1.Prediction of one-day creatinine excretion in Japanese schoolchildren based on anthropometric measurements.
Sayaka KATO ; Yuki ITO ; Asako NAKAGAWA ; Kyoko MINATO ; Mst Sarmin AKTAR ; Mio MIYAKE ; Shogo NAKANE ; Michihiro KAMIJIMA
Environmental Health and Preventive Medicine 2025;30():97-97
BACKGROUND:
The creatinine (Cre) concentration in urine is used as an adjustment factor in chemical exposure and nutritional intake assessments. Because Cre excretion varies by sex, age, race, and anthropometric measurements such as height and weight, developing a method suitable for estimating one-day Cre excretion is necessary. Accordingly, this study aimed to develop a predictive equation for individual one-day Cre excretion in Japanese school children.
METHODS:
Urine samples were collected from 113 boys and 91 girls (aged 6-12 years) from the Aichi Prefecture, Japan, who were free from diseases affecting the renal, muscle, or nervous systems. Urinary concentrations and one-day excreted amounts of Cre were measured and compared with the values obtained using previously reported equations or a fixed value, totaling 11 methods. Subsequently, we developed a new equation using machine learning and multiple regression analyses. Additionally, the estimated one-day sodium excretion value calculated using this equation was compared with the measured value.
RESULTS:
Among the 11 methods to predict Cre excretion, 7 overestimated-5 of which showed a positive trend bias with larger differences at higher average concentrations-and 3 underestimated-2 of which showed a negative trend bias with larger differences at lower average concentrations. A new machine learning model using sex, age, and body surface area (calculated from height and weight) yielded the most accurate prediction. Multiple regression analysis, which demonstrated the most accurate prediction, used sex, age, and body surface area as independent variables with or without the first void Cre concentration divided by urination duration from the previous night's urination to the first void. Moreover, the difference in one-day sodium excretion from first-void urine predicted using our newly developed Cre equation increased as the measured values increased.
CONCLUSIONS:
Our study suggests that the estimation of one-day Cre excretion based on sex, age, and body surface area is most appropriate for Japanese schoolchildren, particularly in assessing their chemical exposure and dietary nutrient intake.
TRIAL REGISTRATION
Trial registration is not applicable as this observational study did not involve any intervention or randomization requiring registration in a clinical trials registry.
Humans
;
Child
;
Female
;
Male
;
Japan
;
Creatinine/urine*
;
Anthropometry
;
East Asian People
3.Augmented renal clearance in neurocritical patients: An epidemiological investigation and risk-factor analysis.
Qile XIAO ; Bohan LUO ; Hainan ZHANG ; Xiaomei WU
Journal of Central South University(Medical Sciences) 2024;49(11):1711-1721
OBJECTIVES:
Augmented renal clearance (ARC), in contrast to renal dysfunction, refers to enhanced renal elimination of circulating solutes compared to the expected baseline. Although patients may present with normal serum creatinine (Scr) levels, the incidence of ARC is high in intensive care unit (ICU) settings. ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics. However, limited research exists on the incidence and risk factors of ARC in the ICU, and even fewer data are available specifically for neurological ICU (NICU). This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.
METHODS:
We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation. ARC was defined as a CrCl≥130 mL/(min·1.73 m2) sustained for more than 50% of the duration of the NICU stay. A total of 208 neurocritically ill patients were assigned into an ARC group (n=52) and a non-ARC (N-ARC) group (n=156). Clinical characteristics were compared between the 2 groups. Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.
RESULTS:
The incidence of ARC among neurocritically ill patients was 25.00%. Of the 74 patients with normal CrCl, 20 (27.03%) gradually developed ARC during hospitalization. Compared with the N-ARC group, the patients of the ARC group were younger (P<0.001), with a higher proportion of females (P=0.048) and a lower admission mean arterial pressure (MAP) (P=0.034). Moreover, patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group (P<0.001). In binary Logistic regression analysis, younger age (OR=0.903, 95% CI 0.872 to 0.935) and severe bacterial infections (OR=6.270, 95% CI 2.568 to 15.310) were significant predictors of ARC.
CONCLUSIONS
ARC is relatively common in the NICU. A considerable number of patients with initially normal renal function developed ARC during hospitalization. Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.
Humans
;
Risk Factors
;
Female
;
Male
;
Retrospective Studies
;
Creatinine/blood*
;
Middle Aged
;
Intensive Care Units
;
Aged
;
Adult
;
Incidence
;
Critical Illness
;
Renal Elimination
;
Kidney/metabolism*
4.Clinical value of arterial stiffness assessment on risk prediction of vascular stiffness in the octogenarian elderly.
Yu Jia WANG ; Zheng Hui GU ; Xue Ping WU ; Zhi Yi FANG ; Tian Hu WANG ; Shan GAO ; Xue YANG ; Xiao Ying SHEN ; Ting Yu ZHOU ; Qi ZHANG ; Jun Xia LI ; Feng CAO
Chinese Journal of Cardiology 2023;51(10):1069-1074
Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.
Aged, 80 and over
;
Humans
;
Male
;
Aged
;
Female
;
Ankle Brachial Index
;
Vascular Stiffness/physiology*
;
Octogenarians
;
Retrospective Studies
;
Cross-Sectional Studies
;
Alanine Transaminase
;
Alkaline Phosphatase
;
Creatinine
;
Sclerosis
;
Pulse Wave Analysis
;
Risk Factors
;
Amylases
;
Lipoproteins, HDL
;
Cholesterol
5.Clinical value of arterial stiffness assessment on risk prediction of vascular stiffness in the octogenarian elderly.
Yu Jia WANG ; Zheng Hui GU ; Xue Ping WU ; Zhi Yi FANG ; Tian Hu WANG ; Shan GAO ; Xue YANG ; Xiao Ying SHEN ; Ting Yu ZHOU ; Qi ZHANG ; Jun Xia LI ; Feng CAO
Chinese Journal of Cardiology 2023;51(10):1069-1074
Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.
Aged, 80 and over
;
Humans
;
Male
;
Aged
;
Female
;
Ankle Brachial Index
;
Vascular Stiffness/physiology*
;
Octogenarians
;
Retrospective Studies
;
Cross-Sectional Studies
;
Alanine Transaminase
;
Alkaline Phosphatase
;
Creatinine
;
Sclerosis
;
Pulse Wave Analysis
;
Risk Factors
;
Amylases
;
Lipoproteins, HDL
;
Cholesterol
6.Treatment outcome of laparoscopic partial nephrectomy in patients with renal tumors of moderate to high complexity.
Min QIU ; You Long ZONG ; Bin Shuai WANG ; Bin YANG ; Chu Xiao XU ; Zheng Hui SUN ; Min LU ; Lei ZHAO ; Jian LU ; Cheng LIU ; Xiao Jun TIAN ; Lu Lin MA
Journal of Peking University(Health Sciences) 2023;55(5):833-837
OBJECTIVE:
To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10).
METHODS:
In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range).
RESULTS:
There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m2; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died).
CONCLUSION
Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.
Male
;
Female
;
Humans
;
Creatinine
;
Retrospective Studies
;
Kidney Neoplasms/pathology*
;
Nephrectomy/methods*
;
Treatment Outcome
;
Laparoscopy
;
Hemoglobins
7.Clinical Characteristics and Risk Factors for 30-Day Mortality in Patients with Hematologic Diseases Infected by Carbapenem-Resistant Organisms.
Xin-Yue CHEN ; Chen-Rui HOU ; Jie ZHAO ; Shao-Long HE ; Xin-Yi LU ; Xiao-Ye GUO ; Rui-Xue WANG ; Liang-Ming MA ; Jun-Ni WEI ; Wei-Wei TIAN
Journal of Experimental Hematology 2023;31(4):1199-1204
OBJECTIVE:
To explore the clinical characteristics of hospitalized patients with hematologic diseases complicated with carbapenem-resistant organisms (CRO) infection and analyze the risk factors of 30-day all-cause mortality.
METHODS:
The clinical data and laboratory test data of 77 hospitalized patients with hematologic diseases complicated with CRO infection in department of hematology of the Third Hospital of Shanxi Medical University from January 2015 to December 2020 were retrospectively analysed, the risk factors of 30-day all-cause mortality after CRO infection were analyzed by multivariate logistic regression.
RESULTS:
Among the total of 77 patients with hematologic diseases complicated with CRO infection, 29 died and 48 survived within 30 days of infection, with a case fatality rate of 37.66%. A total of 93 strains of CRO were isolated from these patients, of which Acinetobacter baumannii had the highest detection rate (25.81%, 24/93), followed by Pseudomonas aeruginosa (18.28%, 17/93). The lung was the most common site of CRO infection. The detected pathogens were highly resistant to carbapenems, and 64.52% (60/93) of the pathogens were resistant to imipenem with minimum inhibitory concentration (MIC)≥16 μg/ml. The results of the univariate analysis showed that albumin concentration <25 g/L (P =0.048), serum creatinine concentration≥120 μmol/L (P =0.023), age-adjusted Charlson comorbidity index (ACCI) (P =0.037) and primary treatments (supportive treatment, immunosuppressive therapy, chemotherapy, HSCT) (P =0.048) were significantly associated with 30-day all-cause mortality after infection. The results of multivariate logistic regression analysis showed that when CRO infection confirmed, albumin concentration <25 g/L (P =0.014, OR=6.171), serum creatinine concentration≥120 μmol/L (P =0.009, OR=10.867) were independent risk factors for 30-day mortality of patients with hematologic diseases complicated with CRO infection.
CONCLUSION
The mortality rate of CRO-infected patients with hematologic diseases is high. The detected pathogenic bacteria are highly resistant to imipenem. The albumin concentration <25 g/L and the serum creatinine concentration≥ 120 μmol/L at diagnosis of CRO infection were independent risk factors for 30-day mortality of the patients with hematologic diseases.
Humans
;
Carbapenems/pharmacology*
;
Retrospective Studies
;
Creatinine
;
Hematologic Diseases
;
Risk Factors
;
Imipenem
;
Albumins
8.Predictive value of hemoglobin to serum creatinine ratio combined with serum uric acid for in-hospital mortality after emergency percutaneous coronary intervention in patients with acute myocardial infarction.
Fengxiang BAO ; Chengjun YANG ; Guohui ZHOU
Chinese Critical Care Medicine 2023;35(9):951-957
OBJECTIVE:
To investigate the clinical value of hemoglobin to serum creatinine ratio (Hb/SCr) combined with blood uric acid (SUA) in predicting in-hospital mortality after emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).
METHODS:
The clinical data of AMI patients who underwent emergency PCI in the First Affiliated Hospital of Kangda College of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. The general information, underlying medical history, blood routine, liver and kidney function, blood coagulation routine, SUA and other indicators were collected from patients. The primary composite endpoint was defined as in-hospital death, including in-hospital all-cause death during PCI and 15-day post-procedure hospitalization. Multivariate Logistic regression was used to analyze factors associated with in-hospital death after emergency PCI in patients with AMI. Multivariate Logistic regression was used to analyze the independent related factors and construct a risk prediction model. The Hosmer-Lemeshow method and receiver operator characteristic curve (ROC curve) were used to test the goodness of fit and predictive effect of the model and correlates, respectively.
RESULTS:
A total of 1 976 patients were enrolled, 92 died in hospital and 1 884 survived. SUA was higher in the death group than that in the survival group (μmol/L: 476.88±132.04 vs. 354.87±105.31, P < 0.01), and the Hb/SCr ratio was significantly lower than that in the survival group (13.84±5.48 vs.19.20±5.74, P < 0.01). Pearson analysis showed a linear negative correlation between SUA and Hb/SCr ratio (r = -0.502, P < 0.01). Logistic regression risk model analysis finally included age [odds ratio (OR) = 0.916], Hb/SCr ratio (OR = 0.182), white blood cell count (WBC, OR = 2.733), C-reactive protein (CRP, OR = 3.611), SUA (OR = 4.667), blood glucose (Glu, OR = 2.726), homocysteine (Hcy, OR = 2.688) 7 factors to construct a risk prediction model, which were independent correlation factors for in-hospital death in AMI patients after emergency PCI (all P < 0.05). Hosmer-Lemeshow test verified the fitting effect of the model, and the result showed P = 0.447. The area under the ROC curve (AUC) of the model for predicting in-hospital death in AMI patients after emergency PCI was 0.764 [95% confidence interval (95%CI) was 0.712-0.816, P = 0.001]. When the cut-off value was 0.565 8, the sensitivity was 70.7%, the specificity was 70.2%, and the Yoden index was 0.410. When Hb/SCr ratio+SUA, SUA, Hb/SCr ratio, Hb and SCr were used to predict in-hospital death in AMI patients after emergency PCI, the AUC of Hb/SCr ratio+SUA was the largest, which was 0.810. When the optimal cut-off value was -0.847, the sensitivity was 77.7%, the specificity was 74.5%, and the Youden index was 0.522.
CONCLUSIONS
Age, SUA, Hb/SCr ratio, WBC, CRP, Glu, and Hcy are independent risk factors for in-hospital death after emergency PCI in AMI patients. The lower the Hb/SCr ratio and the higher the SUA at admission, the higher the risk of in-hospital death after emergency PCI in AMI patients. Hb/SCr ratio combined with SUA has a higher predictive value for in-hospital death after emergency PCI in AMI patients than single index, which is helpful for early identification of high-risk patients.
Humans
;
Hospital Mortality
;
Uric Acid
;
Creatinine
;
Percutaneous Coronary Intervention
;
Retrospective Studies
;
Myocardial Infarction/therapy*
;
Prognosis
9.Applicability of Seven Glomerular Filtration Rate Evaluation Formulas in Dose Adjustment of High Concentration of Methotrexate Chemotherapy in Children with ALL.
Fei LI ; Shan HUANG ; Xia-Xia ZHU ; Jing-Miao ZHANG ; Hong CHEN ; Xiu-Xia LIU ; Qing-Mei DENG
Journal of Experimental Hematology 2023;31(1):280-286
OBJECTIVE:
To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPIscysc, Cockrofi-Gault, CKD-EPIScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL).
METHODS:
One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary.
RESULTS:
All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPIscysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05).
CONCLUSION
Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPIscysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.
Adolescent
;
Humans
;
Male
;
Child
;
Child, Preschool
;
Glomerular Filtration Rate
;
Methotrexate
;
Creatinine
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
;
Renal Insufficiency, Chronic/diagnosis*
10.Effects of interleukin-4-modified gold nanozymes on the full-thickness skin defects in diabetic mice.
Meng Yun YAO ; Ning ZHANG ; Qing ZHANG ; Yi Fei LU ; Yong HUANG ; Deng Feng HE ; Yun Xia CHEN ; Gao Xing LUO
Chinese Journal of Burns 2023;39(1):15-24
Objective: To investigate the effects and mechanism of interleukin-4-modified gold nanoparticle (IL-4-AuNP) on the wound healing of full-thickness skin defects in diabetic mice. Methods: Experimental research methods were adopted. Gold nanoparticle (AuNP) and IL-4-AuNP were synthesized by improving the methods described in published literature. The morphology of those two particles were photographed by transmission electron microscopy, and their particle sizes were calculated. The surface potential and hydration particle size of the two particles were detected by nanoparticle potentiometer and particle size analyzer, respectively. The clearance rate of IL-4-AuNP to hydrogen peroxide and superoxide anion was measured by hydrogen peroxide and superoxide anion kits, respectively. Mouse fibroblast line 3T3 cells were used and divided into the following groups by the random number table (the same below): blank control group, hydrogen peroxide alone group treated with hydrogen peroxide only, hydrogen peroxide+IL-4-AuNP group treated with IL-4-AuNP for 0.5 h and then treated with hydrogen peroxide. After 24 h of culture, the reactive oxygen species (ROS) levels of cells were detected by immunofluorescence method; cell count kit 8 was used to detect relative cell survival rate. The macrophage Raw264.7 mouse cells were then used and divided into blank control group and IL-4-AuNP group that treated with IL-4-AuNP. After 24 h of culture, the expression of arginase 1 (Arg-1) in cells was observed by immunofluorescence method. Twelve male BALB/c mice (mouse age, sex, and strain, the same below) aged 8 to 10 weeks were divided into IL-4-AuNP group and blank control group, treated accordingly. On the 16th day of treatment, whole blood samples were collected from mice for analysis of white blood cell count (WBC), red blood cell count (RBC), hemoglobin level, or platelet count and the level of aspartate aminotransferase (AST), alanine transaminase (ALT), urea, or creatinine. The inflammation, bleeding, or necrosis in the heart, liver, spleen, lung, and kidney tissue of mice were detected by hematoxylin-eosin (HE). Another 36 mice were selected to make diabetic model, and the full-thickness skin defect wounds were made on the back of these mice. The wounds were divided into blank control group, AuNP alone group, and IL-4-AuNP group, with 12 mice in each group, and treated accordingly. On the 0 (immediately), 4th, 9th, and 15th day of treatment, the wound condition was observed and the wound area was calculated. On the 9th day of treatment, HE staining was used to detect the length of neonatal epithelium and the thickness of granulation tissue in the wound. On the 15th day of treatment, immunofluorescence method was used to detect ROS level and the number of Arg-1 positive cells in the wound tissue. The number of samples was 6 in all cases. Data were statistically analyzed with independent sample t test, corrected t test, Tukey test, or Dunnett T3 test. Results: The size of prepared AuNP and IL-4-AuNP were uniform. The particle size, surface potential, and hydration particle size of AuNP and IL-4-AuNP were (13.0±2.1) and (13.9±2.5) nm, (-45.8±3.2) and (-20.3±2.2) mV, (14±3) and (16±4) nm, respectively. For IL-4-AuNP, the clearance rate to hydrogen peroxide and superoxide anion were (69±4)% and (52±5)%, respectively. After 24 h of culture, the ROS level of 3T3 in hydrogen peroxide alone group was significantly higher than that in blank control group (q=26.12, P<0.05); the ROS level of hydrogen peroxide+IL-4-AuNP group was significantly lower than that in hydrogen peroxide alone group (q=25.12, P<0.05) and close to that in blank control group (P>0.05). After 24 h of culture, the relative survival rate of 3T3 cells in hydrogen peroxide+IL-4-AuNP group was significantly higher than that in hydrogen peroxide alone group (t=51.44, P<0.05). After 24 h of culture, Arg-1 expression of Raw264.7 cells in IL-4-AuNP group was significantly higher than that in blank control group (t'=8.83, P<0.05).On the 16th day of treatment, there were no significant statistically differences in WBC, RBC, hemoglobin level, or platelet count and the level of AST, ALT, urea, or creatinine of mice between blank control group and IL-4-AuNP group (P>0.05). No obvious inflammation, bleeding or necrosis was observed in the heart, liver, spleen, lung, and kidney of important organs in IL-4-AuNP group, and no significant changes were observed compared with blank control group. On the 0 and 4th day of treatment, the wound area of diabetic mice in blank control group, AuNP alone group, and IL-4-AuNP group had no significant difference (P>0.05). On the 9th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 9.45 and 14.87, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=5.42, P<0.05). On the 15th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 4.84 and 20.64, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=15.80, P<0.05); moreover, inflammations such as redness and swelling were significantly reduced in IL-4-AuNP group compared with the other two groups. On the 9th day of treatment, compared with blank control group and AuNP alone group, the length of neonatal epithelium in the wound of diabetic mice in IL-4-AuNP group was significantly longer (all P<0.05), and the thickness of the granulation tissue in the wound was significantly increased (with q values of 11.33 and 9.65, respectively, all P<0.05). On the 15th day of treatment, compared with blank control group, ROS levels in wound tissue of diabetic mice in AuNP alone group and IL-4-AuNP group were significantly decreased (P<0.05). On the 15th day of treatment, the number of Arg-1 positive cells in the wounds of diabetic mice in IL-4-AuNP group was significantly more than that in blank control group and AuNP alone group, respectively (all P<0.05). Conclusions: IL-4-AuNP is safe in vivo, and can improve the oxidative microenvironment by removing ROS and induce macrophage polarization towards M2 phenotype, thus promote efficient diabetic wound healing and regeneration of full-thickness skin defects in diabetic mice.
Mice
;
Male
;
Animals
;
Interleukin-4
;
Gold/pharmacology*
;
Diabetes Mellitus, Experimental
;
Creatinine
;
Hydrogen Peroxide
;
Reactive Oxygen Species
;
Superoxides
;
Metal Nanoparticles
;
Soft Tissue Injuries
;
Antibodies
;
Inflammation
;
Necrosis
;
Hemoglobins

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