Publications by authors named "Chunbo Chen"

53 Publications

Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study.

Drug Des Devel Ther 2021 19;15:2129-2141. Epub 2021 May 19.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, 510080, Guangdong, People's Republic of China.

Purpose: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients.

Methods: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L.

Results: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function.

Conclusion: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.
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http://dx.doi.org/10.2147/DDDT.S303497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142937PMC
May 2021

A nomogram incorporating functional and tubular damage biomarkers to predict the risk of acute kidney injury for septic patients.

BMC Nephrol 2021 May 13;22(1):176. Epub 2021 May 13.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, 510080, Guangzhou, PR China.

Background: Combining tubular damage and functional biomarkers may improve prediction precision of acute kidney injury (AKI). Serum cystatin C (sCysC) represents functional damage of kidney, while urinary N-acetyl-β-D-glucosaminidase (uNAG) is considered as a tubular damage biomarker. So far, there is no nomogram containing this combination to predict AKI in septic cohort. We aimed to compare the performance of AKI prediction models with or without incorporating these two biomarkers and develop an effective nomogram for septic patients in intensive care unit (ICU).

Methods: This was a prospective study conducted in the mixed medical-surgical ICU of a tertiary care hospital. Adults with sepsis were enrolled. The patients were divided into development and validation cohorts in chronological order of ICU admission. A logistic regression model for AKI prediction was first constructed in the development cohort. The contribution of the biomarkers (sCysC, uNAG) to this model for AKI prediction was assessed with the area under the receiver operator characteristic curve (AUC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). Then nomogram was established based on the model with the best performance. This nomogram was validated in the validation cohort in terms of discrimination and calibration. The decision curve analysis (DCA) was performed to evaluate the nomogram's clinical utility.

Results: Of 358 enrolled patients, 232 were in the development cohort (69 AKI), while 126 in the validation cohort (52 AKI). The first clinical model included the APACHE II score, serum creatinine, and vasopressor used at ICU admission. Adding sCysC and uNAG to this model improved the AUC to 0.831. Furthermore, incorporating them significantly improved risk reclassification over the predictive model alone, with cNRI (0.575) and IDI (0.085). A nomogram was then established based on the new model including sCysC and uNAG. Application of this nomogram in the validation cohort yielded fair discrimination with an AUC of 0.784 and good calibration. The DCA revealed good clinical utility of this nomogram.

Conclusions: A nomogram that incorporates functional marker (sCysC) and tubular damage marker (uNAG), together with routine clinical factors may be a useful prognostic tool for individualized prediction of AKI in septic patients.
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http://dx.doi.org/10.1186/s12882-021-02388-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120900PMC
May 2021

Nomogram to predict survival outcome of patients with veno-arterial extracorporeal membrane oxygenation after refractory cardiogenic shock.

Postgrad Med 2021 May 20:1-10. Epub 2021 May 20.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, The Second School of Clinical Medicine, Southern Medical University, Gaozhou, Guangdong, China.

: This study aims to develop a nomogram model to predict the survival of refractory cardiogenic shock (RCS) patients that received veno-arterial extracorporeal membrane oxygenation (VA-ECMO).: A total of 235 and 209 RCS patients were supported with VA-ECMO from January 2018 to December 2019 in Guangdong Provincial People's Hospital, and from January 2020 to December 2020 in four third-grade and class-A hospitals were a development cohort (DC) and validation cohort (VC), respectively. Finally, 137 and 98 patients were included in the DC and VC. Multivariate logistic regression analysis was used to identify variables, and only these independent risk factors were used to establish the nomogram model. The receiver operating characteristic curve (ROC), calibration plot, decision curve, and clinical impact curves were used to evaluate the nomogram's discriminative ability, predictive accuracy, and clinical application value.: Pre-ECMO cardiogenic arrest (pre-ECA), lactate (Lac), inotropic score (IS), and modified nutrition risk in the critically ill score (mNUTRIC score) were incorporated into the nomogram. This showed good discrimination in the DC, with an area under ROC (AUROC) and a 95% confidence interval (CI) of 0.959 (0.911-0.986). The AUROC (95% CI) of the VC was 0.928 (0.858-0.971). The calibration plots of the DC and VC presented good calibration results. The decision curve and clinical impact curve of the nomogram provided improved benefits for RCS patients.: This study established a prediction nomogram composed of pre-ECA, Lac, IS, and mNUTRIC scores that could help clinicians to predict the survival probability at hospital discharge precisely and rapidly for RCS patients that received VA-ECMO.
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http://dx.doi.org/10.1080/00325481.2021.1925562DOI Listing
May 2021

Dysbiosis of intestinal microbiota in critically ill patients and risk of in-hospital mortality.

Am J Transl Res 2021 15;13(3):1548-1557. Epub 2021 Mar 15.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China.

Background: Despite the essential functions of the intestinal microbiota in human physiology, little research was reported on gut microbiota alterations in intensive care patients. This investigation examined the dysbacteriosis of intestinal flora in critically ill patients and evaluated the prognostic performance of this dysbiosis to predict in-hospital mortality.

Methods: A prospective cohort of patients were consecutively recruited in the Intensive Care Units (ICUs) in Guangdong Provincial People's Hospital from March 2017 through October 2017. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were assessed, and fecal samples were taken for examination within 24 hours of ICU admission. The taxonomic composition of the intestinal microbiome was determined using 16S rDNA gene sequencing. Patients were divided into survival and death groups based on hospital outcomes. The two groups were statistically compared using the Wilcoxon test and Metastats analysis. The genera of bacteria showing significantly different abundance between groups were assessed as predictors of in-hospital death. The prognostic value of bacterial abundance alone and in combination with APACHE II or SOFA score was evaluated using the area under the receiver operating characteristic curve (AUROC).

Results: Among the 61 patients examined, 12 patients (19.7%) died during their hospital stay. abundance was higher in the survival group than the death group ( = 0.031). The AUROC of abundance in identifying in-hospital death at a cut-off probability of 0.0041 was 0.718 (95% confidence interval [CI], 0.588-0.826). The panel of abundance plus SOFA (AUROC, 0.882; 95% CI, 0.774-0.950) outperformed SOFA (AUROC, 0.649; 95% CI, 0.516-0.767; = 0.012) and abundance alone ( = 0.007). The panel of abundance plus APACHE II (AUROC, 0.876; 95% CI, 0.766-0.946) outperformed APACHE II (AUROC, 0.724; 95% CI, 0.595-0.831; = 0.035) and abundance alone ( = 0.012).

Conclusions: Dysbiosis of intestinal microbiota with variable degrees of reduction in abundance exhibited promising performance in the predicting of in-hospital mortality and provides incremental prognostic value to existing scoring systems in the adult intensive care unit (ICU) setting.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014420PMC
March 2021

Lipidomic alteration of plasma in cured COVID-19 patients using ultra high-performance liquid chromatography with high-resolution mass spectrometry.

Biosci Rep 2021 03;41(3)

Center of Scientific Research, Maoming People's Hospital, Maoming 525000, China.

Background: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood.

Methods: In the present study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison.

Results: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters (ChE). Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways.

Conclusions: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to undergo consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.
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http://dx.doi.org/10.1042/BSR20204305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937909PMC
March 2021

Establishment and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Tigecycline in Critically Ill Patients.

Int J Anal Chem 2020 29;2020:6671392. Epub 2020 Dec 29.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, Guangdong, China.

Utilizing tigecycline-d9 as an internal standard (IS), we establish and validate a simple, effective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative measurement of tigecycline (TGC) in patient plasma. Acetonitrile was used as a precipitant to process plasma samples by a protein precipitation method. The analyte and IS were separated on an HSS T3 (2.1 × 100 mm, 3.5 m) chromatographic column using isocratic program with a mobile phase comprising of 80% solvent A (water containing 0.1% formic acid (v/v) with 5 mM ammonium acetate) and 20% solvent B (acetonitrile) with a flow rate of 0.3 mL/min. The mass spectrometer, scanning in multireaction monitoring (MRM) mode and using an electrospray ion source (ESI), operated in the positive-ion mode. The ion pairs used for quantitative analysis were / 586.4 ⟶ 513.3 and / 595.5 ⟶ 514.3 for TGC and the IS, respectively. The range of the linear calibration curve obtained with this approach was 50-5000 ng/ml. Intra- and interbatch precision for TGC quantitation were less than 7.2%, and the accuracy ranged from 93.4 to 101.8%. The IS-normalized matrix effect was 87 to 104%. Due to its high precision and accuracy, this novel method allows for fast quantitation of TGC with a total analysis time of 2 min. This approach was effectively applied to study the pharmacokinetics of TGC in critically ill adult patients.
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http://dx.doi.org/10.1155/2020/6671392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785388PMC
December 2020

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

Ann Transl Med 2020 Nov;8(21):1438

Institute of Nephrology, Zhong Da Hospital, Nanjing, China.

Background: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children.

Methods: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Results: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI.

Conclusions: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.
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http://dx.doi.org/10.21037/atm-20-2284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723554PMC
November 2020

Human appropriation of net primary production estimates in the Xinjiang grasslands.

PLoS One 2020 2;15(12):e0242478. Epub 2020 Dec 2.

Key Laboratory of Restoration Ecology for Cold Regions Laboratory in Qinghai, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai, China.

The human appropriation of net primary production (HANPP) was developed to estimate the intensity of human activities in natural ecosystems, which is still unclear in the Xinjiang grasslands. Using the Biome-Biogeochemical Cycle (Biome-BGC) grazing model in combination with field data, we assessed the HANPP and explored its spatiotemporal patterns in the Xinjiang grasslands. Our results showed that (1) the HANPP increased from 38 g C/m2/yr in 1979 to 88 g C/m2/yr in 2012, with an average annual increase of 1.47%. The HANPP was 80 g C/m2/yr, which represented 51% of the potential net primary production (NPPpot), and the HANPP efficiency was 70% in this region. (2) The areas with high HANPP values mainly occurred in northern Xinjiang and northwest of the Tianshan Mountains, while areas with low HANPP values mainly occurred in southern Xinjiang and southwest of the Tianshan Mountains. (3) Interannual variations in HANPP and NPPpot were significantly positively correlated (P<0.01). Interannual variations in HANPP efficiency and grazing intensity were negatively correlated (P<0.01). These results can help identify the complex impacts of human activities on grassland ecosystems and provide basic data for grassland management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710112PMC
January 2021

The effect of glucocorticoids on serum cystatin C in identifying acute kidney injury: a propensity-matched cohort study.

BMC Nephrol 2020 11 27;21(1):519. Epub 2020 Nov 27.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.

Background: Glucocorticoids may impact the accuracy of serum cystatin C (sCysC) in reflecting renal function. We aimed to assess the effect of glucocorticoids on the performance of sCysC in detecting acute kidney injury (AKI) in critically ill patients.

Methods: A prospective observational cohort study was performed in a general intensive care unit (ICU). Using propensity score matching, we successfully matched 240 glucocorticoid users with 960 non-users among 2716 patients. Serum creatinine (SCr) and sCysC were measured for all patients at ICU admission. Patients were divided into four groups based on cumulative doses of glucocorticoids within 5 days before ICU admission (Group I: non-users; Group II: 0 mg < prednisone ≤50 mg; Group III: 50 mg < prednisone ≤150 mg; Group IV: prednisone > 150 mg). We compared the performance of sCysC for diagnosing and predicting AKI in different groups using the area under the receiver operator characteristic curve (AUC).

Results: A total of 240 patients received glucocorticoid medication within 5 days before ICU admission. Before and after matching, the differences of sCysC levels between glucocorticoid users and non-users were both significant (P <  0.001). The multiple linear regression analysis revealed that glucocorticoids were independently associated with sCysC (P <  0.001). After matching, the group I had significantly lower sCysC levels than the group III and group IV (P <  0.05), but there were no significant differences in sCysC levels within different glucocorticoids recipient groups (P > 0.05). Simultaneously, we did not find significant differences in the AUC between any two groups in the matched cohort (P > 0.05).

Conclusions: Glucocorticoids did not impact the performance of sCysC in identifying AKI in critically ill patients.
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http://dx.doi.org/10.1186/s12882-020-02165-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694927PMC
November 2020

C-reactive protein concentration as a risk predictor of mortality in intensive care unit: a multicenter, prospective, observational study.

BMC Anesthesiol 2020 11 23;20(1):292. Epub 2020 Nov 23.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.

Background: It is not clear whether there are valuable inflammatory markers for prognosis judgment in the intensive care unit (ICU). We therefore conducted a multicenter, prospective, observational study to evaluate the prognostic role of inflammatory markers.

Methods: The clinical and laboratory data of patients at admission, including C-reactive protein (CRP), were collected in four general ICUs from September 1, 2018, to August 1, 2019. Multivariate logistic regression was used to identify factors independently associated with nonsurvival. The area under the receiver operating characteristic curve (AUC-ROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the effect size of different factors in predicting mortality during ICU stay. 3 -knots were used to assess whether alternative cut points for these biomarkers were more appropriate.

Results: A total of 813 patients were recruited, among whom 121 patients (14.88%) died during the ICU stay. The AUC-ROC values of PCT and CRP for discriminating ICU mortality were 0.696 (95% confidence interval [CI], 0.650-0.743) and 0.684 (95% CI, 0.633-0.735), respectively. In the multivariable analysis, only APACHE II score (odds ratio, 1.166; 95% CI, 1.129-1.203; P = 0.000) and CRP concentration > 62.8 mg/L (odds ratio, 2.145; 95% CI, 1.343-3.427; P = 0.001), were significantly associated with an increased risk of ICU mortality. Moreover, the combination of APACHE II score and CRP > 62.8 mg/L significantly improved risk reclassification over the APACHE II score alone, with NRI (0.556) and IDI (0.013). Restricted cubic spline analysis confirmed that CRP concentration > 62.8 mg/L was the optimal cut-off value for differentiating between surviving and nonsurviving patients.

Conclusion: CRP markedly improved risk reclassification for prognosis prediction.
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http://dx.doi.org/10.1186/s12871-020-01207-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680994PMC
November 2020

Anti-Inflammatory and Intestinal Microbiota Modulation Properties of Jinxiang Garlic ( L.) Polysaccharides toward Dextran Sodium Sulfate-Induced Colitis.

J Agric Food Chem 2020 Nov 23;68(44):12295-12309. Epub 2020 Oct 23.

School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China.

Garlic polysaccharides are great potential agents because of their anti-inflammation, antioxidation, and immunomodulation properties. However, few studies have reported their anti-inflammatory effects on improving the colon system and corresponding intestinal microbiota. Herein, a water-soluble garlic polysaccharide (WSGP) was extracted from Jinxiang garlic to evaluate its effects on ameliorating dextran sulfate sodium (DSS)-induced colitis in a mouse model. The results showed that (1) after administration of the WSGP (200 or 400 mg/kg/day), the feed intake, body weight, and colon length of colitic mice were increased, while the disease activity index and the histological score of colitic mice were decreased; (2) the WSGP reduced the colonic tissue damage and inhibited the expression of inflammatory factors (interleukin 6, interleukin 1 beta , and tumor necrosis factor alpha); and (3) the WSGP enhanced the production of short-chain fatty acids and improved the composition of intestinal microbiota. The key microorganisms, including Muribaculaceae, Lachnospiraceae, , , , , and , were identified to be associated with inflammatory bowel diseases. Taken together, this study proved that WSGP supplementation could alleviate DSS-induced colitis by improving mucosal barriers, blocking proinflammatory cytokines, and modulating gut microbiota.
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http://dx.doi.org/10.1021/acs.jafc.0c04773DOI Listing
November 2020

Response to the letter: Comment on "simo decoction versus domperidone suspension for post-pyloric spiral nasoenteric tube placement: A multicenter, randomized, non-inferiority trial".

Clin Nutr 2020 12 9;39(12):3847-3848. Epub 2020 Oct 9.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080, Guangdong, China. Electronic address:

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http://dx.doi.org/10.1016/j.clnu.2020.09.055DOI Listing
December 2020

Metal-ion-assisted structural and anomeric analysis of Amadori compounds by electrospray ionization mass spectrometry.

Rapid Commun Mass Spectrom 2021 Jan;35(1):e8960

Center of Scientific Research, Maoming People's Hospital, Maoming, 525000, China.

Rationale: The Maillard reaction plays an important role in food, physiology and traditional Chinese medicine, and its primary reaction products are formed through Amadori rearrangement by reducing sugars and amino acids. The analysis of the characteristic fragmentation and of the glycosidic bond configuration of Amadori compounds will promote their fast discovery and identification by mass spectrometry.

Methods: Four Amadori compounds that reduce disaccharides and proline/tryptophan were used to investigate the fragmentation mechanisms via tandem mass spectrometry (MS/MS) with different alkali metal ion adducts. Cu could be used to distinguish glycosidic bond configurations of the reducing disaccharides in the full-scan mass spectra. Quantum calculations were also conducted for a single Amadori compound with Cu for analysis of the most optimized configurations and binding energies of metal complexes.

Results: MS/MS analysis of Amadori-alkali metal complexes revealed that the radius of the alkali metal ions had profound effects on the degree of fragmentation of such compounds, among which lithium-cationized ions produced the most extensive fragmentation. Amadori compounds with different glycosidic bonds formed differently proportioned metal complexes with Cu , and the complexity of the copper complexes containing tryptophan moieties was higher than that of those containing proline moieties in the mass spectra. Quantum calculations showed that Amadori compounds with β-configurations can form more binding sites with Cu than those with α-configurations, thus making the metal complex with a single ligand more stable. In addition, the chelation of tryptophan with copper ions increased the coordination binding energy, which showed that α-configured Amadori compounds were readily able to form multi-ligand copper complexes.

Conclusions: Metal-ion-assisted analysis provides crucial information for structural and anomeric analysis of Amadori compounds by electrospray ionization mass spectrometry. Elucidation of binding sites and binding energies by quantum calculations has significantly improved the knowledge of metal complexes in the gas phase and provides background information for determining the glycosidic configuration of Amadori isomers.
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http://dx.doi.org/10.1002/rcm.8960DOI Listing
January 2021

Predicting the Suitable Geographical Distribution of under Different Climate Change Scenarios in the Three-River Region Using the MaxEnt Model.

Plants (Basel) 2020 Aug 11;9(8). Epub 2020 Aug 11.

Key Laboratory of Restoration Ecology for Cold Regions Laboratory in Qinghai, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China.

is a perennial grass with considerable academic value as a rare species owing to habitat destruction and a narrow distribution. However, its distribution remains unclear. In this study, we predicted the distribution of in the three-river region (the source of the Yangtze River, Yellow River, and Lancang River) under the context of climate change using the maximum entropy (MaxEnt) model. Under the current climate scenario, the suitable distribution mainly occurred in Yushu County and Nangqian County. The suitable distribution area of covered 3107 km, accounting for 0.57% of the three-river region. The mean diurnal air temperature range (Bio2), temperature seasonality (Bio4), and mean air temperature of the driest quarter (Bio9) contributed the most to the distribution model for , with a cumulative contribution of 81.4%. The highest suitability occurred when air temperature seasonality (Bio4) ranged from 6500 to 6900. The highest suitable mean air temperature of the driest quarter ranged from -5 to 0 °C. The highest suitable mean diurnal temperature (Bio2) ranged from 8.9 to 9.7 °C. In future (2041-2060) scenarios, the suitable distribution areas of from high to low are as follows: representative concentration pathway (RCP)26 (6171 km) > RCP45 (6017 km) > RCP80 (4238 km) > RCP60 (2505 km). In future (2061-2080) scenarios, the suitable distribution areas of from high to low are as follows: RCP26 (18,299 km) > RCP60 (11,977 km) > RCP45 (10,354 km) > RCP80 (7539 km). In general, the suitable distribution will increase in the future. The distribution area of will generally be larger under low CO concentrations than under high CO concentrations. This study will facilitate the development of appropriate conservation measures for in the three-river region.
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http://dx.doi.org/10.3390/plants9081015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465144PMC
August 2020

Case report: tracheoesophageal fistula secondary to post-intubation tracheomegaly in a tetanus patient.

Ann Palliat Med 2021 Apr 10;10(4):4922-4925. Epub 2020 Aug 10.

Department of Critical Care Medicine, Maoming People's Hospital, Maoming, China.

Tracheomegaly and tracheoesophageal fistula (TEF) may be complicated within 12-200 days (with a mean of 43 days) of mechanical ventilation but rare in short-term intubation. Here we present a case of TEF secondary to post-intubation tracheomegaly in a tetanus patient. A 49-year-old male was admitted to the emergency room (ER) and diagnosed with tetanus. He became intubated and mechanically ventilated, but showed over-inflation of the endotracheal tube cuff on X-ray and chest computed tomography since the 8th day. After extubation, the patient had severe coughing during eating. Fiberoptic bronchoscopy and gastroscopy demonstrated a TEF located at the anterior wall of the esophagus. Esophageal exclusion and jejunostomy were performed to heal the fistula. The recurrent and uncontrollable muscular rigidity and spasms might be the main cause early tracheomegaly and TEF. Short-term intubation induced TEF should be aware of in specific patients. Both cuff pressure and cuff volume should be monitored to minimize tracheoesophageal injuries in such cases.
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http://dx.doi.org/10.21037/apm-19-681DOI Listing
April 2021

Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients.

Mol Brain 2020 07 8;13(1):102. Epub 2020 Jul 8.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of α-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P < 0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of α-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.
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http://dx.doi.org/10.1186/s13041-020-00637-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346430PMC
July 2020

Experimentally Induced Sepsis Causes Extensive Hypomyelination in the Prefrontal Cortex and Hippocampus in Neonatal Rats.

Neuromolecular Med 2020 09 7;22(3):420-436. Epub 2020 Jul 7.

Department of Critical Care and Emergency, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China.

Neonatal sepsis is associated with cognitive deficit in the later life. Axonal myelination plays a pivotal role in neurotransmission and formation of learning and memory. This study aimed to explore if systemic lipopolysaccharide (LPS) injection would induce hypomyelination in the prefrontal cortex and hippocampus in developing septic neonatal rats. Sprague-Dawley rats (1-day old) were injected with LPS (1 mg/kg) intraperitoneally. By electron microscopy, axonal hypomyelination was evident in the subcortical white matter and hippocampus. The expression of myelin proteins including CNPase, MBP, PLP and MAG was downregulated in both areas of the brain at 7, 14 and 28 days after LPS injection. The frequency of MBP and PLP-positive oligodendrocyte was significantly reduced using in situ hybridization in the cerebral cortex and hippocampus at the corresponding time points after LPS injection, whereas the expression of NG2 and PDGFRα was noticeably increased. In tandem with this was reduction of Olig1 and Olig2 expressions which are involved in differentiation/maturation of OPCs. Expression of NFL, NFM, and NFH was significantly downregulated, indicating that axon development was disrupted after LPS injection. Morris Water Maze behavioral test, Open field test, Rotarod test, and Pole test were used to evaluate neurological behaviors of 28 days rats. The rats in the LPS group showed the impairment of motor coordination, balance, memory, and learning ability and represented bradykinesia and anxiety-like behavior. The present results suggest that following systemic LPS injection, differentiation/maturation of OPCs was affected which may be attributed to the inhibition of transcription factors Olig1 and Olig2 expression resulting in impairment to axonal development. It is suggested that this would ultimately lead to axonal hypomyelination in the prefrontal cortex and hippocampus, which may be associated with neurological deficits in later life.
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http://dx.doi.org/10.1007/s12017-020-08602-6DOI Listing
September 2020

Dihydroquercetin Activates AMPK/Nrf2/HO-1 Signaling in Macrophages and Attenuates Inflammation in LPS-Induced Endotoxemic Mice.

Front Pharmacol 2020 19;11:662. Epub 2020 May 19.

Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, China.

Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia.
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http://dx.doi.org/10.3389/fphar.2020.00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248193PMC
May 2020

HSC70 is required for infectious bursal disease virus (IBDV) infection in DF-1 cells.

Virol J 2020 05 6;17(1):65. Epub 2020 May 6.

Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China.

Background: Infectious bursal disease (IBD) is a highly contagious infectious disease that causes severe immunosuppression and damage to the bursa of Fabricius in chickens. Several proteins involved in IBD virus (IBDV) infection, such as surface immunoglobulin M, integrin, annexin A2 and chicken heat shock protein 90, have been identified. However, the main protein that plays key roles in virus infection has not yet been confirmed.

Methods: DF-1 cell line was transfected with the pcDNA-VP2 plasmid and analyzed by immunofluorescence assay. The proteins reacted with VP2 of IBDV in DF-1 cells were pulldown with the monoclonal antibody and identified by mass spectrometry. Heat shock cognate protein 70 (HSC70), one of these proteins, was selected to be investigated in the function in IBDV infection by specific antibody and its inhibitor.

Results: The DF-1 cell line was transfected with the pcDNA-VP2 plasmid, and expression of IBDV VP2 in DF-1 cells was confirmed by immunofluorescence assays. Heat shock cognate protein 70 (HSC70) was one of the proteins identified by coimmunoprecipitation using a monoclonal antibody (2H11) against VP2 and mass spectrometry analysis. IBDV infection in DF-1 cells was strongly inhibited by both an anti-HSC70 antibody and a HSC70 inhibitor (VER155008).

Conclusion: These results suggest that HSC70 may be an essential factor for IBDV infection.
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http://dx.doi.org/10.1186/s12985-020-01333-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201719PMC
May 2020

New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

Am J Nephrol 2020 29;51(6):453-462. Epub 2020 Apr 29.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis.

Methods: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3.

Results: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48).

Conclusions: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.
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http://dx.doi.org/10.1159/000506664DOI Listing
April 2020

Combining Serum Cystatin C and Urinary N-Acetyl-Beta-D-Glucosaminidase Improves the Precision for Acute Kidney Injury Diagnosis after Resection of Intracranial Space-Occupying Lesions.

Kidney Blood Press Res 2020 10;45(1):142-156. Epub 2020 Jan 10.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China,

Background: Postoperative acute kidney injury (AKI) is frequent and associated with adverse outcomes. Unfortunately, the early diagnosis of AKI remains a challenge. Combining functional and tubular damage biomarkers may provide better precision for AKI detection. However, the diagnostic accuracy of this combination for AKI after neurosurgery is unclear. Serum cystatin C (sCysC) and urinary albumin/creatinine ratio (uACR) are considered functional biomarkers, while urinary N-acetyl-β-D-glucosaminidase (uNAG) represents tubular damage. We aimed to assess the performances of these clinical available biomarkers and their combinations for AKI prediction after resection of intracranial space-occupying lesions.

Methods: A prospective study was conducted, enrolling adults undergoing resection of intracranial space-occupying lesions and admitted to the neurosurgical intensive care unit. The discriminative abilities of postoperative sCysC, uNAG, uACR, and their combinations in predicting AKI were compared using the area under the receiver operating characteristic curve (AUC-ROC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI).

Results: Of 605 enrolled patients, AKI occurred in 67 patients. The cutoff values of sCysC, uNAG, and uACR to predict postoperative AKI were 0.72 mg/L, 19.98 U/g creatinine, and 44.21 mg/g creatinine, respectively. For predicting AKI, the composite of sCysC and uNAG (AUC-ROC = 0.785) outperformed either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). Adding this panel to the predictive model improved the AUC-ROC to 0.808. Moreover, this combination significantly improved risk reclassification over the clinical model alone, with cNRI (0.633) and IDI (0.076). Superior performance of this panel was further confirmed with bootstrap internal validation.

Conclusions: Combination of functional and tubular damage biomarkers improves the predictive accuracy for AKI after resection of intracranial space-occupying lesions.
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http://dx.doi.org/10.1159/000504599DOI Listing
October 2020

Simo decoction versus domperidone suspension for post-pyloric spiral nasoenteric tube placement: A multicenter, randomized, non-inferiority trial.

Clin Nutr 2020 08 12;39(8):2406-2412. Epub 2019 Nov 12.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong, China. Electronic address:

Background & Aims: Leveraging prokinetics to facilitate trans-pyloric migration is a conventional strategy. However, due to restrictions on the use of domperidone suspension, oral prokinetics is relatively modest. The study aims to assess the effectiveness of simo decoction as an alternative to domperidone suspension in facilitating post-pyloric placement of spiral nasoenteric tubes.

Methods: A prospective, open-label, parallel, and non-inferiority randomized controlled trial was performed involving critically ill adults in 6 university hospitals in China between September 2017 and May 2019. Patients were randomly assigned to receive either simo decoction 20 ml q8h, or domperidone suspension 20 mg/20 ml q6h for 24 h. The primary outcome was procedure success defined as post-pyloric placement (spiral nasoenteric tubes reached the first portion of the duodenum or beyond confirmed by abdominal X-ray 24 h after tube insertion).

Results: Of 268 patients assessed for eligibility, 224 patients were enrolled and randomly assigned to the simo decoction group or the domperidone suspension group (n = 112 per group). The success rate of post-pyloric placement was 41.1% (46/112) in the simo decoction group, as compared with 47.3% (53/112) in the domperidone suspension group (a risk difference of -6.3%, 95% CI, -19.2% to 6.7%, adjusted risk difference -3.7%, 95% CI -16.3% to 9.0%), in the intention-to-treat analysis, crossing the prespecified margin of -10% for non-inferiority. There were no differences between groups in the success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond) and proximal jejunum placement, the incidences of any adverse events, length of ICU stay or mortality in ICU.

Conclusions: Non-inferiority of simo decoction to domperidone suspension was not confirmed in facilitating post-pyloric placement of spiral nasoenteric tubes. Registration: The trial was registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn (registration number ChiCTR-INR-17011311).
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http://dx.doi.org/10.1016/j.clnu.2019.11.009DOI Listing
August 2020

[Effect of post-pyloric feeding by spiral nasoenteric tubes on ventilator-associated pneumonia in neurocritical care patients: a retrospective analysis of three clinical randomized controlled trials].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 Aug;31(8):967-971

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510080, Guangdong, China. Corresponding author: Chen Chunbo, Email:

Objective: To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on ventilator-associated pneumonia (VAP) in neurocritical care patients.

Methods: A retrospective study was performed to analyze the clinical data of 175 neurocritical care adult patients with mechanical ventilation (MV) more than 48 hours, who were enrolled in three randomized controlled trials (RCT) conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 to March 2019. The following patient clinical data were collected when patients were enrolled: gender, age, neurologic diagnosis, comorbidities, medication, endotracheal reintubation, bronchoscope treatment, the distal site of nasoenteric tubes, and acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, Glasgow coma scale (GCS) score, and acute gastrointestinal injury (AGI) grade assessed. Patients were divided into VAP group and non-VAP group according to the occurrence of VAP, and the differences of each index between the two groups were compared. Then the influencing factors of P < 0.1 were included in multivariate Logistic regression analysis to identify the potential risk factors affecting the incidence of VAP. Furthermore, patients were divided into gastric feeding group and post-pyloric feeding group according to the distal site of nasoenteric tubes, and subgroup analysis was performed to evaluate the variety of VAP in patients with different tube sites and status.

Results: (1) Forty-two patients occurred VAP in 175 MV patients, and the incidence of VAP was 24.0%. (2) Univariate analysis showed the P value of post-pyloric feeding, APACHE II score, GCS score and bronchoscope treatment were less than 0.1, and post-pyloric feeding and GCS score in VAP group were significantly lower than those in non-VAP group [post-pyloric feeding: 19.0% (8/42) vs. 36.8% (49/133), GCS: 5 (3, 7) vs. 6 (4, 9), both P < 0.05]. Multivariate Logistic regression analysis indicated that post-pyloric feeding was independent protective factor [odds ratio (OR) = 0.360, 95% confidence internal (95%CI) = 0.151-0.857, P = 0.021] and bronchoscope treatment was the independent risk factor (OR = 2.210, 95%CI = 1.051-4.647, P = 0.036) for VAP. (3) The incidence of VAP was 28.8% (34/118), 0% (0/4), 8.3% (1/12), 26.7% (4/15), 22.2% (2/9) and 5.9% (1/17) respectively when tube tip in stomach, D1, D2, D3, D4 and jejunum confirmed by abdominal radiography. Post-pyloric feeding in each proportion seemed to present lower VAP rate compared with gastric feeding, however, no significant difference was found (all P > 0.05). (4) The incidence of VAP in post-pyloric feeding group was significantly lower than that in gastric feeding group [14.0% (8/57) vs. 28.8% (34/118), OR = 0.403, 95%CI = 0.173-0.941, P = 0.032]. Lower VAP rate appeared on patients with SOFA < 12 (OR = 0.392, 95%CI = 0.154-0.995, P = 0.044) and AGI grade ≥ II (OR = 0.086, 95%CI = 0.011-0.705, P = 0.006) fed by post-pyloric route according to the result of subgroup analysis stratified by age, gender, APACHE II score, SOFA score and AGI grade.

Conclusions: Post-pyloric feeding would decrease the incidence of VAP in neurocritical care patients on MV.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.08.011DOI Listing
August 2019

Impact of blood glucose levels on the accuracy of urinary N-acety-β-D-glucosaminidase for acute kidney injury detection in critically ill adults: a multicenter, prospective, observational study.

BMC Nephrol 2019 05 24;20(1):186. Epub 2019 May 24.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, China.

Background: The performance of urinary N-acetyl-β-D-glucosaminidase (uNAG) for the detection of acute kidney injury (AKI) was controversial. uNAG is positively correlated with blood glucose levels. Hyperglycemia is common in the critically ill adults. The influence of blood glucose levels on the accuracy of uNAG in AKI detection has not yet been reported. The present study evaluated the effect of blood glucose levels on the diagnostic accuracy of uNAG to detect AKI.

Methods: A total of 1585 critically ill adults in intensive care units at three university hospitals were recruited in this prospective observational study. uNAG, serum glucose, and glycosylated hemoglobin (HbA1c) were measured at ICU admission. Patients were categorized based on the history of diabetes and blood glucose levels. The performance of uNAG to detect AKI in different groups was assessed by the area under the receiver operator characteristic curve.

Results: Four hundred and twelve patients developed AKI, of which 109 patients were severe AKI. uNAG was significantly correlated with the levels of serum glucose (P < 0.001) and HbA1c (P < 0.001). After stratification based on the serum glucose levels, no significant difference was observed in the AUC of uNAG in detecting AKI between any two groups (P > 0.05). Stratification for stress hyperglycemic demonstrated similar results.However, among non-diabetic patients, the optimal cut-off value of uNAG for detecting AKI was higher in stress hyperglycemic patients as compared to those without stress hyperglycemia.

Conclusions: The blood glucose levels did not significantly affect the performance of uNAG for AKI detection in critically ill adults. However, the optimal cut-off value of uNAG to detect AKIwas affected by stress hyperglycemia in non-diabetic patients.
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http://dx.doi.org/10.1186/s12882-019-1381-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534873PMC
May 2019

Massive air in the heart complicating percutaneous lung biopsy.

Intensive Care Med 2019 10 6;45(10):1476-1477. Epub 2019 May 6.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong, People's Republic of China.

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http://dx.doi.org/10.1007/s00134-019-05623-zDOI Listing
October 2019

The influence of glycemic status on the performance of cystatin C for acute kidney injury detection in the critically ill.

Ren Fail 2019 Nov;41(1):139-149

a The Second School of Clinical Medicine , Southern Medical University , Guangzhou , People's Republic of China.

Objective: Serum cystatin C (sCysC) used clinically for detecting early acute kidney injury (AKI) was reported to be independently associated with hemoglobin (HbA1c) levels, diabetes, and prediabetes. We aimed to assess the influence of HbA1c levels, diabetes, or prediabetes on the performance of sCysC for AKI detection in critically ill adults.

Methods: A prospective observational study was conducted in a mixed medical-surgical intensive care unit (ICU). Patients were divided into four quartiles based on levels of HbA1c or serum glucose at ICU admission, respectively. Additionally, patients were stratified into four subgroups according to HbA1c levels and history of diabetes, namely recognized diabetes (previous diagnosis of diabetes), unrecognized diabetes, prediabetes, and normal glycemic status. Comparisons were made using the area under the receiver operator characteristic curve (AUC) for AKI detection, and reassessed after patient stratification by above-mentioned glycemic status.

Results: Multivariable linear regression revealed that HbA1c levels and history of diabetes were positively related with sCysC (all p < .05). Although stratification for above-mentioned glycemic status displayed no significant difference between AUC of sCysC (all p > .05), sCysC yielded the highest AUCs for detecting AKI in diabetic patients. Moreover, higher optimal cutoff values of sCysC to detect AKI were observed in patients with versus without diabetes.

Conclusion: Glycemic status has no significant impact on the accuracy of sCysC for AKI detection in critically ill adults and a higher optimal cutoff value of sCysC for AKI detection should be considered in diabetic patients.
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http://dx.doi.org/10.1080/0886022X.2019.1586722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450510PMC
November 2019

Evolution and Comprehensive Analysis of DNaseI Hypersensitive Sites in Regulatory Regions of Primate Brain-Related Genes.

Front Genet 2019 7;10:152. Epub 2019 Mar 7.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

How the human brain differs from those of non-human primates is largely unknown and the complex drivers underlying such differences at the genomic level remain unclear. In this study, we selected 243 brain-related genes, based on Gene Ontology, and identified 184,113 DNaseI hypersensitive sites (DHSs) within their regulatory regions. To performed comprehensive evolutionary analyses, we set strict filtering criteria for alignment quality and filtered 39,132 DHSs for inclusion in the investigation and found that 2,397 (~6%) exhibited evidence of accelerated evolution (aceDHSs), which was a much higher proportion that DHSs genome-wide. Target genes predicted to be regulated by brain-aceDHSs were functionally enriched for brain development and exhibited differential expression between human and chimpanzee. Alignments indicated 61 potential human-specific transcription factor binding sites in brain-aceDHSs, including for CTCF, FOXH1, and FOXQ1. Furthermore, based on GWAS, Hi-C, and eQTL data, 16 GWAS SNPs, and 82 eQTL SNPs were in brain-aceDHSs that regulate genes related to brain development or disease. Among these brain-aceDHSs, we confirmed that one enhanced the expression of GPR133, using CRISPR-Cas9 and western blotting. The gene is associated with glioblastoma, indicating that SNPs within DHSs could be related to brain disorders. These findings suggest that brain-related gene regulatory regions are under adaptive evolution and contribute to the differential expression profiles among primates, providing new insights into the genetic basis of brain phenotypes or disorders between humans and other primates.
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http://dx.doi.org/10.3389/fgene.2019.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423895PMC
March 2019

Circular RNA involved in the protective effect of losartan on ischemia and reperfusion induced acute kidney injury in rat model.

Am J Transl Res 2019 15;11(2):1129-1144. Epub 2019 Feb 15.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences 96 Dongchuan Road, Guangzhou 510080, Guangdong Province, PR China.

Although losartan has inhibitory effects on acute kidney injury (AKI), the underlying molecular mechanisms have remained largely unclear. The expressional alteration of circular RNAs (circRNAs) was investigated in the present study to understand the therapeutic effects of losartan against AKI. AKI rat models were established by ischemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined and histological features of kidney tissues examined following hematoxylin and eosin staining. Cell apoptosis was assessed by TUNEL. CircRNA profiles were obtained by RNA-Seq followed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Expression of circRNAs was validated by quantitative RT-PCR. I/R treatment induced an increase in plasma urea and creatinine levels, abnormal kidney tubular structure, and cell apoptosis in Sprague-Dawley (SD) rats, which were effectively inhibited by pre-treatment with losartan. Further RNA-Seq analysis revealed a wide range of differentially expressed circRNAs in I/R rat kidneys, which were reversed by losartan pre-treatment. GO and KEGG analyses revealed that the circRNAs are associated with various biological processes, including the PI3K-Akt signaling pathway. Specifically, circ-Dnmt3a, circ-Akt3, circ-Plekha7, and circ-Me1 were down-regulated in AKI rats and restored by losartan. The current study provides an overview of circRNAs expression profiles based on the inhibitory effects of losartan in ischemic AKI rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413261PMC
February 2019

Rat mRNA expression profiles associated with inhibition of ischemic acute kidney injury by losartan.

Biosci Rep 2019 04 9;39(4). Epub 2019 Apr 9.

Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou 510080, Guangdong Province, P.R. China

: Losartan was reported to inhibit the progression of acute kidney injury (AKI), but little is known about the underlying pharmacological mechanisms. In the present study, the mRNA expression profiles in ischemic AKI rat kidney altered by losartan treatment were analyzed by next-generation deep sequencing technology.: Ischemia and reperfusion treatment was applied to induce AKI in Sprague-Dawley (SD) rats. The urea and creatinine contents in rat blood were measured. H&E staining was performed to evaluate the histological alteration of rat kidney tissues under a microscope. The TUNEL method was applied to analyze apoptosis in rat kidney tissues. The mRNA profiles in rat kidney were analyzed using next-generation deep sequencing. Differential gene expression was confirmed by quantitative qRT-PCR.: The rat model of AKI induced by ischemia and reperfusion showed significant increases in urea and creatinine levels, accompanied by a disrupted kidney tubular structure and renal cell apoptosis. Losartan treatment effectively inhibited the changes in urea and creatinine, tubular structure, and apoptosis in AKI rat kidney. A large number of mRNAs were found to be differentially expressed in the kidneys of AKI rats treated with losartan, which are involved in multiple processes and signaling pathways. The expression of nine differentially expressed genes such as monocyte chemoattractant protein-1 (CCL2) and suppressor of cytokine signaling 3 (SOCS3) was confirmed by qRT-PCR and Western blot.: Losartan caused significant alterations in the gene expression profile in AKI rat kidney, which mediated its anti-AKI effects.
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http://dx.doi.org/10.1042/BSR20181774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454018PMC
April 2019

Is it necessary for all patients to use prokinetic agents to place a trans-pyloric tube?

Intensive Care Med 2019 05 22;45(5):751-752. Epub 2019 Feb 22.

Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, 510080, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1007/s00134-019-05548-7DOI Listing
May 2019