1.A Review and Evaluation of Integrated Disease and Syndrome Animal Models for Hemorrhoids in Traditional Chinese and Western Medicine
Yu BU ; Jinting HOU ; Yuanyuan LI ; Jingtao SHA ; Chenlu XIE ; Wengang WANG ; Xingwei SUN
Laboratory Animal and Comparative Medicine 2026;46(3):357-366
Hemorrhoids are common anorectal diseases with complex pathogenesis, and there is still a lack of ideal experimental animal models for research on their prevention and treatment. In this paper, Chinese and English databases are searched with the keywords "hemorrhoids" and "animal model", and 36 relevant studies are finally included. The shortcomings of existing hemorrhoid animal models in integrating the clinical disease and syndrome characteristics of traditional Chinese and Western medicine are systematically analyzed, and the consistency of various models with clinical practice is evaluated. The studies are divided into four categories according to modeling methods: chemical modeling, physical modeling, biological modeling, and combined modeling. The clinical consistency of modeling is evaluated in combination with the diagnostic points of hemorrhoids in traditional Chinese and Western medicine. The results show that there are significant differences in the reproduction of clinical indicators by different modeling methods. According to clinical consistency, the models can be divided into three grades: high-consistency models are mainly based on combined modeling methods (such as induction by carrageenan combined with norepinephrine hydrochloride), which can more comprehensively simulate core pathological changes such as venous congestion and local inflammation; moderate-consistency models adopt single chemical or physical intervention (such as local inflammation induced by croton oil or vein ligation), which can only reproduce part of the pathological process; low-consistency models mostly adopt direct stimulation, with limited research value for pathological characteristics. Existing animal models have obvious advantages in replicating Western medical structural lesions of hemorrhoids, but they still have obvious defects in simulating the chronic disease course and stably reproducing the characteristics of traditional Chinese medicine syndromes, and a unified standard has not yet been formed for the traditional Chinese medicine evaluation system of models. In conclusion, it is still necessary to further explore the construction of high-quality integrated disease and syndrome animal models for hemorrhoids in traditional Chinese and Western medicine. Future research should integrate the theories of traditional Chinese and Western medicine, adopt multi-factor chronic modeling strategies, and establish a standardized comprehensive evaluation system covering macroscopic signs and microscopic indicators. This paper provides a reference for constructing standardized integrated disease and syndrome animal models of hemorrhoids that conform to the pathological changes of Western medicine and take into account the characteristics of traditional Chinese medicine syndromes, with the aim of providing more effective experimental tools for research on the pathogenesis of hemorrhoids and their integrated prevention and treatment with traditional Chinese and Western medicine.
2.Uterine artery embolization for adenomyosis:evaluation of efficacy and analysis of predictive factors
Hao ZHANG ; Jinlian MA ; Xingwei SUN ; Mingyao WANG ; Yong JIN
Journal of Interventional Radiology 2025;34(7):766-771
Objective To evaluate the efficacy of uterine artery embolization(UAE)for the treatment of adenomyosis(AM)and to discuss the factors predicting efficacy.Methods The clinical data of 44 patients with AM,who received UAE at The Second Affiliated Hospital of Soochow University from January 2020 to August 2022,were retrospectively analyzed.Based on the MRI findings,serum CA125 levels and follow-up dysmenorrhea scores,the efficacy of UAE and the factors predicting efficacy were analyzed.Results A single UAE treatment was performed in all 44 patients with AM.Follow-up check with MRI at 12 months after treatment showed that the mean uterine volume decreased from preoperative(299.60±182.42)cm3 to postoperative(173.14±104.00)cm3,with a volume reduction of 36.64%(P<0.05).The dysmenorrhea score decreased from preoperative(7.70±2.60)points to postoperative(2.20+2.37)points,with a relief rate of 88.64%(P<0.05),and no severe adverse reactions occurred.Enhanced MRI demonstrated that in 30 patients(68.18%)the AM lesions presented as complete necrosis foci.In the patients whose preoperative lesions were completely necrotic,the mean preoperative serum CA125 level was(101.97±60.30)U/mL,the mean ADC value was(1.012+0.271)mm2/s,which were obviously lower than those in the patients whose preoperative lesions were incompletely necrotic(P<0.05).The mean T2 signal ratio(T2SR)value in the patients whose preoperative lesions were completely necrotic was(0.582±0.198),which was significantly higher than that in the patients whose preoperative lesions were incompletely necrotic(P<0.05).The analysis of receiver operating characteristic(ROC)curve showed that the preoperative area under the curve(AUC),sensitivity,and specificity for preoperative CA125 were 0.844,60%and 80%respectively;the AUC,sensitivity,and specificity for preoperative ADC were 0.760,80%and 65%respectively;and the AUC,sensitivity,and specificity for preoperative T2SR were 0.760,80%and 70%respectively.ADC<1.116 × 10-3 mm2/s,T2SR>0.479,and CA125<109.10 U/mL could be used as the reliable predictive factors for the efficacy of UAE treatment for AM.Conclusion UAE can effectively alleviate dysmenorrhea symptoms in patients with AM,and it is clinically safe and effective.ADC,T2SR,and CA125 can be used as the reliable predictive factors for the efficacy of UAE treatment for AM,which are helpful in predicting the lesion response and selecting the reasonable therapeutic options for patients.
3.Preparation and in vitro evaluation of an erythrocyte-based butyrylcholinesterase delivery system
Zhe WANG ; Changwen NING ; Huaying AN ; Xingwei JIANG ; Jun MA ; Fenghua GAO ; Pengyu LIU ; Yanan SUN ; Ru LI ; Jinlong LI ; Yuanyuan YUAN ; Qun YU
Military Medical Sciences 2025;49(6):458-464
Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85%dimer,15%monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P<0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P<0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P<0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P<0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P>0.05).CD47 expression remained unchanged compared to native erythrocytes(P>0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.
4.A comparative study of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter
Longfei CHEN ; Dian WEI ; Xingwei YANG ; Qian ZHANG ; Lihua GUO ; Lei WANG ; Ji LI ; Quan SUN ; Mingyang SHI ; Yiwei YUE ; Zhongying HAN
Chinese Journal of Applied Clinical Pediatrics 2025;40(9):675-679
Objective:To investigate the characteristics and clinical effects of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter (POM) in children.Methods:A randomized controlled study was conducted.The clinical data of 51 children with unilateral POM admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023 were collected.Random number table method was used in the selection of surgical methods.They were divided into the laparoscopic pneumovesical Cohen ureteral replantation group (group A, 22 cases) and the laparoscopic Lich-Gregoir ureteral replantation group (group B, 29 cases) according to the surgical method.The anterior-posterior diameter(APD), maximum ureteral diameter and differential renal function parameters on the affected side were measured by color Doppler ultrasound of the urinary system, and compared between and within the two groups before and after surgery.The operation time, blood loss and postoperative intubation time were compared between the two groups.The incidence of postoperative complications such as reflux, bladder spasm, urinary retention and urinary tract infection was recorded.The independent and paired sample t-tests were used for statistical analysis. Results:The operation time and hematuria duration of group B [(125.7±14.2) min, (1.5±0.6) d] were significantly shorter than those of group A [(142.6±14.7) min, (2.8±0.7) d] (all P<0.05). The APD, maximum ureteral diameter, and differential renal function on the affected side of group A were (21.7±7.9) mm, (11.6±3.2) mm, and (28.2±4.9)% before surgery, and (10.3±4.5) mm, (6.0±2.0) mm and (43.8±4.4)% after surgery, respectively.The APD, maximum ureteral diameter, and differential renal function on the affected side of group B were (21.1±5.6) mm, (11.3±4.6) mm, and (30.2±5.5)% before surgery, and (10.2±4.5) mm, (6.6±2.0) mm, and (42.4±5.2)% after surgery, respectively.There was no statistically significant difference in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the two groups of children (all P>0.05). However, there were statistically significant differences in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the same group of children (all P<0.01). No significant difference was found in intraoperative blood loss, postoperative intubation time, and postoperative complications between the two groups (all P>0.05). Conclusions:Both surgical methods are effective in the treatment of POM in children.Laparoscopic Lich-Gregoir ureteral replantation has advantages of less operation time compared with laparoscopic pneumovesical Cohen ureteral replantation.
5.The effect of remimazolam on modulating the ROS/RAGE/NF-κB signaling pathway in LPS-induced microglial inflammation
Xingwei WU ; Jianying WANG ; Chengxiao GUO ; Ziyi LIU ; Chao SUN ; Fei YU
The Journal of Practical Medicine 2025;41(2):153-161
Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.
6.The intervention of TLR4/NF-κB signaling pathway mediated by Gexia Zhuyu decoction on ulcerative colitis and the effect on intestinal mucosal barrier
Bei HUANG ; Xingwei SUN ; Zhifei HU ; Yuanyuan LI
Journal of Chinese Physician 2025;27(2):220-224
Objective:To investigate the effect of Gexia Zhuyu decoction on Toll-like receptor 4 (TLR4)/Nuclear factor-kappaB (NF-κB) signaling pathway on ulcerative colitis and intestinal mucosal barrier.Methods:A total of 86 cases of ulcerative colitis admitted to Xi′an Traditional Chinese Medicine (TCM) Hospital from March 2019 to July 2023 were prospectively included and divided into observation group and control group according to random number table method, with 43 cases in each group. The control group was treated with mesalazine enteric-coated tablets; The observation group was treated with mesalazine enteric-coated tablets combined with Gexia Zhuyu decoction for removing stasis. The clinical efficacy of the two groups was compared in terms of TCM syndrome score, intestinal mucosal barrier function index [diamine oxidase (DAO), D-lactic acid (D-LA)], TLR4/NF-κB signaling pathway expression and inflammatory factor index [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] before and after treatment. The occurrence of adverse reactions was also compared.Results:The total effective rate of observation group was higher than that of control group (χ 2=4.074, P=0.044). Before treatment, there was no significant difference in TCM syndrome scores between the two groups (all P>0.05). After treatment, the TCM syndrome scores of both groups were lower than those before treatment (all P<0.05), and the TCM syndrome scores of the observation group were lower than those of the control group (all P<0.05). Before treatment, there were no significant differences in D-LA and DAO levels between the two groups (all P>0.05). After treatment, the levels of D-LA and DAO in both groups were lower than before treatment (all P<0.05), and the levels of D-LA and DAO in the observation group were lower than those in the control group (all P<0.05). After treatment, the mRNA expressions of TLR4 and NF-κB in both groups were decreased compared with those before treatment, and the mRNA expressions of TLR4 and NF-κB in the observation group were lower than those in the control group (all P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were decreased compared with those before treatment (all P<0.05), and the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ 2=2.346, P=0.126). Conclusions:The application of Gexia Zhuyu decoction in the treatment of ulcerative colitis can not only effectively improve the clinical symptoms, signs and intestinal mucosal barrier function, but also improve the inflammatory response by mediating TLR4/NF-κB signaling pathway.
7.A comparative study of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter
Longfei CHEN ; Dian WEI ; Xingwei YANG ; Qian ZHANG ; Lihua GUO ; Lei WANG ; Ji LI ; Quan SUN ; Mingyang SHI ; Yiwei YUE ; Zhongying HAN
Chinese Journal of Applied Clinical Pediatrics 2025;40(9):675-679
Objective:To investigate the characteristics and clinical effects of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter (POM) in children.Methods:A randomized controlled study was conducted.The clinical data of 51 children with unilateral POM admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023 were collected.Random number table method was used in the selection of surgical methods.They were divided into the laparoscopic pneumovesical Cohen ureteral replantation group (group A, 22 cases) and the laparoscopic Lich-Gregoir ureteral replantation group (group B, 29 cases) according to the surgical method.The anterior-posterior diameter(APD), maximum ureteral diameter and differential renal function parameters on the affected side were measured by color Doppler ultrasound of the urinary system, and compared between and within the two groups before and after surgery.The operation time, blood loss and postoperative intubation time were compared between the two groups.The incidence of postoperative complications such as reflux, bladder spasm, urinary retention and urinary tract infection was recorded.The independent and paired sample t-tests were used for statistical analysis. Results:The operation time and hematuria duration of group B [(125.7±14.2) min, (1.5±0.6) d] were significantly shorter than those of group A [(142.6±14.7) min, (2.8±0.7) d] (all P<0.05). The APD, maximum ureteral diameter, and differential renal function on the affected side of group A were (21.7±7.9) mm, (11.6±3.2) mm, and (28.2±4.9)% before surgery, and (10.3±4.5) mm, (6.0±2.0) mm and (43.8±4.4)% after surgery, respectively.The APD, maximum ureteral diameter, and differential renal function on the affected side of group B were (21.1±5.6) mm, (11.3±4.6) mm, and (30.2±5.5)% before surgery, and (10.2±4.5) mm, (6.6±2.0) mm, and (42.4±5.2)% after surgery, respectively.There was no statistically significant difference in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the two groups of children (all P>0.05). However, there were statistically significant differences in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the same group of children (all P<0.01). No significant difference was found in intraoperative blood loss, postoperative intubation time, and postoperative complications between the two groups (all P>0.05). Conclusions:Both surgical methods are effective in the treatment of POM in children.Laparoscopic Lich-Gregoir ureteral replantation has advantages of less operation time compared with laparoscopic pneumovesical Cohen ureteral replantation.
8.The effect of remimazolam on modulating the ROS/RAGE/NF-κB signaling pathway in LPS-induced microglial inflammation
Xingwei WU ; Jianying WANG ; Chengxiao GUO ; Ziyi LIU ; Chao SUN ; Fei YU
The Journal of Practical Medicine 2025;41(2):153-161
Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.
9.The intervention of TLR4/NF-κB signaling pathway mediated by Gexia Zhuyu decoction on ulcerative colitis and the effect on intestinal mucosal barrier
Bei HUANG ; Xingwei SUN ; Zhifei HU ; Yuanyuan LI
Journal of Chinese Physician 2025;27(2):220-224
Objective:To investigate the effect of Gexia Zhuyu decoction on Toll-like receptor 4 (TLR4)/Nuclear factor-kappaB (NF-κB) signaling pathway on ulcerative colitis and intestinal mucosal barrier.Methods:A total of 86 cases of ulcerative colitis admitted to Xi′an Traditional Chinese Medicine (TCM) Hospital from March 2019 to July 2023 were prospectively included and divided into observation group and control group according to random number table method, with 43 cases in each group. The control group was treated with mesalazine enteric-coated tablets; The observation group was treated with mesalazine enteric-coated tablets combined with Gexia Zhuyu decoction for removing stasis. The clinical efficacy of the two groups was compared in terms of TCM syndrome score, intestinal mucosal barrier function index [diamine oxidase (DAO), D-lactic acid (D-LA)], TLR4/NF-κB signaling pathway expression and inflammatory factor index [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] before and after treatment. The occurrence of adverse reactions was also compared.Results:The total effective rate of observation group was higher than that of control group (χ 2=4.074, P=0.044). Before treatment, there was no significant difference in TCM syndrome scores between the two groups (all P>0.05). After treatment, the TCM syndrome scores of both groups were lower than those before treatment (all P<0.05), and the TCM syndrome scores of the observation group were lower than those of the control group (all P<0.05). Before treatment, there were no significant differences in D-LA and DAO levels between the two groups (all P>0.05). After treatment, the levels of D-LA and DAO in both groups were lower than before treatment (all P<0.05), and the levels of D-LA and DAO in the observation group were lower than those in the control group (all P<0.05). After treatment, the mRNA expressions of TLR4 and NF-κB in both groups were decreased compared with those before treatment, and the mRNA expressions of TLR4 and NF-κB in the observation group were lower than those in the control group (all P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were decreased compared with those before treatment (all P<0.05), and the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ 2=2.346, P=0.126). Conclusions:The application of Gexia Zhuyu decoction in the treatment of ulcerative colitis can not only effectively improve the clinical symptoms, signs and intestinal mucosal barrier function, but also improve the inflammatory response by mediating TLR4/NF-κB signaling pathway.
10.Association Between the Aggregate Index of Systemic Inflammation and Albuminuria:A Cross-Sectional Study of National Health and Nutrition Examination Survey 2007-2018
Lirong SUN ; Xingwei HUO ; Shanshan JIA ; Xiaoping CHEN
Journal of Sichuan University (Medical Sciences) 2024;55(3):671-679
Objective Prior studies have established a connection between albuminuria and various inflammatory reactions,highlighting that an increase in C-reactive protein by 1 mg/L increases the likelihood of albuminuria by 2%.Recent investigations indicate a positive correlation between the systemic immune-inflammation index(SII)and increased urinary protein excretion.In addition,elevated levels of the systemic inflammatory response index(SIRI)also correlate with a higher prevalence of albuminuria.The aggregate index of systemic inflammation(AISI)offers a more comprehensive indicator of inflammation,providing an extensive assessment of systemic inflammatory status compared to SII and SIRI.Yet,the specific relationship between AISI and albuminuria remains unclear.This study aims to explore this association in U.S.adults.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)for 2007-2018,excluding pregnant women and individuals under 18.Cases with missing data on AISI,urinary albumin concentration,and other covariates were also excluded.AISI was computed using the formula:AISI=(platelet count×neutrophil count×monocyte count)/lymphocyte count.Albuminuria was defined as the urinary albumin-to-creatinine ratio exceeding 30 mg/g.Continuous variables were presented in the form of the mean±standard error,and categorical variables in percentages.We utilized weighted t-tests and chi-square tests for baseline comparisons.We applied weighted multivariable logistic regression and generalized additive models(GAM)to explore the association between AISI and albuminuria and to assess potential nonlinear relationships.Results The study included 32 273 participants,with an average age of(46.75±0.24)years old.The cohort comprised 48.73% males and 51.27% females.The prevalence of albuminuria was 9.64%.The average logarithmic value of log2AISI was 7.95±0.01,and were categorized into tertiles as follows:Quartile 1(Q1)(4.94 to 7.49),Q2(7.49 to 8.29),and Q3(8.29 to 10.85).As log2AISI increased,so did the prevalence of hypertension,diabetes,congestive heart failure,and albuminuria,all showing statistically significant increases(P<0.001).Similarly,the use of antihypertensive,lipid-lowering,and hypoglycemic drugs was also more prevalent(P<0.001).Statistically significant differences were observed across the three groups concerning age,race and ethnicity,formal education,alcohol consumption,smoking status,systolic and diastolic blood pressures,body mass index,estimated glomerular filtration rate,HbA1c,alanine aminotransferase,aspartate aminotransferase,albumin,creatinine,uric acid,and high-density lipoprotein cholesterol(P<0.05).However,no significant differences were noted in the total cholesterol or the sex ratios among the groups.The association between log2AISI and albuminuria was assessed using weighted multivariable logistic regression,and the detailed results are presented in Table 2.In model 1,without adjusting for covariates,each unit increase in log2AISI was associated with a 32% increase in the risk of albuminuria(odds ratio[OR]=1.32,95% confidence interval[CI]:1.27-1.38,P<0.001).Model 2 was adjusted for age,gender,race,and education level,and showed a similar trend,with each unit increase in log2AISI associated with a 31% increased risk(OR=1.31,95% CI:1.26-1.37,P<0.001).Model 3,which was further adjusted for all covariates,revealed that each unit increase in log2AISI was associated with a 20% increase in the risk of albuminuria(OR=1.20,95% CI:1.15-1.26,P<0.001).The study also transformed log2AISI from a continuous to a categorical variable for analysis.Compared with Q1,the risk of albuminuria in Q3,after adjusting for all covariates,significantly increased(OR=1.37,95% CI:1.22-1.55,P<0.001).Q2 also demonstrated a higher risk compared with Q1(OR=1.13,95% CI:1.06-1.36,P=0.004).The trend test indicated a dose-effect relationship between increasing log2AISI and the rising risk of albuminuria.GAM revealed a nonlinear relationship between log2AISI and albuminuria,with distinct trends noted between sexes.Segmented regression based on turning points showed significant effects among women,although the slope difference between the segments was not significant.In men,a significant threshold effect was observed;below the log2AISI of 7.25,increases in log2AISI did not enhance the risk of albuminuria,but above this threshold,the risk significantly increased.As part of a sensitivity analysis,weighted multivariable logistic regression was performed by changing the outcome variable to macroalbuminuria and adjusting for all covariates.The analysis showed that for every unit increase in log2AISI,the risk of developing macroalbuminuria increased by 31% (OR=1.31,95% CI:1.15-1.49,P<0.001).Compared with Q1,the risk of albuminuria in Q3 increased by 69% (OR=1.69,95% CI:1.27-2.25,P<0.001),and in Q2,it increased by 40% (OR=1.40,95% CI:1.03-1.92,P=0.030).Subgroup analysis and interaction results showed that the positive association between AISI and proteinuria risk was stronger in men than in women.Similarly,the association was stronger in people with hypertension compared with those with normal blood pressure,and higher in overweight people compared with those of normal weight.Furthermore,smokers and drinkers showed a stronger positive association between AISI and the risk of proteinuria than non-smokers and non-drinkers do.These results suggest that sex,blood pressure,body mass index,smoking,and alcohol consumption interact with AISI to influence the risk of proteinuria.Conclusion There is a robust positive association between AISI and increased risks of albuminuria in US adults.As log2AISI increases,so does the risk of albuminuria.However,further validation of this conclusion through large-scale prospective studies is warranted.

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