Contrast-induced acute kidney injury (CI-AKI) is a major cause of hospital-acquired AKI, but its molecular pathogenesis remains incompletely understood. In this study, we used quantitative 4D proteomics, integrating ion mass-to-charge ratio (m/z), retention time, ion intensity, and ion mobility, to profile renal tissues from a novel rat CI-AKI model based on renal venous congestion and contrast exposure, with sham-operated rats as controls. Differentially expressed proteins were identified and analyzed using pathway enrichment and protein-protein interaction (PPI) network approaches, followed by experimental validation. Using nominal screening criteria (|log2FC| ≥ 1.5 and p < 0.05), we identified 180 candidate differentially expressed proteins, including 92 upregulated and 88 downregulated proteins. Pathway-level analyses showed coordinated upregulation of complement-related proteins, including C3/C5 convertase-related components and terminal pathway proteins, such as C9, together with a C4 isoform annotated as C4a in the reference database. Coagulation and fibrinolysis pathways were also markedly altered, including fibrinogen chains (FGA, FGB, FGG), PLAU, SERPINA1, and SERPINF2. In contrast, proteins associated with AMPK and MAPK signaling (including HNF4α, PRKAA2, PRKAB1, and MAP2K3) were reduced. These pathway-level changes were supported by RT-qPCR and immunohistochemical analyses. Collectively, our findings support a multidimensional injury network in rat CI-AKI involving complement activation, coagulation-fibrinolysis dysregulation, and impaired metabolic/stress-response signaling, and provide a proteomic resource for future mechanistic and translational studies.

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K+ and Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

Background: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis. Methods: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10. Results: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells. Conclusions: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.

Introduction Severe pneumonia is a crucial issue in the development of acute kidney injury (AKI). This study evaluated the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of severe pneumonia-associated AKI.Methods In this real-world retrospective cohort study, we recruited 180 patients with severe pneumonia who were hospitalized and received GDRRT in a third-class general hospital in East China between January 1, 2017, and December 31, 2021. Clinical data on baseline characteristics, biochemical indicators, and renal replacement therapy were collected. Patients were divided into Early and Late RRT groups according to fluid status, inflammation progression, and pulmonary radiology. We investigated in-hospital all-cause mortality (primary endpoint) and renal recovery (secondary endpoint) between the two groups.Results Among the 154 recruited patients, 80 and 74 were in the early and late RRT groups, respectively. There were no significant differences in the demographic characteristics between the two groups. The duration of admission to RRT initiation was significantly shorter in Early RRT group [2.5(1.0, 8.7) d vs. 5.0(1.5,13.5) d, p = 0.027]. At RRT initiation, the patients in the Early RRT group displayed a lower percentage of fluid overload, lower doses of vasoactive agents, higher CRP levels, and higher rates of radiographic progression than those in the Late RRT group. The all-cause in-hospital mortality was significantly lower in the Early RRT group than in Late group (52.5% vs. 86.5%, p < 0.001). Patients in the Early RRT group displayed a significantly higher proportion of complete renal recovery at discharge (40.0% vs. 8.1%, p < 0.001).Conclusion This study clarified that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status and inflammation progression, was associated with reduced hospital mortality and better recovery of renal function. Our preliminary study suggests that early initiation of RRT may be an effective approach for severe pneumonia-associated AKI.

BACKGROUND:The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.RESULTS:Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.CONCLUSION:This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

Background Cardiac surgery-associated acute kidney injury (AKI) is one of the common complications of cardiac surgery. Preoperative angiography helps assess heart disease but may increase the risk of AKI. Although more and more patients with preoperative renal dysfunction can undergo cardiac surgery with the advances in surgical techniques, there is little research on the effect of angiography on postoperative AKI in these patients. This study investigates whether angiography increases the risk of AKI after cardiac surgery in patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m 2 ). Methods Patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m 2 ) who underwent angiography and cardiac surgery successively from January 2015 to December 2020 were retrospectively enrolled in this study. The primary outcome was postoperative AKI, defined as the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate analysis and multivariate regression were performed to identify the association between angiography timing and AKI. Results A total of 888 consecutive eligible patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m 2 ) were enrolled in this study. The incidence of AKI was 48.31%. Male (OR = 1.903), the interval between angiography and surgery (0-2d OR = 2.161; 3-6d OR = 3.291), cross-clamp duration (OR = 1.009), were identified as predictors for AKI. The interval between angiography and surgery was also associated with AKI in the patients with 15 ≤ eGFR < 30ml/min/1.73m 2 (0-2d OR = 4.826; 3-6d OR = 5.252), 30 ≤ eGFR < 45 ml/min/1.73m 2 (0-2d OR = 2.952; 3-6d OR = 3.677), but not associated with AKI in patients with 45 ≤ eGFR < 60 ml/min/1.73m 2 . Conclusions In patients with preoperative renal dysfunction, the interval between angiography and cardiac surgery (0-2d and 3-6d) was associated with AKI. For patients with poorer preoperative renal function, the interval between angiography and cardiac surgery is of great concern.

ABSTRACT:Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. After the exploratory testing phase, we successfully constructed a CI-AKI rat model by inducing renal congestion by clamping the unilateral renal vein, removing the contralateral kidney, and a single tail vein injection of iohexol. This novel CI-AKI rat model showed elevated serum creatinine, urea nitrogen, and released tubular injury biomarkers (KIM-1 and NGAL), reduced glomerular filtration rate, and typical pathologic features of CM-induced tubular injury with extensive foamy degeneration, tubular edema, and necrosis. Electron microscopy and confocal laser scanning revealed excessive mitochondrial fission and increased translocation of Drp1 from the cytoplasm to the mitochondrial surface in tubular epithelial cells. As a Drp1 inhibitor, Mdivi-1 attenuated excessive mitochondrial fission and exerted reno-protection against CM injury. Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.

TWIK-related acid-sensitive K+ channel-2 (TASK-2, encoded by Kcnk5) is essential in cell biological processes, by regulating transmembrane K+ balance. In the present study, we aimed to clarify the role of TASK-2 in renal fibrosis and explore the underlying mechanism. We found that TASK-2 level was elevated in the renal tubular UUO- and UIR-induced renal fibrosis as well as in patients with renal tubulointerstitial fibrosis. Knockout of Kcnk5 or inhibition of TASK-2 in renal tubules attenuated G2/M cell-cycle arrest and alleviated renal fibrosis. Mechanistically, demethylase fat mass and obesity-associated protein (FTO) reduced N6-adenosine methylation (m6A) of Kcnk5 mRNA following renal fibrosis. FTO deficiency attenuated the upregulation of TASK-2 and renal fibrosis. The results demonstrated the crucial role of TASK-2 in renal fibrosis, which is conducive to a better understanding of the pathogenesis of renal fibrosis. TASK-2 may be a potential treatment strategy to alleviate the development of renal fibrosis.

探究胰岛素联合5-氟尿嘧啶调控Survivin基因信号通路对绒癌细胞化疗增效作用机制研究.将在ATCC细胞库购买的JEG-3细胞(人绒癌细胞)分为空白对照组(B组);胰岛素组(Ⅰ组);5-氟尿嘧啶组(F组);胰岛素联合5-氟尿嘧啶组(IF组).通过Hoechst 33258荧光染色法检测JFEG-3细胞凋亡情况,qRT-PCR法检测Survivin mRNA表达量,克隆法检测JEG-3细胞增殖情况,Western blot法检测Survivin蛋白含量,MTT法检测JEG-3细胞活性的差异性进行实验探究.随着时间的推移,F组、IF组JEG-3细胞的活性显著降低,48 h时,IF组JEG-3细胞的活性最低,I组JEG-3细胞的活性显著升高;与F组、B组、I组相比较,IF组细胞活性下降趋势明显(P＜0.05).F组细胞的细胞核出现核固缩的概率显著高于I组(P＜0.05),与F组相比较,IF组细胞凋亡数量显著升高(P＜0.05).与I组相比较,B组细胞增殖数量显著下降(P＜0.05);与B组相比较,F组细胞增殖数量显著下降(P＜0.05);与F组相比较,IF组细胞增殖数量明显降低(P＜0.05).与I组相比较,B组细胞Survivin蛋白表达、Survivin mRNA表达量显著下降(P＜0.05);与B组相比较,F组细胞Survivin蛋白表达、Survivin mRNA表达量显著下降(P＜0.05);与F组相比较,IF组细胞Survivin蛋白表达、Survivin mRNA表达量显著下降(P＜0.05).胰岛素可能通过协同减少Survivin基因的表达来增强5-FU对绒癌JEG-3细胞的抗肿瘤作用.

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery and the prognosis of AKI worsens with the increase in AKI severity. Syndecan-1(SDC-1) is a biomarker of endothelial glycocalyx degradation. Fluid overload (FO) is associated with poor outcomes in AKI patients and may be related to the damage of endothelial function. This study aimed at demonstrating the association between elevated SDC-1, FO, and AKI progression. Methods: In this prospective study, we screened patients who underwent cardiac surgery and enrolled patients who experienced an AKI within 48 h after surgery from December 1, 2018 to January 31, 2019. Blood and urine samples were collected at the time of AKI diagnosis for plasma SDC-1 (pSDC-1) and urine SDC-1 (uSDC-1) measurements. Fluid balance (FB) = accumulated [fluid intake (L) - fluid output (L)]/body weight (kg) × 100%. FO was defined as FB > 5%. The primary endpoint was progressive AKI, defined as AKI progression from a lower to a higher stage. The patients were divided into progressive AKI group vs. non-progressive AKI group. Results: The quartiles of pSDC-1 concentration (117.3 [67.4, 242.3] ng/mL) showed a graded association with the incidence of progressive AKI, ranging from 5.0, 11.9, 32.6 to 52.4% ( p for trend < 0.001). Multivariate logistic regression showed that increased pSDC-1 was an independent risk factor for progressive AKI. The AUC-ROC area of pSDC-1 concentration in predicting AKI progression was 0.847. Linear regression showed a positive correlation between FB and pSDC-1 concentration ( R 2 = 0.384, p < 0.001). In patients with FO, the progressive AKI incidence was significantly higher in the high pSDC-1 (≥117.3 ng/mL) subgroup than in the low pSDC-1 subgroup (58.3 vs. 17.6%, OR = 9.167, P = 0.005). In patients without FO, the progressive AKI incidence was also significantly higher in the high pSDC-1 subgroup with a lower odds ratio (30.4 vs. 7.4%, OR = 6.714, P = 0.002). Conclusion: Elevated pSDC-1 concentration was associated with progressive AKI after cardiac surgery and showed good predictive ability for progressive AKI. FB was related to the increase of pSDC-1. The interaction between pSDC-1 and FB may further aggravate the progression of AKI.

Objective: To analyze the rationale and evaluate the validity of spot urinary chloride or derived formulas to predict high sodium intake in patients with chronic kidney disease (CKD). Methods: We collected consecutive CKD patients at stages 1-4 who were admitted to our Nephrology department in a single center from January 01, 2014, to December 31, 2017, and tested spot and 24-hour urinary analysis on the same day. The feasibility of urinary chloride to predict urinary sodium was firstly analyzed by calculating their correlations. The validity of predicting excessive sodium intake by spot urinary sodium and chloride, two derived formulas based on spot urinary sodium or chloride, and our previous "CKDSALT" equation were accessed. We finally conducted Receiver operating characteristic (ROC) curves to compare their performance in detecting high sodium intake. Results: All 5204 patients were eventually analyzed. In the derivation cohort (n = 24-47), a strong positive linear correlation existed between urinary sodium and chloride in both spot urine (R-2 = 0.804) and 24-hour urine samples (R-2 = 0.905), and two predictive equations based on spot urinary sodium or chloride were derived. In the validation cohort (n = 2757), spot urinary sodium and chloride only showed "fair" performance. However, both urinary sodium and chloride equations had a "good" performance in ICC, Pearson's correlation, Bland-Altman plots, and ROC curves, while and CKDSALT equation showed the best performance. Conclusions: Spot urinary chloride is a feasible method to predict and monitor high sodium intake in CKD patients, while a novel derived formula could elevate its diagnostic accuracy. (C) 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Podocytes are known to play a determining role in the progression of proteinuric kidney disease. N 6 -methyladenosine (m6A), as the most abundant chemical modification in eukaryotic mRNA, has been reported to participate in various pathological processes. However, its role in podocyte injury remains unclear. In this study, we observed the elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin (ADR) and diabetic nephropathy. METTL14 was also evidently increased in renal biopsy samples from patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy and in cultured human podocytes with ADR or advanced glycation end product (AGE) treatment in vitro. Functionally, we generated mice with podocyte-specific METTL14 deletion, and identified METTL14 knockout in podocytes improved glomerular function and alleviated podocyte injury, characterized by activation of autophagy and inhibition of apoptosis and inflammation, in mice with ADR nephropathy. Similar to the results in vivo, knockdown of METTL14 facilitated autophagy and alleviated apoptosis and inflammation in podocytes under ADR or AGE condition in vitro. Mechanically, we identified METTL14 knockdown upregulated the level of Sirt1, a well-known protective deacetylase in proteinuric kidney diseases, in podocytes with ADR or AGE treatment. The results of MeRIP-qPCR and dual-luciferase reporter assay indicated METTL14 promoted Sirt1 mRNA m6A modification and degradation in injured podocytes. Our findings suggest METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of Sirt1 mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.

Choriocarcinoma (CC) is a gestational trophoblastic tumor secondary to a gravid or non-gravid pregnancy. It is characterized by rapid growth, high invasion, and high metastatic potential and chemotherapy resistance that significantly affect survival rate of CC patients. Insulin is implicated in alleviation of chemotherapy resistance in CC. However, the mechanism of reversing resistance in CC has not been explored. Our purpose was to explore insulin effect on 5-fluorouracil (5-FU) resistance in CC and elucidate its potential mechanism in vitro and in vivo. CKK-8, colony formation, Transwell, and flow cytometry were used to detect the effect of insulin on 5-FU resistance in CC cells JEG-3 and JARS. Xenograft mice were used to evaluate the effect of insulin on 5-FU resistance. Results showed that insulin combined with 5-FU suppressed cell viability by 30% in JEG-3 and 43% in JAR compared with 5-FU alone in 72 h. What's more, insulin combined with 5-FU promoted cell apoptosis, inhibited cell proliferation, migration, and phosphorylation of survivin at residue threonine 34 (Thr34) and drug resistance-related proteins, P-GP and MRP1 levels (p < 0.05). In vivo experiment showed Insulin combined with 5-FU suppressed tumor volume by 35% compared with 5-FU alone and 73% compared with control in CC xenograft mice. In summary, the findings of this study show that insulin reversed chemoresistance of CC cells to 5-FU by inhibiting phosphorylation of survivin. Development of a therapeutic strategy that combines insulin with the chemotherapeutic agent 5-FU has a great potential in improving survival of CC patients.

Background This study attempts to establish a Bayesian networks (BNs) based model for inferring the risk of AKI in gastrointestinal cancer (GI) patients, and to compare its predictive capacity with other machine learning (ML) models. Methods From 1 October 2014 to 30 September 2015, we recruited 6495 inpatients with GI cancers in a tertiary hospital in eastern China. Data on demographics, clinical and laboratory indicators were retrospectively extracted from the electronic medical record system. Predictors of AKI were selected in gLASSO regression, and further incorporated into BNs analysis. Results The incidences of AKI in patients with esophagus, stomach, and intestine cancer were 20.5%, 13.9%, and 12.5%, respectively. Through gLASSO, 11 predictors were screened out, including diabetes, cancer category, anti-tumor treatment, ALT, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (SUA), hypoalbuminemia, anemia, abnormal sodium, and potassium. BNs model revealed that cancer category, treatment, eGFR, and hypoalbuminemia had direct connections with AKI. Diabetes and SUA were indirectly linked to AKI through eGFR, and anemia created connections with AKI through affecting album level. Compared with other ML models, BNs model maintained a higher AUC value in both the internal and external validation (AUC: 0.823/0.790). Conclusion BNs model not only delineates the qualitative and quantitative relationship between AKI and its associated factors but shows the more robust generalizability in AKI prediction.

Background: Fluid overload is related to the development and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI). The study is to investigate the influence of serum creatinine (SCr) corrected by fluid balance on the prognosis of patients with cardiac surgery. Methods: A retrospective study was conducted in 1334 patients who underwent elective cardiac surgery from January 1 to December 31, 2015. Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI were applied to identify CSA-AKI. SCr was measured every 24 hours during ICU period and was accordingly adjusted for cumulative fluid balance. Change in SCr, defined as ∆Crea, was determined by difference between before and after adjustment for cumulative fluid balance. All patients were divided as three groups: underestimation group (∆Crea ≥ P 75 ), normal group (P 25 < ∆Crea < P 75 ) and overestimation group (∆Crea ≤ P 25 ). Results: The incidence of AKI increased from 29.5% to 31.8% after adjustment for fluid balance. Patients in underestimation group showed prolonged length of ICU stay compared with normal group and overestimation group (3.2[1.0-3.0] vs 2.1[1.0-3.0] d, P < 0.001; 3.2[1.0-3.0] vs 2.3[1.0-3.0] d, P < 0.001). Length of hospital stay and mechanical ventilation dependent days in underestimation group were significantly longer than normal group ( P < 0.001). Multivariate analysis showed age, baseline SCr and left ventricular ejection fraction were independently associated with underestimation of creatinine. Conclusions: Cumulative fluid balance after cardiac surgery disturbs accurate measurement of serum creatinine. Patients with underestimation of SCr were associated with poor prognosis.

目的 利用套索(least absolute shrinkage and selection operator,LASSO)回归和贝叶斯网络分析方法 ,构建适合肿瘤患者急性肾损伤(acute kidney injury,AKI)发病风险的贝叶斯网络预测模型,为早期识别高危人群,制定AKI精准预防策略提供科学依据.方法 以2014年10月1日至2015年9月30日在复旦大学附属中山医院就诊的恶性肿瘤住院患者为研究对象.于医院数据管理平台收集患者年龄、性别、体重指数、既往病史、肿瘤类型/治疗、基础肝肾功能、生化和电解质指标等数据资料.通过LASSO回归筛选出与AKI发生显著相关的影响因素;借助贝叶斯网络分析进一步描述变量间相互作用并评价模型预测效能.结果 26914名研究对象中,AKI发病率为12.4％(n=3326),其中肾癌(27.3％),多发性骨髓瘤(24.1％)和急性粒细胞白血病(23.9％)患者的AKI发病率最高.LASSO回归筛选出22个与AKI发生相关性最显著的变量,包括年龄、性别、体重指数、糖尿病史、肿瘤类型/分期/治疗方式、肝功能、肾小球滤过率(estimated glomerular filtration rate,eGFR)/血清肌酐值/血尿酸、白蛋白、血红蛋白和白细胞计数、血钠/血钾等电解质.贝叶斯网络模型发现血红蛋白、eGFR、血氯和血磷与AKI的发生有直接联系;节点治疗方式通过影响血钠和白蛋白等中间节点间接影响AKI的发生;糖尿病和性别通过节点尿酸间接相连eGFR,而后者是AKI的父节点.模型推理在其他条件一致的情况下,贫血和eGFR≤59 mL·min-1·1.73 m-2的患者发生AKI的概率最高(55.7％);而上述指标均正常者AKI发病率最低(3.0％).模型评价发现贝叶斯网络模型的分类准确率为88.8％,接受者操作特性曲线曲线下面积为0.806.结论 基于LASSO变量选择联合贝叶斯网络分析构建的模型在肿瘤相关AKI的影响因素分析中更符合实际理论,其在发病风险预测中有较好的临床应用价值.

Background Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. Methods Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. Results We recruited 252 patients and divided them into a high-TMAO group (>4.73 μg/mL) and a low-TMAO group (≤4.73 μg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). Conclusions High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Background This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.