1.Invasiveness assessment by CT quantitative and qualitative features of lung cancers manifesting ground-glass nodules in 555 patients: A retrospective cohort study
Yantao YANG ; Wei WANG ; Yichen YANG ; Biying WANG ; Huilian HU ; Ziqi JIANG ; Dezhong CAI ; Yaowu DUAN ; Jiezhi JIANG ; Jia LUO ; Guangqiang ZHAO ; Yunchao HUANG ; Lianhua YE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):51-58
Objective To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.
2.Relationship between preoperative serum bilirubin concentration and postoperative delirium in patients undergoing knee or hip replacement
Shuhui HUA ; Mengya ZHANG ; Shanling XU ; Yunchao YANG ; Haoran ZHANG ; Chuan LI ; Yanan LIN ; Rui DONG ; Hongyan GONG ; Xu LIN ; Yanlin BI ; Bin WANG
Chinese Journal of Anesthesiology 2024;44(3):286-291
Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.
3.Effect of Xuanfei Zhisou Prescription on IL-17 Signaling Pathway in COPD Model Rats
Yanli SHI ; Yunchao WANG ; Zhen YANG ; Xinhua WANG ; Zhiyong JIA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):28-39
ObjectiveTo investigate the effect of Xuanfei Zhisou prescription on the interleukin-17 (IL-17) signaling pathway in model rats with chronic obstructive pulmonary disease (COPD). MethodA total of 60 Wistar rats were randomly divided into a blank group (10 rats) and a model group (50 rats), and COPD model rats were established by tracheal infusion of lipopolysaccharide combined with passive fumigation. After modeling, the rats were divided into the model group, dexamethasone group, and high, medium, and low-dose Xuanfei Zhisou prescription groups (3.6, 1.8, 0.9 g·kg-1·d-1) according to the random number table. Rats in the blank group and model group were given normal saline of 10 mL·kg-1·d-1 by gavage administration, and the intervention groups of Xuanfei Zhisou prescription were given corresponding drugs. Rats in the dexamethasone group were given dexamethasone of 2.57×10-4 g·kg-1·d-1 for 28 days. The level of pulmonary function indexes in rats was measured by a pulmonary function detector. The contents of interleukin-6 (IL-6), interleukin-8 (IL-8), IL-17, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The positive expressions of IL-17A, IL-17RA, nuclear factor-κB activator 1 (Act1), tumor necrosis factor-associated factor 6 (TRAF6), p-p38 mitogen-activated protein kinase (p-p38 MAPK), nuclear factor-κB p65 (NF-κB p65), and phosphorylation were detected by immunohistochemistry (IHC). The protein expression levels of IL-17A, IL-17RA, Act1, and TRAF6 in the lung tissue were detected by Western blot. The mRNA expressions of IL-17A, IL-17RA, Act1, and TRAF6 in the lung tissue were detected by Real-time polymerase chain reaction (Real-time PCR). ResultCompared with the blank group, the serum contents of IL-6, IL-8, IL-17, IL-1β, and TNF-α in the model group were significantly increased (P<0.05), and the flow rate and volume indexes of pulmonary function in the model group were significantly decreased (P<0.05), while the time indexes and other indexes were significantly increased (P<0.05). The mRNA and protein expression levels of IL-17A, IL-17RA, Act1, and TRAF6 in pulmonary tissue and the positive expressions of downstream NF-κB p65, p-NF-κB p65, and p-p38 MAPK were increased (P<0.05). Compared with the model group, the levels of IL-6, IL-8, IL-17, IL-1β, and TNF-α in the serum of all treatment groups were decreased to varying degrees (P<0.05), and the indexes of pulmonary function were improved to different degrees (P<0.05). The mRNA and protein levels of IL-17A, IL-17RA, Act1, and TRAF6 and the positive expression of downstream NF-κB p65, p-NF-κB p65, and p-p38 MAPK in high and medium-dose Xuanfei Zhisou prescription groups were significantly decreased (P<0.05). ConclusionXuanfei Zhisou prescription can effectively resist inflammation of COPD rats. The mechanism may be related to down-regulating the protein expression of IL-17A, IL-17RA, Act1, and TRAF6, inhibiting downstream NF-κB and p38 MAPK signaling pathways, and reducing the release of IL-6, IL-8, TNF-α, IL-17, and IL-1β, thus reducing the airway inflammation response.
4.The impact of long-term dexamethasone administration on diaphragmatic atrophy in rats with acute respiratory distress syndrome
Qianqian WANG ; Peng SHEN ; Haitao TIAN ; Xiaoping ZHANG ; Yunchao SHI ; Jiangang ZHU ; Maoxian YANG ; Longsheng XU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(2):145-150
Objective To investigate the impact of dexamethasone(DEX)on diaphragmatic atrophy caused by acute respiratory distress syndrome(ARDS)and its correlation with diaphragmatic protein metabolism.Methods Twenty healthy male Sprague-Dawley(SD)rats were randomly assigned to control,ARDS model,low-dose DEX,and high-dose DEX group,with each group consisting of five rats.ARDS was induced in the rats by intratracheal administration of lipopolysaccharide(LPS)at 4 mg/kg.Conversely,intratracheal saline was administered to the control group at 2 mL/kg.Following the induction of the model,an intraperitoneal injection of DEX at 1 mg·kg-1·d-1 was administered to the low-dose DEX group.Conversely,DEX at 5 mg·kg-1·d-1 was administered to the high-dose group for 7 consecutive days.Subsequently,on the eighth day of the experiment,the diaphragmatic weight of all rats was measured.Real-time quantitative polymerase chain reaction(PCR)was utilized to assess the mRNA expression of interleukins(IL-1β,IL-18)in each group.Western blotting was employed to determine the protein expression levels of nuclear factor-κB(NF-κB)p65,NOD-like receptor protein 3(NLRP3),caspase-1,Gasdermin D(GSDMD),myosin heavy chain 2(Myh2),and F-box protein 32(Fbxo32).Additionally,immunohistochemistry was utilized to evaluate the ratio of fast to slow muscle fibers in the diaphragm.Results The ARDS model group showed significant reductions in body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression compared to the control group[body weight(g):266±17 vs.292±15,diaphragm weight(g):0.77±0.02 vs.0.92±0.08,fast muscle fibers:(74±1)%vs.(78±3)%,Myh2 protein expression(Avalue):0.75±0.07 vs.0.95±0.05,all P<0.05].Conversely,significant increases were observed in the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32[IL-1β mRNA(IL-1β/GAPDH):2.2±0.3 vs.1.0±0.2,IL-18 mRNA(IL-18/GAPDH):2.3±0.3 vs.1.0±0.3,slow muscle fibers:(26±1)%vs.(22±3)%,NF-κB p65 protein expression(A value):0.40±0.15 vs.0.17±0.05,NLRP3 protein expression(A value):0.51±0.05 vs.0.27±0.08,caspase-1 protein expression(A value):0.54±0.12 vs.0.30±0.19,GSDMD protein expression(A value):0.40±0.12 vs.0.20±0.05,Fbxo32 protein expression(A value):0.51±0.15 vs.0.33±0.08,all P<0.05].Compared with the ARDS group,both low and high doses of DEX were found to further reduce body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression,and further increase the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32,with the changes in the high dose DEX group being more significant than those in the low dose group[body weight(g):198±14 vs.222±16,diaphragm weight(g):0.57±0.04 vs.0.68±0.04,fast muscle fibers:(56±5)%vs.(69±2)%,Myh2 protein expression(A value):0.29±0.16 vs.0.57±0.15,IL-1βmRNA expression:5.6±1.4 vs.3.3±0.6,IL-18 mRNA expression(IL-18/GAPDH):5.8±1.2 vs.3.9±0.6,slow muscle fibers:(44±5)%vs.(31±2)%,NF-κB p65 protein expression(A value):0.87±0.04 vs.0.70±0.07,NLRP3 protein expression(A value):0.75±0.08 vs.0.63±0.04,caspase-1 protein expression(A value):0.99±0.06 vs.0.82±0.08,GSDMD protein expression(Avalue):0.85±0.11 vs.0.61±0.10,Fbxo32 protein expression(Avalue):1.00±0.10 vs.0.78±0.12,all P<0.05].Normal muscle fiber structure was revealed by microscopic observation in the control group,clear fiber separation in the ARDS model group,and disordered muscle fiber arrangement with structural distortion was noted in both low and high-dose DEX groups.Conclusion Prolonged administration of DEX may worsen diaphragmatic atrophy induced by ARDS,possibly by promoting the activation of the NLRP3 inflammasome and cell pyroptosis.
5.Analysis of Clinical Epidemiological Characteristics of 15,967 Lung Cancer Surgery Patients in Yunnan Cancer Hospital from 2013 to 2022.
Ruke TANG ; Yujie LEI ; Lianhua YE ; Guangqiang ZHAO ; Xudong XIANG ; Gaofeng LI ; Guangjian LI ; Xi WANG ; Ying CHEN ; Kaiyun YANG ; Xiaobo CHEN ; Jiapeng YANG ; Min ZHAO ; Bingquan XIANG ; Qiubo HUANG ; Guangcan LUO ; Hongwei ZHANG ; Yunchao HUANG
Chinese Journal of Lung Cancer 2024;27(12):911-918
BACKGROUND:
Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer.
METHODS:
Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics.
RESULTS:
Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%).
CONCLUSIONS
The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over the past decade.
Humans
;
Female
;
Male
;
Lung Neoplasms/pathology*
;
Middle Aged
;
China/epidemiology*
;
Aged
;
Adult
;
Aged, 80 and over
6.Relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium
Haoran ZHANG ; Yihan CHEN ; Xu LIN ; Bin WANG ; Yunchao YANG ; Yanlin BI
Chinese Journal of Anesthesiology 2023;43(5):526-530
Objective:To evaluate the relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium(POD) in the patients.Methods:A total of 938 participants of either sex, aged 50-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists Physical Status classificationⅠorⅡ, with preoperative Mini-Mental State Examination score ≥24, without communication barriers, undergoing elective knee or hip joint replacement under combined spinal-epidural anesthesia from June 2020 to June 2022 in Qingdao Municipal Hospital, were enrolled. The vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was recorded. The cerebrospinal fluid 2 ml was extracted after the puncture needle was successfully inserted into the subarachnoid space for determination of the concentrations of Aβ42, total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay (by enzyme-linked immunosorbent assay). The Aβ42/t-tau and Aβ42/p-tau ratios were calculated. POD was assessed using the Confusion Assessment Method twice a day within 7 days after surgery or before discharge.The patients were divided into POD group and non-POD group according to whether they developed POD. The risk factors of which P values were less than 0.20 in the univariate logistic regression would enter the multivariate logistic regression analysis to investigate the relationship between SARS-CoV-2 vaccine and level of cerebral spinal fluid (CSF) biomarkers and POD. Results:Eight hundred and seventy-four patients were finally enrolled in the analysis, of which 169 patients developed POD, with an incidence of 19.3%.The results of logistic regression showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation, preoperative concentrations of Aβ42 in CSF, and increase in Aβ42/t-tau and Aβ42/p-tau ratios were protective factors for POD, and preoperative elevated concentrations of t-tau and p-tau in CSF were risk factors for POD ( P<0.05). After gender, age, preoperative Mini-Mental State Examination score, years of education, history of drinking, hypertension, diabetes mellitus and coronary heart disease were added to eliminate the influence of confounding factors, the results still showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was a protective factor for POD. Conclusions:Vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation is a protective factor for POD in patients.
7.Relationship between preoperative estimated glomerular filtration rate and postoperative delirium
Yunchao YANG ; Qian LIU ; Haoran ZHANG ; Xu LIN ; Bin WANG ; Yanlin BI
Chinese Journal of Anesthesiology 2023;43(6):676-681
Objective:To evaluate the relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative delirium (POD) in the patients.Methods:Six hundred and twenty-five patients, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia, were included. Peripheral blood samples were collected before surgery, and serum creatinine levels were measured by the sarcosine oxidase method, and eGFR was calculated using the MDRD equation. After successful spinal-epidural puncture, cerebrospinal fluid 2 ml was collected for determination of β-amyloid 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group (NPOD group) according to the occurrence of POD. The logistic regression analysis was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic (ROC) curve was drawn to evaluate the accuracy of eGFR and biomarkers in predicting POD.Results:A total of 514 patients were finally enrolled in this study, and the incidence of POD was 16.7%. The logistic regression analysis showed that decreased eGFR and increased levels of P-tau and T-tau in CSF were risk factors for POD, while increased CSF Aβ42 level, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD after adjusting for multiple confounding variables ( P<0.05). Analysis of mediating effet: The direct effect of eGFR on POD was -0.0 005 267, the total effect was 0.0 046 446, T-tau had a partly mediating role and the mediating effect accounted for 11.3% of the total effect. The area under the ROC curve of eGFR and CSF biomarker in predicting POD was 0.812( P<0.001). Conclusions:Preoperative decrease in eGFR is a risk factor for POD, and T-tau in CSF serves as a key mediator in the relationship between eGFR and POD.
8.Relationship between preoperative serum albumin concentrations and postoperative delirium in patients undergoing total knee/hip arthroplasty
Bin WANG ; Xiao WANG ; Haoran ZHANG ; Yunchao YANG ; Xinhui TANG ; Fei WANG ; Jiahan WANG ; Xu LIN ; Yanlin BI
Chinese Journal of Anesthesiology 2023;43(7):781-786
Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.
9.Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress.
Maoxian YANG ; Haitao TIAN ; Peng SHEN ; Longsheng XU ; He LIU ; Jian'gang ZHU ; Qianqian WANG ; Yunchao SHI
Chinese Critical Care Medicine 2023;35(4):393-397
OBJECTIVE:
To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS).
METHODS:
A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope.
RESULTS:
Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05).
CONCLUSIONS
Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.
Male
;
Rats
;
Animals
;
Rats, Sprague-Dawley
;
NF-kappa B
;
Actins
;
Caspase 3
;
Curcumin
;
Lipocalin-2
;
Toll-Like Receptor 4
;
Inflammasomes
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
Reactive Oxygen Species
;
Saline Solution
;
Kidney
;
Superoxide Dismutase
10.Relationship between preoperative serum cystatin C concentration and postoperative delirium
Yunchao YANG ; Weichen LI ; Haoran ZHANG ; Xu LIN ; Bin WANG ; Yanlin BI
Chinese Journal of Anesthesiology 2023;43(8):916-920
Objective:To evaluate the relationship between preoperative serum cystatin C (Cys C) concentration and postoperative delirium (POD) in the patients.Methods:Three hundred and ninety patients, aged >50 yr, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective knee and hip replacement under combined spinal-epidural anesthesia, with Mini-Mental State Examination scores >23 at 1 day before operation, were included in the study. Peripheral blood samples were collected before operation, and the serum Cys C concentration was measured by the latex-enhanced immunoturbidimetric assay. The cerebrospinal fluid (CSF) 2 ml was collected after successful spinal-epidural puncture for determination of amyloid-β 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) concentrations by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group according to whether POD occurred. The logistic regression analysis was used to identify the risk and protective factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic curve was drawn to evaluate the accuracy of serum Cys C concentration and combination of serum Cys C conceatration and CSF biomarker concentration in predicting POD.Results:Three hundred and twenty-seven patients were finally enrolled, and the incidence of POD was 13.5%. The results of logistic regression showed that increased serum Cys C concentration and increased concentrations of P-tau and T-tau in CSF were risk factors for POD, while increased concentration of Aβ42 and increased Aβ42/P-tau ratio and Aβ42/T-tau ratio in CSF were protective factors for POD ( P<0.05) after adjusting for multiple confounding variables such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history. The mediation analysis showed that the relationship between serum Cys C concentration and POD was mediated by T-tau concentration in CSF (11.1%) and by Aβ42/T-tau ratio in CSF (18.0%). The area under the receiver operating characteristic curve of serum Cys C and CSF biomarker concentrations in predicting POD was 0.807 ( P<0.001). Conclusions:Increase in preoperative serum Cys C concentration is a risk factor for POD. T-tau concentration and Aβ42/T-tau ratio in CSF serve as the key mediators in the relationship between preoperative serum Cys C concentration and POD.

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