shanghai epidemic strains was 90.20%-99.50%. All of the 250 strains of RSV subtype B were BA9 genotype, and the nucleotide homology of the Shanghai epidemic strains was 90.10%-100.00%. Conclusions:From April 2020 to December 2021, with the regular prevention and control of COVID-19, there is a change in the epidemic season of RSV. The prevalent genotypes of RSV subtypes A and B are ON1 and BA9, respectively, and the subtype A gradually replaces subtype B as the most prevalent subtype.

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P＜0.01,P＜0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.

Objective To investigate the feasibility of granzyme B(GB)promoter-controlled ferritin heavy chain(FTH1)reporter gene expression for monitoring the activation status of chimeric antigen receptor T cells(CAR-T)by magnetic resonance imaging(MRI).Methods Cytotoxic T lymphocytes(CTLs)were screened by Ficoll density gradient centrifugation and flow sorting.The GB promoter and FTH1 gene were ligated together with disialoganglioside 2(GD2)CAR,and lentiviral vectors were transfected into CTLs to construct GD2-CAR-T/pGB-FTH1 cells.GD2-CAR-T/pCMV-FTH1,GD2-CAR-T,and T cells served as control cells.CytoTox96@non-radioactive cytotoxicity was used to detect the killing effect of each group of cells after co-culture with human neuroblastoma cells(SK-N-SH).ELISA was employed to detect the coincubation factor as well as the amount of GB secretion.Western blotting,Prussian blue staining and cellular MRI were applied to detect the expression of the FTH1 gene after co-culture.Results CTLs were successfully obtained,and then GD2-CAR-T/pGB-FTH1,GD2-CAR-T/pCMV-FTH1 and GD2-CAR-T cells were constructed.The killing effect,co-incubation factor and GB secretion of the above 3 groups of cells were significantly higher than those of the T cells,and the level of GB expression was highest at day 1,and then decreased in order at day 3 and day 7 after co-culturing with SK-N-SH cells.The relative expression of FTH1 and iron content of the GD2-CAR-T/pGB-FTH1 cells showed the same trend as GB expression,and the MRI signals were gradually increased.There were no significant differences in the relative expression of FTH1,iron content and MRI signals in the GD2-CAR-T/pCMV-FTH1 cells at all time points.No FTH1 expression or iron aggregation was observed in the GD2-CAR-T and T cells groups.Conclusion MRI based on the FTH1 reporter gene driven by the granzyme B promoter can reflect the GB expression level and tumor killing effect of CAR-T cells,which provides a potential real-time visual means to monitor the cell activation status for CAR-T therapy.