Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.@*METHODS@#The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.@*RESULTS@#For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.@*CONCLUSION@#It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Perfil sociodemográfico e laboratorial dos pacientes submetidos à hemodiálise em um centro de referência do Estado do Ceará / Sociodemographic and laboratory profile of patients undergoing hemodialysis in a reference center in the State of Ceará / Perfil sociodemográfico y de laboratorio de dos pacientes sometidos a hemodiálisis en un centro de referencia del Estado de Ceará

A Doença Renal Crônica (DRC) é uma importante redução da função renal que causa alterações no metabolismo dos indivíduos. Para acompanhar a progressão da DRC e prevenir possíveis complicações, foi realizada uma pesquisa para avaliar o perfil sociodemográfico, bioquímico e hematológico de pacientes com Insuficiência Renal Crônica (IRC) submetidos a hemodiálise. Esta pesquisa foi quantitativa, descritiva e transversal de caráter retrospectivo, realizada por meio da análise de dados secundários contidos nos prontuários dos pacientes. A coleta de dados ocorreu no Centro de Hemodiálise da cidade de Russas, no Ceará. A amostra foi constituída por 161 pacientes com DRC, sendo 63,35% do sexo masculino e 85,71% pardos, com uma idade média de 54,39 anos. Desses, 63,97% tinham entre 2 e 10 anos de tratamento e 57,76% possuíam ensino fundamental incompleto. 19,25% residiam em Russas. Resultados: Após a hemodiálise, os resultados mostraram 44 mg/dL de Ureia, 48,44% dos pacientes com valores normais. A hemoglobina e hematócrito médios foram 11,8 g/dL e 33,7%, respectivamente, sendo que 63,35% tiveram valores reduzidos. 85,10% dos pacientes tiveram contagem de plaquetas normal, 72,04% níveis adequados de ferro e albumina, 52,79% tiveram níveis elevados de ferritina, 23,61% redução de transferrina e níveis lipídicos satisfatórios. 79,50% apresentaram níveis séricos de potássio dentro da normalidade, 12,42% de fósforo acima do normal, 85,09% de cálcio dentro dos valores normais, 39,13% de PTHi normais e 86,33% de glicose dentro dos valores considerados normais. Com base nos resultados, concluiu-se que todos os pacientes em tratamento hemodialítico apresentam diversas alterações em decorrência da DRC e do próprio processo de tratamento. Portanto, a realização de exames para avaliar ou monitorar possíveis complicações da IRC é essencial para criar estratégias e intervenções mais eficazes, que melhorem a assistência prestada a esses pacientes e, consequentemente, da qualidade e expectativa de vida dos mesmos.

Chronic Kidney Disease (CKD) is an important reduction in kidney function that causes changes in the metabolism of individuals. To monitor the progression of CKD and prevent possible complications, a survey was carried out to assess the sociodemographic, biochemical and hematological profile of patients with Chronic Renal Failure (CRF) undergoing hemodialysis. This research was quantitative, descriptive and cross-sectional with a retrospective character, carried out through the analysis of secondary data contained in the patients' medical records. Data collection took place at the Hemodialysis Center in the city of Russas, Ceará. The sample consisted of 161 patients with CKD, 63.35% male and 85.71% brown, with an average age of 54.39 years. Of these, 63.97% had between 2 and 10 years of treatment and 57.76% had incomplete primary education. 19.25% resided in Russas. Results: After hemodialysis, the results showed 44 mg/dL of Urea, 48.44% of patients with normal values. Average hemoglobin and hematocrit were 11.8 g/dL and 33.7%, respectively, with 63.35% having reduced values. 85.10% of the patients had normal platelet counts, 72.04% had adequate levels of iron and albumin, 52.79% had high levels of ferritin, 23.61% had reduced transferrin and satisfactory lipid levels. 79.50% had serum levels of potassium within the normal range, 12.42% of phosphorus above normal, 85.09% of calcium within normal values, 39.13% of PTHi normal and 86.33% of glucose within the values considered normal. Based on the results, it was concluded that all patients on hemodialysis have several changes due to CKD and the treatment process itself. Therefore, carrying out tests to assess or monitor possible complications of CRF is essential to create more effective strategies and interventions that improve the care provided to these patients and, consequently, their quality and life expectancy.

La Enfermedad Renal Crónica (ERC) es una reducción importante de la función renal que provoca cambios en el metabolismo de los individuos. Para monitorizar la evolución de la ERC y prevenir posibles complicaciones, se realizó una encuesta para evaluar el perfil sociodemográfico, bioquímico y hematológico de los pacientes con Insuficiencia Renal Crónica (IRC) en hemodiálisis. Esta investigación fue cuantitativa, descriptiva y transversal con carácter retrospectivo, realizada a través del análisis de datos secundarios contenidos en las historias clínicas de los pacientes. La recolección de datos ocurrió en el Centro de Hemodiálisis de la ciudad de Russas, Ceará. La muestra estuvo constituida por 161 pacientes con ERC, 63,35% del sexo masculino y 85,71% pardos, con una edad media de 54,39 años. De estos, 63,97% tenían entre 2 y 10 años de tratamiento y 57,76% tenían primaria incompleta. El 19,25% residía en Russas. Resultados: Posterior a la hemodiálisis los resultados arrojaron 44 mg/dL de Urea, 48,44% de los pacientes con valores normales. La hemoglobina y el hematocrito medios fueron 11,8 g/dl y 33,7 %, respectivamente, con un 63,35 % con valores reducidos. El 85,10% de los pacientes presentaba plaquetas normales, el 72,04% presentaba niveles adecuados de hierro y albúmina, el 52,79% presentaba niveles elevados de ferritina, el 23,61% presentaba transferrina reducida y niveles satisfactorios de lípidos. El 79,50% presentaba niveles séricos de potasio dentro de la normalidad, el 12,42% de fósforo por encima de lo normal, el 85,09% de calcio dentro de los valores normales, el 39,13% de PTHi normal y el 86,33% de glucosa dentro de los valores considerados normales. Con base en los resultados, se concluyó que todos los pacientes en hemodiálisis tienen varios cambios debido a la ERC y al propio proceso de tratamiento. Por tanto, la realización de pruebas para evaluar o monitorizar las posibles complicaciones de la IRC es fundamental para crear estrategias e intervenciones más eficaces que mejoren la atención a estos pacientes y, en consecuencia, su calidad y esperanza de vida.

Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

Marcadores bioquímicos propuestos para el estudio de la sarcopenia / Proposed biochemical markers for the study of sarcopenia

La sarcopenia asociada a la edad es una condición clínica caracterizada por una disminución en la fuerza, calidad y cantidad de masa muscular así como también en la función muscular. Un biomarcador se define como una característica que es medible objetivamente y evaluable como indicador de un proceso biológico normal, patológico o respuesta terapéutica a una intervención farmacológica. Los marcadores bioquímicos propuestos para el estudio de la sarcopenia pueden ser categorizados en dos grupos. El primero de ellos evalúa el estatus musculoesquelético; este panel de marcadores está formado por miostatina/folistatina, procolágeno aminoterminal tipo III e índice de sarcopenia. El segundo grupo de marcadores bioquímicos evalúa factores causales, para lo cual se sugiere medir el factor de crecimiento insulino-símil tipo 1 (IGF-1), dehidroepiandrosterona (DHEAS), cortisol, facto-res inflamatorios [proteína C reactiva (PCR), interleuquina 6 (IL-6) y factor de necrosis tu-moral (TNF-a)]. Las recomendaciones realiza-das están basadas en la evidencia científica disponible en la actualidad y la disponibilidad de la metodología apropiada para cada uno de los biomarcadores. (AU)

Sarcopenia is a progressive and generalized skeletal muscle disorder defined by decrease in the strength, quality and quantity of muscle mass as well as in muscle function. A biomarker is defined as a feature objectively measured and evaluated as an indicator of a normal biologic process, a pathogenic process or a pharmacologic response to therapeutic intervention. The biochemical markers proposed for the study of sarcopenia may be classified in two groups. The first group evaluates the musculoskeletal status, made up by myostatin/follistatin, N-terminal Type III Procollagen and the sarcopenia index. The second evaluates causal factors, where the measurement of the following is suggested: hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate (DHEAS), cortisol, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)]. The recommendations made are based on scientific evidence currently available and the appropriate methodology availability for each biomarker. (AU)

Minimal fresh gas flow sevoflurane anesthesia and postoperative acute kidney injury in on-pump cardiac surgery: a randomized comparative trial

Abstract Background Compound A is generated by sevoflurane when it reacts with carbon dioxide absorbers with strong bases at minimal fresh gas flow (FGF) and is nephrotoxic in animals. No conclusive data has shown increased risk in humans. The aim of this study was to investigate if minimal FGF promotes an increase in the incidence of acute kidney injury (AKI) when compared to high FGF in patients undergoing on-pump cardiac surgery under sevoflurane anesthesia. Methods Two hundred and four adult patients scheduled for on-pump cardiac surgery under sevoflurane anesthesia were randomly allocated to two groups differentiated by FGF: minimal FGF (0.5 L.min−1) or high FGF (2.0 L.min−1). Baseline creatinine measured before surgery was compared daily to values assayed on the first five postoperative days, and 24-hour urinary output was monitored, according to the KDIGO (Kidney Disease Improving Global Outcomes) guideline to define postoperative cardiac surgery-associated acute kidney injury (CSA-AKI). Creatinine measurements were also obtained 20 and 120 days after hospital discharge. Results Postoperative AKI occurred in 55 patients, 26 patients (29.5%) in the minimal FGF group and 29 patients (31.5%) in the high FGF group (p= 0.774). Twenty days after discharge, 11 patients (6.1%) still had CSA-AKI and 120 days after discharge only 2 patients (1.6%) still had CSA-AKI. Conclusions When compared to high FGF, minimal FGF sevoflurane anesthesia during on-pump cardiac surgery is not associated with increased risk of postoperative AKI in this population at high risk for renal injury.

Tasa de filtración glomerular como estimador de la hipertensión en enfermedades renales y cardiovasculares / Glomerular filtration rate as an estimator of renal and cardiovascular diseases such as hypertension

Introducción: Las fórmulas para la estimación de la tasa de filtración glomerular son fundamentales para estimar el curso de enfermedades renales; incluso ha sido de gran ayuda para obtener datos de prevalencia. Las ecuaciones comparadas con otros métodos son una forma económica y rápida para dar una estimación de la función renal. Objetivo: Describir la utilización de diferentes fórmulas para calcular la tasa de filtración glomerular relacionada con la hipertensión arterial y otras patologías renales y cardiovasculares. Metodología: Se realizó la búsqueda de artículos de investigación en bases de datos como PubMed, Science-Direct, Embase y otras, se estableció un tiempo de publicación entre los años 2018-2022 y se seleccionaron 42 artículos científicos relacionados con el tema. Resultados: La hipertensión arterial es una situación que incrementa el riesgo tanto de enfermedad cardiovascular como de deterioro de la función renal, por lo que en los pacientes hipertensos se espera una relación estrecha en la expresión de ambas patologías. Existen factores que alteran los valores de la creatinina sérica como la dieta, el ejercicio, la edad, el género, la masa muscular, enfermedades musculares y medicamentos. El impacto de la hipertensión en la función renal está descrito además de la relación entre el deterioro de la función renal y el incremento del riesgo cardiovascular; es por esto que en los últimos años la estimación de la función renal se ha incorporado como un marcador de morbilidad y mortalidad cardiovascular. Conclusiones: La estimación de la tasa de filtración glomerular es importante en varios contextos clínicos, en especial en aquellos pacientes con enfermedades que afectan la función glomerular, la creatinina es el biomarcador más usado a pesar de sus evidentes limitaciones.

Introduction: Formulas for estimating glomerular fil-tration rate are fundamental for estimating the course of renal diseases; they have even been of great help in obtaining prevalence data. Equations compared with other methods are an economical and fast way to give an estimation of renal function. Objective: Describe the use of different formulas to calculate the glomerular filtration rate related to high blood pressure and other kidney or cardiovascular pa-thologies. Methodology: Research articles were searched in da-tabases such as PubMed, Science-Direct, Embase and others, a publication time was established between the years 2018-2022 and 42 scientific articles related to the topic were selected. Results: Arterial hypertension is a situation that in-creases the risk of both cardiovascular disease and re-nal function deterioration, so in hypertensive patients a close relationship in the expression of both pathologies is expected. There are factors that alter serum creati-nine values such as diet, exercise, age, gender, muscle mass, muscle diseases and medications. The impact of hypertension on renal function has been described in addition to the relationship between the deterioration of renal function and the increase in cardiovascular risk; this is why in recent years the estimation of renal func-tion has been incorporated as a marker of cardiovascu-lar morbidity and mortality. Conclusions: The estimation of glomerular filtration rate is important in several clinical contexts, especia-lly in those patients with diseases that affect glomerular function; creatinine is the most widely used biomarker despite its obvious limitations

Therapeutic mechanism of Shenbing Decoction Ⅲ for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats / 南方医科大学学报

OBJECTIVE@#To observe the effect of Shenbing Decoction Ⅲ for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking.@*METHODS@#Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction Ⅲ group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction Ⅲ against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets.@*RESULTS@#Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction Ⅲ treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction Ⅲ were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction Ⅲ had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction Ⅲ obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue.@*CONCLUSION@#Shenbing Decoction Ⅲ can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1.

Treatment outcome of laparoscopic partial nephrectomy in patients with renal tumors of moderate to high complexity / 北京大学学报(医学版)

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.

Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016 / 中华医学杂志(英文版)

BACKGROUND@#Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States.@*METHODS@#This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes.@*RESULTS@#After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses.@*CONCLUSIONS@#Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.

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 / 中华危重病急救医学

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.

Cistatina C: la necesidad de su conocimiento en la atención preventiva de daño renal / Cystatin c: the need to know it in the preventive care of kidney damage

El conocimiento y actualización sobre la Cistatina C como marcador de daño renal precoz es en extremo necesario para los profesionales de la salud con vistas a mejorar el diagnóstico temprano de enfermedad renal. Las autoras realizaron una revisión bibliográfica actualizada a través de varios estudios científicos, lo que permitió poder informar que aun cuando para la evaluación de la función renal uno de los marcadores sanguíneos convencionales más utilizados es la creatinina, el estudio sanguíneo de Cistatina C no está sometido a diferentes fuentes de variabilidad biológica, ni a factores dependientes del paciente, por lo que sería idóneo tenerlo en cuenta como marcador de función renal precoz.

Knowledge and updating on Cystatin C as a marker of early kidney damage is extremely necessary for health professionals with a view to improving early diagnosis of kidney disease. The authors carried out an updated bibliographical review through various scientific studies, which allowed us to inform that even when for the evaluation of renal function one of the most widely used conventional blood markers is creatinine, the Cystatin C blood study is not subjected to different sources of biological variability, nor to factors dependent on the patient, so it would be ideal to take it into account as a marker of early renal function.

A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD / 生理学报

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Effects of interleukin-4-modified gold nanozymes on the full-thickness skin defects in diabetic mice / 中华烧伤杂志

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.

Applicability of Seven Glomerular Filtration Rate Evaluation Formulas in Dose Adjustment of High Concentration of Methotrexate Chemotherapy in Children with ALL / 中国实验血液学杂志

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.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Clinical Characteristics and Risk Factors for 30-Day Mortality in Patients with Hematologic Diseases Infected by Carbapenem-Resistant Organisms / 中国实验血液学杂志

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.

Mechanism of regulatory T cells in heat stroke-induced acute kidney injury / 中华危重病急救医学

OBJECTIVE@#To investigate the mechanism of regulatory T cells (Treg) in heat stroke (HS)-induced acute kidney injury (AKI).@*METHODS@#Male SPF Balb/c mice were randomly divided into control group, HS group (HS+Rat IgG), HS+PC61 group, and HS+Treg group (n = 6). The HS mice model was established by making the body temperature of the mice reach 42.7 centigrade at room temperature 39.5 centigrade with relative humidity 60% for 1 hour. In HS+PC61 group, 100 μg PC61 antibody (anti-CD25) was injected through the tail vein in consecutive 2 days before the model was established to eliminate Tregs. Mice in HS+Treg group was injected with 1×106 Treg via tail vein immediately after successful modeling. The proportion of Treg infiltrated in the kidney, serum creatinine (SCr) and histopathology, levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) both in the serum and kidney tissue, as well as proportion of neutrophils and macrophages located in the kidney were observed at 24 hours after HS.@*RESULTS@#HS dampened renal function and exaggerated kidney injury, up-regulated levels of inflammatory cytokines both in local kidney and circulation, and increased infiltration of neutrophils and macrophages to the injured kidneys. The proportion of Treg (Treg/CD4+) infiltrated in kidney was significantly decreased in HS group, compared with control group [(3.40±0.46)% vs. (7.67±0.82)%, P < 0.01]. Compared with HS group, local Tregs in kidney were almost completely depleted via PC61 antibody [(0.77±0.12)% vs. (3.40±0.46)%, P < 0.01]. Depletion of Tregs could exacerbate HS-AKI, indicating by increased serum creatinine [SCr (mmol/L): 348.22±35.36 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 4.70±0.20 vs. 3.60±0.20, P < 0.01), incremental levels of IFN-γand TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 747.70±64.52 vs. 508.46±44.79, serum TNF-α (ng/L): 647.41±26.62 vs. 464.53±41.80, both P < 0.01], and more infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (6.63±0.67)% vs. (4.37±0.43)%, macrophage proportion: (38.70±1.66)% vs. (33.19±1.55)%, both P < 0.01]. On the contrast, adoptive transfer of Tregs could reverse the aforementioned effects of Treg depletion, indicating by incremental proportion of Tregs in the injured kidney [(10.58±1.19)% vs. (3.40±0.46)%, P < 0.01], decreased serum creatinine [SCr (mmol/L): 168.24±40.56 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 2.73±0.11 vs. 3.60±0.20, P < 0.01), reduced levels of IFN-γ and TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 262.62±22.68 vs. 508.46±44.79, serum TNF-α (ng/L): 206.41±22.58 vs. 464.53±41.80, both P < 0.01], and less infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (3.04±0.33)% vs. (4.37±0.43)%, macrophage proportion: (25.68±1.93)% vs. (33.19±1.55)%, both P < 0.01].@*CONCLUSIONS@#Treg might be involved in HS-AKI, possibly via down-regulation of pro-inflammatory cytokines and infiltration of inflammatory cells.

Expression of LRG-1 in mice with hypertensive renal damage and its significance / 中南大学学报(医学版)

OBJECTIVES@#Long-term elevated blood pressure may lead to kidney damage, yet the pathogenesis of hypertensive kidney damage is still unclear. This study aims to explore the role and significance of leucine-rich alpha-2-glycoprotein-1 (LRG-1) in hypertensive renal damage through detecting the levels of LRG-1 in the serum and kidney of mice with hypertensive renal damage and its relationship with related indexes.@*METHODS@#C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted.@*RESULTS@#Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1β, and IL-6.@*CONCLUSIONS@#Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage.