Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed that the MyD88/p38 MAPK pathway plays key roles in mediating subsequent inflammation and apoptosis signaling activation. Treatment with tauroursodeoxycholic acid, a chemical chaperone drug that functions as an endoplasmic reticulum stress inhibitor, effectively suppressed endoplasmic reticulum stress, promoted secretion of the α3 chains, and inhibited the activation of the MyD88/p38 MAPK pathway. Tauroursodeoxycholic acid treatment significantly improved kidney function in vivo. These results partly clarified the pathogenesis of kidney injuries associated with Alport syndrome, especially in glomeruli, and suggested that tauroursodeoxycholic acid might be useful for the early clinical treatment of Alport syndrome.

Multi-Selenophene Incorporated Thiazole Imide-Based n-Type Polymers for High-Performance Organic Thermoelectrics.

Developing polymers with high electrical conductivity (σ) after n-doping is a great challenge for the advance of the field of organic thermoelectrics (OTEs). Herein, we report a series of thiazole imide-based n-type polymers by gradually increasing selenophene content in polymeric backbone. Thanks to the strong intramolecular noncovalent N⋅⋅⋅S interaction and enhanced intermolecular Se⋅⋅⋅Se interaction, with the increase of selenophene content, the polymers show gradually lowered LUMOs, more planar backbone, and improved film crystallinity versus the selenophene-free analogue. Consequently, polymer PDTzSI-Se with the highest selenophene content achieves a champion σ of 164.0 S cm-1 and a power factor of 49.0 µW m-1 K-2 in the series when applied in OTEs after n-doping. The σ value is the highest one for n-type donor-acceptor OTE materials reported to date. Our work indicates that selenophene substitution is a powerful strategy for developing high-performance n-type OTE materials and selenophene incorporated thiazole imides offer an excellent platform in enabling n-type polymers with high backbone coplanarity, deep-lying LUMO and enhanced mobility/conductivity.

Cyano-Functionalized Pyrazine: A Structurally Simple and Easily Accessible Electron-Deficient Building Block for n-Type Organic Thermoelectric Polymers.

Developing low-cost and high-performance n-type polymer semiconductors is essential to accelerate the application of organic thermoelectrics (OTEs). To achieve this objective, it is critical to design strong electron-deficient building blocks with simple structure and easy synthesis, which are essential for the development of n-type polymer semiconductors. Herein, we synthesized two cyano-functionalized highly electron-deficient building blocks, namely 3,6-dibromopyrazine-2-carbonitrile (CNPz) and 3,6-Dibromopyrazine-2,5-dicarbonitrile (DCNPz), which feature simple structures and facile synthesis. CNPz and DCNPz can be obtained via only one-step reaction and three-step reactions from cheap raw materials, respectively. Based on CNPz and DCNPz, two acceptor-acceptor (A-A) polymers, P(DPP-CNPz) and P(DPP-DCNPz) are successfully developed, featuring deep-positioned lowest unoccupied molecular orbital (LUMO) energy levels, which are beneficial to n-type organic thin-film transistors (OTFTs) and OTEs performance. An optimal unipolar electron mobility of 0.85 and 1.85 cm2 V-1 s-1 is obtained for P(DPP-CNPz) and P(DPP-DCNPz), respectively. When doped with N-DMBI, P(DPP-CNPz) and P(DPP-DCNPz) show high n-type electrical conductivities/power factors of 25.3 S cm-1 /41.4 µW m-1 K-2 , and 33.9 S cm-1 /30.4 µW m-1 K-2 , respectively. Hence, the cyano-functionalized pyrazine CNPz and DCNPz represent a new class of structurally simple, low-cost and readily accessible electron-deficient building block for constructing n-type polymer semiconductors.

circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling.

OBJECTIVES: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. MATERIALS AND METHODS: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. RESULTS: Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. CONCLUSION: The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients.

Sex discrepancy in establishing mouse visceral obesity model induced by high-fat diet. / é«˜è„‚é¥®é£Ÿè¯±å¯¼çš„å† è„è‚¥èƒ–å°é¼ æ¨¡åž‹å­˜åœ¨æ€§åˆ«å·®å¼‚.

OBJECTIVES: To establish a mouse visceral obesity model, and to investigate the effect of animal sex on this model. METHODS: Thirty-two 4-week-old BALB/c mice were randomly divided into female control group, female high-fat group, male control group and male high-fat group with 8 mice in each group.The control groups were given ordinary diet, and the high-fat groups were given high-fat diet. After 12 weeks of feeding, body weight, visceral fat, fasting blood glucose, glucose tolerance, blood lipid and metabolism-related hormone levels were measured, and the composition of gut microbiota of mice was analyzed by 16S rRNA sequencing. RESULTS: The high fat diet resulted in a significant increase of body weight and visceral fat content in male mice; the pathological results showed significantly increased fat area, accumulation of liver fat droplets, increased total cholesterol, fasting blood glucose, oral glucose tolerance and serum insulin levels (all P<0.05), as well as significant insulin resistance (P<0.01). However, the above changes were not significant in female mice. Compared with the control groups, there was an increase in the relative abundance of obesity-related gut microbiota in the model groups (such as Blautia), and the microbiota structure changed significantly, while the changes were less obvious in female mice. CONCLUSIONS: A visceral obesity mouse model has been stably established by feeding high-fat diet in BALB/c male mice, showing visceral fat accumulation, metabolic dysfunction and gut microbiota changes; while female mice are not sensitive in this obesity model.

Antibiotic cocktail-induced gut microbiota depletion in different stages could cause host cognitive impairment and emotional disorders in adulthood in different manners.

Gut microbiota depletion may result in cognitive impairment and emotional disorder. This study aimed to determine the possible association between host gut microbiota, cognitive function, and emotion in various life stages and its related underlying mechanisms. Seventy-five neonatal mice were randomly divided into five groups (n = 15 per group). Mice in the vehicle group were administered distilled water from birth to death, and those in the last four groups were administered antibiotic cocktail from birth to death, from birth to postnatal day (PND) 21 (infancy), from PND 21 to 56 (adolescence), and from PND 57 to 84 (adulthood), respectively. Antibiotic exposure consistently altered the gut microbiota composition and decreased the diversity of gut microbiota. Proteobacteria were the predominant bacteria instead of Firmicutes and Bacteroidetes after antibiotic exposure in different life stages. Long-term and infant gut microbiota depletion resulted in anxiety- and depression-like behaviors, memory impairments, and increased expression of γ-aminobutyric acid type A receptor α1 of adult mice. Long-term antibiotic exposure also significantly decreased serum interleukin (IL)-1ß, IL-10, and corticosterone of adult mice. Gut microbiota depletion in adolescence resulted in anxiety-like behaviors, short-term memory decline, decreased serum interferon-γ (IFN-γ), mRNA expression of 5-hydroxytryptamine receptor 1A, and neuropeptide Y receptor Y2 in the prefrontal cortex of adult mice. Antibiotic exposure in adulthood damaged short-term memory and decreased serum IL-10, IFN-γ, and increased γ-aminobutyric acid type B receptor 1 mRNA expression of adult mice. These results suggest that antibiotic-induced gut microbiota depletion in the long term and infancy resulted in the most severe cognitive and emotional disorders followed by depletion in adolescence and adulthood. These results also suggest that gut microbes could influence host cognitive function and emotion in a life stage-dependent manner by affecting the function of the immune system, hypothalamic-pituitary-adrenal axis, and the expression of neurochemicals in the brain.

Cerebellar Oscillations in Familial and Sporadic Essential Tremor.

Enhanced cerebellar oscillations have recently been identified in essential tremor (ET) patients as a key pathophysiological change. Since ET is considered a heterogeneous group of diseases, we investigated whether cerebellar oscillations differ in ET subtypes (familial vs. sporadic). This study aims to determine cerebellar physiology in familial and sporadic ET. Using surface electroencephalogram, we studied cerebellar physiology in 40 ET cases (n = 22 familial and n = 18 sporadic) and 20 age-matched controls. Both familial and sporadic ET cases had an increase in the intensity of cerebellar oscillations when compared to controls. Interestingly, cerebellar oscillations correlated with tremor severity in familial ET but not in sporadic ET. Our study demonstrated that ET cases have enhanced cerebellar oscillations, and the different relationships between cerebellar oscillations and tremor severity in familial and sporadic ET suggest diverse cerebellar pathophysiology.

Pyrolysis kinetics and environmental risks of oil-based drill cuttings at China's largest shale gas exploitation site.

Chongqing Fuling shale gas field, the largest shale gas exploration site in China, produces a large amount of oil-based drill cuttings (OBDC) every year, which is a hazardous waste. Traditional treatment methods such as solidification/stabilization did not recycle the valuable components such as petroleum hydrocarbons. Pyrolysis is proven to be an efficient method that can recover those components. This study firstly investigated the pyrolysis kinetics by two different methods on the basis of detailed material characterization, and then taking the workers and the surrounding ecological environment as the analysis object, the human health risk assessment (HHRA) and ecological risk assessment were evaluated respectively before and after pyrolysis. The results showed that the pyrolysis of OBDC was divided into three stages, and the cracking of light hydrocarbons stage was the key control step for pyrolysis process. The activation energy E increased gradually during the pyrolysis progress. The HHRA results showed that pyrolysis could greatly reduce the non-carcinogenic risk, carcinogenic risk and ecological risk by 59.6 %, 62.8 % and 75 % respectively. However, the carcinogenic risk after pyrolysis was still higher than the critical value 10-6.

[Bifidobacterium bifidum TMC3115 Promotes Early Life Intestinal Microbiota Building to Alleviate Symptoms of Inflammatory Bowel Disease].

Objective: To investigate the effects of using Bifidobacterium bifidum TMC3115 in early life on intestinal microbiota and immune functions and the long-term impact on inflammatory bowel disease. Methods: Fourteen pregnant BALB/c mice were purchased and 84 newborn BALB/c mice were subsequently obtained. Then, the newborn mice were randomly assigned to a normal saline (NS) group and a TMC3115 group, given via oral gavage normal saline and TMC3115, respectively, at a daily volume of 0.2 mL for each mouse. About 42 mice were assigned to each group. The gavage was stopped after 3 weeks. At this point, half of the mice in each group were sacrificed, and then the remaining mice in each group were randomly divided into NS-water group, NS-DSS group, TMC3115-water group, and TMC3115-DSS group, with about 10 mice in each group. The mice were given regular feed until the end of week 6 when they were given 3% dextran sulphate sodium (DSS) ad libitum for 4 days to establish the enteritis model, while the non-modeling groups were given pure water ad libitum. The experiment ended after 6 weeks and 4 days. The weekly body mass changes of the mice were documented. The intestinal tissue at the end of the experiment and the fecal samples, spleen and serum of the mice at 3 weeks and at the end of the experiment were collected to determine the pathology scores of colonic inflammation, the composition of fecal gut microbiota, spleen organ index and the mass concentration of serum cytokines. Results: 1) At the end of the experiment, the inflammatory pathology score was significantly lower in the TMC3115-DSS group compared with that of the Saline-DSS group ( P<0.05), with less disruption of colonic crypt structures and other structures, less inflammatory infiltration, and more intact epithelial structures. 2) At 3 weeks, in comparison with those of the NS group, the relative abundance of Bifidobacteriumwas significantly higher in the feces of the TMC3115 ( P<0.05), the relative abundance of both Enterococcusand Staphylococcuswas lower ( P<0.05), the splenic organ index was significantly higher ( P<0.05), and interleukin (IL)-10 was significantly decreased ( P<0.05), while there was no significant change in IL-6 or TNF-α ( P>0.05). At the end of the experiment, in comparison with those of the NS-DSS group that undergone DSS induction, the TMC3115-DSS group had reduced relative abundance of Staphylococcus, Staphylococcus tumefaciens and Escherichia/ Shigellain the feces ( P<0.05), while the splenic organ index was significantly higher ( P<0.05), and there were no significant changes in IL-6 or TNF-α ( P>0.05). Conclusion: The use of TMC3115 in early life promotes the construction of gut microbiota in neonatal mice, thereby producing a long-term effect that alleviates colitis in mice, but the mechanisms involved are still not fully understood.

Imide-Functionalized Fluorenone and Its Cyanated Derivative Based n-Type Polymers: Synthesis, Structure-Property Correlations, and Thin-Film Transistor Performance.

The development of high-performance n-type polymer semiconductors is powered by the design and synthesis of electron-deficient building blocks with optimized physicochemical properties. By meticulously installing an imide group onto fluorene and its cyanated derivative, we report here two very electron-deficient building blocks, imide-functionalized fluorenone (FOI) and its cyanated derivative (FCNI), both featuring a deep-lying lowest unoccupied molecular orbital energy level down to -4.05 eV and highly coplanar framework, endowing them ideal units for constructing n-type polymers. Thus, a series of polymers are built from them, exhibiting unipolar n-type transport character with a highest electron mobility of 0.11 cm2  V-1 s-1 . Hence, FOI and FCNI offer a remarkable platform for accessing high-performance n-type polymers and the imide functionalization of appropriate (hetero)arenes is a powerful strategy for developing polymers with deep-lying LUMOs for n-type organic electronics.

Thiazole Imide-Based All-Acceptor Homopolymer with Branched Ethylene Glycol Side Chains for Organic Thermoelectrics.

n-Type semiconducting polymers with high thermoelectric performance remain challenging due to the scarcity of molecular design strategy, limiting their applications in organic thermoelectric (OTE) devices. Herein, we provide a new approach to enhance the OTE performance of n-doped polymers by introducing acceptor-acceptor (A-A) type backbone bearing branched ethylene glycol (EG) side chains. When doped with 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI), the A-A homopolymer PDTzTI-TEG exhibits n-type electrical conductivity (σ) up to 34 S cm-1 and power factor value of 15.7 µW m-1 K-2 . The OTE performance of PDTzTI-TEG is far greater than that of homopolymer PBTI-TEG (σ=0.27 S cm-1 ), indicating that introducing electron-deficient thiazole units in the backbone further improves the n-doping efficiency. These results demonstrate that developing A-A type polymers with EG side chains is an effective strategy to enhance n-type OTE performance.

Cardiac Ischemic Preconditioning Promotes MG53 Secretion Through H2O2-Activated Protein Kinase C-δ Signaling.

BACKGROUND: Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia/reperfusion injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (mitsugumin 53; also called TRIM72), not only plays an essential role in IPC-mediated cardioprotection against ischemia/reperfusion injury but also ameliorates mechanical damage. In addition to its intracellular actions, as a myokine/cardiokine, MG53 can be secreted from the heart and skeletal muscle in response to metabolic stress. However, it is unknown whether IPC-mediated cardioprotection is causally related to MG53 secretion and, if so, what the underlying mechanism is. METHODS: Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo, isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. Moreover, using recombinant MG53 proteins, we investigated the potential biological function of secreted MG53 in the context of IPC and ischemia/reperfusion injury. RESULTS: We found that IPC triggered robust MG53 secretion in rodents in vivo, perfused hearts, and cultured cardiac myocytes without causing cell membrane leakage. Mechanistically, IPC promoted MG53 secretion through H2O2-evoked activation of protein kinase-C-δ. Specifically, IPC-induced myocardial MG53 secretion was mediated by H2O2-triggered phosphorylation of protein kinase-C-δ at Y311, which is necessary and sufficient to facilitate MG53 secretion. Functionally, systemic delivery of recombinant MG53 proteins to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice but also protected rodent hearts from ischemia/reperfusion injury even in the absence of IPC. Moreover, oxidative stress by H2O2 augmented MG53 secretion, and MG53 knockdown exacerbated H2O2-induced cell injury in human embryonic stem cell-derived cardiomyocytes, despite relatively low basal expression of MG53 in human heart. CONCLUSIONS: We conclude that IPC and oxidative stress can trigger MG53 secretion from the heart via an H2O2-protein kinase-C-δ-dependent mechanism and that extracellular MG53 can participate in IPC protection against cardiac ischemia/reperfusion injury.

Volume-associated hemodynamic variables for prediction of cardiac surgery-associated acute kidney injury.

BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.

Application of group LASSO regression based Bayesian networks in risk factors exploration and disease prediction for acute kidney injury in hospitalized patients with hematologic malignancies.

BACKGROUND: Patients who were diagnosed with hematologic malignancies (HM) had a higher risk of acute kidney injury (AKI). This study applies the Bayesian networks (BNs) to investigate the interrelationships between AKI and its risk factors among HM patients, and to evaluate the predictive and inferential ability of BNs model in different clinical settings. METHODS: During 2014 and 2015, a total of 2501 inpatients with HM were recruited in this retrospective study conducted in a tertiary hospital, Shanghai of China. Patients' demographics, medical history, clinical and laboratory records on admission were extracted from the electronic medical records. Candidate predictors of AKI were screened in the group-LASSO (gLASSO) regression, and then they were incorporated into BNs analysis for further interrelationship modeling and disease prediction. RESULTS: Of 2395 eligible patients with HM, 370 episodes were diagnosed with AKI (15.4%). Patients with multiple myeloma (24.1%) and leukemia (23.9%) had higher incidences of AKI, followed by lymphoma (13.4%). Screened by the gLASSO regression, variables as age, gender, diabetes, HM category, anti-tumor treatment, hemoglobin, serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum uric acid, serum sodium and potassium level were found with significant associations with the occurrence of AKI. Through BNs analysis, age, hemoglobin, eGFR, serum sodium and potassium had directed connections with AKI. HM category and anti-tumor treatment were indirectly linked to AKI via hemoglobin and eGFR, and diabetes was connected with AKI by affecting eGFR level. BNs inferences concluded that when poor eGFR, anemia and hyponatremia occurred simultaneously, the patients' probability of AKI was up to 78.5%. The area under the receiver operating characteristic curve (AUC) of BNs model was 0.835, higher than that in the logistic score model (0.763). It also showed a robust performance in 10-fold cross-validation (AUC: 0.812). CONCLUSION: Bayesian networks can provide a novel perspective to reveal the intrinsic connections between AKI and its risk factors in HM patients. The BNs predictive model could help us to calculate the probability of AKI at the individual level, and follow the tide of e-alert and big-data realize the early detection of AKI.

Efficacy of Early Goal-Directed Renal Replacement Therapy for the Treatment of Acute Kidney Injury After Heart Transplantation: A Single-Center 10-Year Experience.

OBJECTIVE: Acute kidney injury (AKI) after heart transplantation is a common and serious complication. The present study aimed to evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of AKI after heart transplantation. DESIGN: Retrospective, observational study. SETTING: Grade A tertiary hospital that performs more than 4,000 cardiac surgery procedures per year. PARTICIPANTS: Patients who underwent heart transplantation with postoperative AKI and received renal replacement therapy from January 2008 to June 2018. INTERVENTIONS: Patients were divided into a late GDRRT group (LGDRRT) (January 2008-September 2012) or an early GDRRT group (EGDRRT) (October 2012-June 2018). RESULTS: The LGDRRT group comprised 30 patients, and the EGDRRT group comprised 46 patients. Duration between surgery to renal replacement therapy (RRT) initiation in the EGDRRT group was significantly shorter than in the LGDRRT group (1 [1-3] d v 2 [2-3] d; p = 0.020). The in-hospital mortality in the EGDRRT group was significantly lower than that of the LGDRRT group (39.1% v 63.3%; p = 0.039). After multivariate adjustment for confounding factors, the hazard ratio for death in the LGDRRT group relative to the EGDRRT group was 2.028 (95% confidence interval 1.072-3.655; p = 0.048). Length of intensive care unit and hospital stays in the EGDRRT group was significantly shorter than that of the LGDRRT group (26 ± 18 d v 38 ± 20 d; p = 0.008 and 38 ± 33 d v 64 ± 45 d; p = 0.005, respectively). The complete renal recovery rate was much greater in the EGDRRT group than that of the LGDRRT group (50.0% v 20.0%; p < 0.001). Serum creatinine at discharge was significantly less in the EGDRRT group than that of the LGDRRT group (134.8 ± 97.3 µmol/L v 220.7 ± 113.6 µmol/L; p < 0.001). Cost of RRT in the EGDRRT group was significantly less than that of the LGDRRT group (0.54 ± 0.10 v. 0.63 ± 0.11 ten thousand USD; p < 0.001). CONCLUSIONS: For heart transplantation recipients with AKI, EGDRRT can reduce the in-hospital mortality and the length of intensive care unit and hospital stays, improve the complete renal recovery rate, and reduce the cost of RRT.

Estimating 24-Hour Urinary Sodium Excretion From Spot Urine Samples in Chronic Kidney Disease Patients.

OBJECTIVE: Spot urine sodium and associated estimating equations provide a suitable alternative assessment of 24-hour sodium excretion in many large-scale studies, but not in chronic kidney disease (CKD) patients with decreased renal function. Herein, we aimed to develop a novel predictive equation. DESIGN AND METHODS: We retrospectively enrolled all CKD patients at Stage 1-4 who received spot and 24-hour urinary analysis in our single center from January 1, 2014 to December 31, 2017. Multiple linear regression analysis generated a predictive equation for estimating 24-hour sodium excretion from spot urine samples in the derivation cohort admitted from 2014 to 2015, and then we assessed this predictive equation in a validation cohort admitted from 2016 to 2017. RESULTS: All 5,235 patients were finally analyzed and divided into derivation (n = 2,460) and validation (n = 2,775) cohort according to the admission date. We generated a predictive equation and defined it as "CKDSALT" equation because it was used for the estimation of salt intake in CKD patients. When we measured sodium excretion as the gold standard, we compared this novel validation with other 3 equations: Kawasaki, INTERSALT, and Tanaka. The Bland-Altman plots indicated that the CKDSALT equation showed the lowest bias with limits of agreement (bias = -1.25 mmol, 95% confidence interval -121.3 to 123.8), and the best performance in any subgroup analysis: male and female, old and young, different levels of body mass index, various levels of estimated glomerular filtration rate, and 24-hour urine volume. The CKDSALT equation also had the highest Pearson (0.745) and intraclass correlation coefficient (0.853, 95% confidence interval 0.841-0.863) in all validation cohort and the above subgroups. CONCLUSION: Spot urine method by CKDSALT equation may be promising for estimating 24-hour urinary sodium excretion in CKD patients with normal renal function and patients with decreased estimated glomerular filtration rate.

Prediction models for acute kidney injury in patients with gastrointestinal cancers: a real-world study based on Bayesian networks.

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.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

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.

Evaluation of five different renal recovery definitions for estimation of long-term outcomes of cardiac surgery associated acute kidney injury.

BACKGROUND: The commonly used recommended criteria for renal recovery are not unequivocal. This study compared five different definitions of renal recovery in order to evaluate long-term outcomes of cardiac surgery associated acute kidney injury (CSA-AKI). METHODS: Patients who underwent cardiac surgery between April 2009 and April 2013 were enrolled and divided into acute kidney injury (AKI) and non-AKI groups. The primary endpoint was 3-year major adverse events (MAEs) including death, new dialysis and progressive chronic kidney disease (CKD). We compared five criteria for complete renal recovery: Acute Renal Failure Trial Network (ATN): serum creatinine (SCr) at discharge returned to within baseline SCr + 0.5 mg/dL; Acute Dialysis Quality Initiative (ADQI): returned to within 50% above baseline SCr; Pannu: returned to within 25% above baseline SCr; Kidney Disease: Improving Global Outcomes (KDIGO): eGFR at discharge ≥60 mL/min/1.73 m2; Bucaloiu: returned to ≥90% baseline estimated glomerular filtration rate (eGFR). Multivariate regression analysis was used to compare risk factors for 3-year MAEs. RESULTS: The rate of complete recovery for ATN, ADQI, Pannu, KDIGO and Bucaloiu were 84.60% (n = 1242), 82.49% (n = 1211), 60.49% (n = 888), 68.60% (n = 1007) and 46.32% (n = 680). After adjusting for confounding factors, AKI with complete renal recovery was a risk factor for 3-year MAEs (OR: 1.69, 95% CI: 1.20-2.38, P <  0.05; OR: 1.45, 95% CI: 1.03-2.04, P <  0.05) according to ATN and ADQI criteria, but not for KDIGO, Pannu and Bucaloiu criteria. We found that relative to patients who recovered to within 0% baseline SCr or recovered to ≥100% baseline eGFR, the threshold values at which significant differences in 3-year MAEs were observed were > 30% or > 0.4 mg/dL above baseline SCr or < 70% of baseline eGFR. CONCLUSIONS: ADQI or ATN-equivalent criteria may overestimate the extent of renal recovery, while KDIGO, Pannu and Bucaloiu equivalent criteria may be more appropriate for clinical use. Our analyses revealed that SCr at discharge > 30% or > 0.4 mg/dL of baseline, or eGFR < 70% of baseline led to significant 3-year MAE incidence differences, which may serve as hints for new definitions of renal recovery.

Simultaneous determination of major components of Huangqi-Honghua extract in rat plasma using LC-MS/MS and application to a pharmacokinetic study.

A sensitive and reliable LC-MS/MS method was developed and validated for simultaneous quantification of the major components of Huangqi-Honghua extact in rat plasma, including hydroxysafflor yellow A (HSYA), astragaloside IV (ASIV), calycosin-7-O-ß-d-glucoside (CAG), calycosin, calycosin-3'-O-glucuronide (C-3'-G) and calycosin-3'-O-sulfate (C-3'-S). After extraction by protein precipitation with acetonitrile and methanol from plasma, the analytes were separated on a Hypersil BDS C18 column by gradient elution with acetonitrile and 5 mM ammonium acetate. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source switched between negative and positive modes. HSYA was monitored in negative ionization mode from 0 to 4.9 min, and ASIV, CAG, calycosin, C-3'-G and C-3'-S were determined in positive ionization mode from 4.9 to 10 min. The lower limits of quantification of the analytes were 6.25 ng/mL for HSYA, 0.781 ng/mL for CAG and 1.56 ng/mL for ASIV and calycosin. The intra- and inter-assay precision (RSD) values were within 13.43%, and accuracy (RE) ranged from -8.75 to 9.92%. The validated method was then applied to the pharmacokinetic study of HSYA, ASIV, CAG, calycosin, C-3'-G and C-3'-S in rat after an oral administration of Huangqi-Honghua extract.