Enhanced detection of ligand-PPARγ binding based on surface plasmon resonance through complexation with SRC1- or NCOR2-related polypeptide.

A previous study reported the use of a biosensing technique based on surface plasmon resonance (SPR) for the ligand binding detection of peroxisome proliferator activator receptor gamma (PPARγ). This detection was designed based on the structural properties of PPARγ. Because of cross-linked protein inactivation and the low molecular weight of conventional ligands, direct ligand binding detection based on SPR has low stability and repeatability. In this study, we report an indirect response methodology based on SPR technology in which anti-His CM5 chip binds fresh PPARγ every cycle, resulting in more stable detection. We developed a remarkable improvement in ligand-protein binding detectability in vitro by introducing two coregulator-related polypeptides into this system. In parallel, a systematic indirect response methodology can reflect the interaction relationship between ligands and proteins to some extent by detecting the changes in SA-SRC1 and GST-NCOR2 binding to PPARγ. Rosiglitazone, a PPARγ agonist with strong affinity, is a potent insulin-sensitizing agent. Some ligands may be competitively exerted at the same sites of PPARγ (binding rosiglitazone). We demonstrated using indirect response methodology that selective PPARγ modulator (SPPARM) candidates of PPARγ can be found by competing for the binding of the rosiglitazone site on PPARγ, although they may have no effect on polypeptides and PPARγ binding.

Celastrol Stabilizes Glycolipid Metabolism in Hepatic Steatosis by Binding and Regulating the Peroxisome Proliferator-Activated Receptor γ Signaling Pathway.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. Obesity, insulin resistance, and lipid metabolic dysfunction are always accompanied by NAFLD. Celastrol modulates the Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) signaling pathways, thereby promoting lipolysis in 3T3-L1 adipocytes. In the present study, oleic-acid-induced NAFLD and differentiated 3T3-L1 preadipocytes were used as models of NAFLD and obesity to investigate the protective effect of celastrol. We investigated the impact of celastrol on hepatic steatosis caused by oleic acid (OA), as well as the associated underlying molecular pathways. To address the aforementioned questions, we used a cellular approach to analyze the signaling effects of celastrol on various aspects. These factors include the improvement in fatty liver in HepG2 cells, the differentiation of 3T3-L1 preadipocytes, glucose uptake, and the modulation of key transcriptional pathways associated with PPARγ. The administration of celastrol effectively mitigated lipid accumulation caused by OA in HepG2 cells, thereby ameliorating fatty liver conditions. Furthermore, celastrol suppressed the impacts on adipocyte differentiation in 3T3-L1 adipocytes. Additionally, celastrol exhibited the ability to bind to PPARγ and modulate its transcriptional activity. Notably, the ameliorative effects of celastrol on hepatic steatosis were reversed by rosiglitazone. According to our preliminary findings from in vitro celastrol signaling studies, PPARγ is likely to be the direct target of celastrol in regulating hepatic steatosis in HepG2 cells and adipocyte differentiation in 3T3-L1 cells.

Detection of Various Traditional Chinese Medicinal Metabolites as Angiotensin-Converting Enzyme Inhibitors: Molecular Docking, Activity Testing, and Surface Plasmon Resonance Approaches.

Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.

Suitable stocking density of fish in paddy field contributes positively to 2-acetyl-1-pyrroline synthesis in grain and improves rice quality.

BACKGROUND: Fragrant rice is increasingly popular with the public owing to its fresh aroma, and 2-acetyl-1-pyrroline (2-AP) is the main characteristic component of the aroma in fragrant rice. Rice-fish co-culture is an environmentally friendly practice in sustainable agriculture. However, the effect of rice-fish co-culture on 2-AP in grains has received little study. A conventional fragrant rice (Meixiangzhan 2) was used, and a related field experiment during three rice growing seasons was conducted to investigate the effects of rice-fish co-culture on 2-AP, as well as the rice quality, yield, plant nutrients, and precursors and enzyme activities of 2-AP biosynthesis in leaves. This study involved three fish stocking density treatments (i.e. 9000 (D1), 15 000 (D2), and 21 000 (D3) fish fries per hectare) and rice monocropping. RESULTS: Rice-fish co-culture increased the 2-AP content in grains by 2.5-49.4% over that of the monocropping, with significant increases in the early and late rice seasons of 2020. Rice-fish co-culture treatments significantly promoted seed-setting rates by 3.39-7.65%, and improved leaf nutrients and rice quality. Notably, the D2 treatment significantly increased leaf total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents and the head rice rate at maturity stage, while significantly decreased chalkiness degree. There was no significant difference in rice yield. CONCLUSION: Rice-fish co-culture had positive effects on 2-AP synthesis, rice quality, seed-setting rates, and plant nutrient contents. The better stocking density of field fish for rice-fish co-culture in this study was 15 000 fish ha-1 . © 2023 Society of Chemical Industry.

Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis.

BACKGROUND: Previous studies have shown that hydrogen water has antioxidant and anti-inflammatory effects on exercise-induced fatigue; however, its molecular mechanism remains unclear. METHODS: Adult male Sprague-Dawley rats were randomly divided into a pure water drinking group (NC) and a hydrogen water drinking group (HW) (n = 7), and 2-week treadmill training was used to establish a sports model. Gut bacterial community profiling was performed using 16S rRNA gene sequencing analysis. The expression levels of mitochondrial energy metabolism-related genes and the levels of sugar metabolites and enzymes were measured. RESULTS: The exercise tolerance of rats in the HW group significantly improved, and the distribution and diversity of intestinal microbes were altered. Hydrogen significantly upregulated genes related to mitochondrial biogenesis, possibly via the Pparγ/Pgc-1α/Tfam pathway. In addition, hydrogen effectively mediated the reprogramming of skeletal muscle glucose metabolism. CONCLUSION: Our findings establish a critical role for hydrogen in improving endurance exercise performance by promoting mitochondrial biogenesis via the Pparγ/Pgc-1α/Tfam pathway.

Waterlogging tolerance and recovery capability screening in peanut: a comparative analysis of waterlogging effects on physiological traits and yield.

Fifteen peanut varieties at the pod filling stage were exposed to waterlogging stress for 7 days, the enzyme activities and fluorescence parameters were measured after 7 days of waterlogging and drainage. The waterlogging tolerance and recovery capability of varieties were identified. After waterlogging, waterlogging tolerance coefficient (WTC) of relative electrolyte linkage (REL), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity, non-photochemical quenching (NPQ) and photochemical quenching (qL) of leaves of most peanut varieties were increased, while the WTC of the soil and plant analysis development (SPAD) value, PS II actual quantum yield (Φ PS II ), maximum photochemical efficiency (Fv/Fm) were decreased. After drainage, the WTC of REL, MDA content, SOD and CAT activity of leaves were decreased compared with that of after waterlogging, but these indicators of a few cultivars were increased. Φ PS II , Fv/Fm and qL can be used as important indexes to identify waterlogging recovery capability. There was a significant negative correlation between recovery capability and the proportion of reduction in yield, while no significant correlation was found between waterlogging tolerance and the proportion of reduction in yield. Therefore, it is recommended to select varieties with high recovery capability and less pod number reduction under waterlogging in peanut breeding and cultivation.

Application of high-throughput sequencing for hereditary thrombocytopenia in southwestern China.

BACKGROUND: The aim of this study was to design and analyze the applicability of a 21-gene high-throughput sequencing (HTS) panel in the molecular diagnosis of patients with hereditary thrombocytopenia (HT). METHODS: A custom target enrichment library was designed to capture 21 genes known to be associated with HTs. Twenty-four patients with an HT phenotype were studied using this technology. RESULTS: One pathogenic variant on the MYH9 gene and one likely pathogenic variant on the ABCG8 gene previously known to cause HTs were identified. Additionally, 3 previously reported variants affecting WAS, ADAMTS13, and GP1BA were detected, and 9 novel variants affecting FLNA, ITGB3, NBEAL2, MYH9, VWF, and ANKRD26 genes were identified. The 12 variants were classified to be of uncertain significance. CONCLUSION: Our results demonstrate that HTS is an accurate and reliable method of pre-screening patients for variants in known HT-causing genes. With the advantage of distinguishing HT from immune thrombocytopenia, HTS could play a key role in improving the clinical management of patients.

Gualou Xiebai Banxia decoction ameliorates Poloxamer 407-induced hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis. OBJECTIVE: The present study aimed to examine GLXBBX's preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats. MATERIALS AND METHODS: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats' plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected. RESULTS: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1). CONCLUSION: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.

Identifying circRNA- and lncRNA-associated-ceRNA networks in the hippocampi of rats exposed to PM2.5 using RNA-seq analysis.

Non-coding RNAs appear to be involved in the regulation of the nervous system. However, no competing endogenous RNA (ceRNA) network related to PM2.5 damage in the hippocampal function has yet been constructed. Herein, we used whole-transcriptome sequencing technology to systematically study the ceRNA network in rat hippocampi after PM2.5 exposure. We identified 100 circRNAs, 67 lncRNAs, 28 miRNAs, and 539 mRNAs and constructed the most comprehensive ceRNA network to date, to our knowledge. Gene Ontology and KEGG analyses showed that the network molecules are involved in synapses, neural projections, and neural development and involve signal pathways such as the synaptic vesicle cycle. Finally, the expression of the differentially expressed RNAs confirmed by quantitative real-time PCR was consistent with the sequencing data. This study systematically dissected the ceRNA atlas related to cognitive memory function in the hippocampal tissue of PM2.5-exposed rats for the first time, to our knowledge, and promotes the development of potential new treatments for cognitive impairment.

Comparative Characterization of the Complete Mitochondrial Genomes of the Three Apple Snails (Gastropoda: Ampullariidae) and the Phylogenetic Analyses.

The apple snails Pomacea canaliculata, Pomacea diffusa and Pomacea maculate (Gastropoda: Caenogastropoda: Ampullariidae) are invasive pests causing massive economic losses and ecological damage. We sequenced and characterized the complete mitochondrial genomes of these snails to conduct phylogenetic analyses based on comparisons with the mitochondrial protein coding sequences of 47 Caenogastropoda species. The gene arrangements, distribution and content were canonically identical and consistent with typical Mollusca except for the tRNA-Gln absent in P. diffusa. An identifiable control region (d-loop) was absent. Bayesian phylogenetic analysis indicated that all the Ampullariidae species clustered on the same branch. The genus Pomacea clustered together and then with the genus Marisa. The orders Architaenioglossa and Sorbeoconcha clustered together and then with the order Hypsogastropoda. Furthermore, the intergenic and interspecific taxonomic positions were defined. Unexpectedly, Ceraesignum maximum, Dendropoma gregarium, Eualetes tulipa and Thylacodes squamigerus, traditionally classified in order Hypsogastropoda, were isolated from the order Hypsogastropoda in the most external branch of the Bayesian inference tree. The divergence times of the Caenogastropoda indicated that their evolutionary process covered four geological epochs that included the Quaternary, Neogene, Paleogene and Cretaceous periods. This study will facilitate further investigation of species identification to aid in the implementation of effective management and control strategies of these invasive species.

The complete mitochondrial genome of the apple snail Pomacea maculate (Gastropoda: Ampullariidae).

We present the complete mitochondrial genome of Pomacea maculate in this study. The mitochondrial genome is 15,512 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes. Overall nucleotide compositions of the light strand are 41.13% of A, 30.81% of T, 15.25% of C and 12.81% of G. Its gene arrangement and distribution are different from the typical vertebrates. The absence of D-loop is consistent with the Gastropoda, but at least one lengthy non-coding region is essential regulatory element for the initiation of transcription and replication. Phylogenetic tree is constructed by the maximum-likelihood method based on the complete mitochondrial genomes of 15 species of Caenogastropoda, using Helix aspersa as outgroup to assess their actual phylogenetic relationship and evolution. The result provides fundamental data for resolving phylogenetic and genetic problems related to effective management strategies.

Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials.

The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR)=1·04; 95% CI 0·90, 1·19; I(2)=39%; P=0·58), hospital length of stay (HR=1·04; 95% CI 0·83, 1·33; I(2)=57%; P=0·74), treatment failure (relative risk (RR)=0·95; 95% CI 0·79, 1·14; I(2)=20%; P=0·58) or change of antibiotics (RR=1·07; 95% CI 0·79, 1·45; I(2)=44%; P=0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798.

The complete mitochondrial genome of the mudsnail Cipangopaludina cathayensis (Gastropoda: Viviparidae).

We present the complete mitochondrial genome of Cipangopaludina cathayensis in this study. The mitochondrial genome is 17,157 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes. All of them are encoded on the heavy strand except 7 tRNA genes on the light strand. Overall nucleotide compositions of the light strand are 44.51% of A, 26.74% of T, 20.48% of C and 8.28% of G. All the protein-coding genes start with ATG initiation codon except ATP6 with ATA and ND4 with TTG, and 2 types of termination codons are TAA (ATP6, ND2, COX1, COX2, ATP8, ND1, ND6, Cytb, COX3, ND4) and TAG (ND4L, ND5, ND3). There are 29 intergenic spacers and 5 gene overlaps. The tandem repeat sequences are observed in COX2, tRNA(Asp), ATP6, tRNA(Cys), S-rRNA, ND1, Cytb, ND4 and COX3 genes. Gene arrangement and distribution are different from the typical vertebrates. The absence of D-loop is consistent with the Gastropoda, but at least one lengthy non-coding region is essential regulatory element for the initiation of transcription and replication.

The complete mitochondrial genome of the giant African snail Achatina fulica (Mollusca: Achatinidae).

We present the complete mitochondrial genome of the Achatina fulica in this study. The results show that the mitochondrial genome is 15,057 bp in length, which is comprised of 13 protein-coding genes, 2 rRNA genes, 21 tRNA genes. The nucleotide compositions of the light strand are 35.47% of A, 27.97% of T 19.46% of C, and 17.10% of G. Except the ND3, 7 tRNA, ATP6, ATP8, COX3 and 12S-rRNA on the light strand, the rest are encoded on the heavy strand. Five types of inferred initiation codons are ATA (ND1, ND5), GTG (ND6), ATG (COX3, COX2), ATT (ND4) and TTG (COX1, ND2, ND3, ND4L, ATP6, ATP8, Cytb), and 3 types of inferred termination codons are T (COX3, ND2), TAA (ND1, ND4L, ND5, ND6, ATP6), and TAG (ND3, ND4, COX1, COX2, Cytb, ATP8). There are 24 intergenic spacers and 6 gene overlaps. The tandem repeat sequence (total 52 bp) of (AATAATT)n is observed in 16S-rRNA. Gene arrangement and distribution are inconsistent with the typical vertebrates.

The complete mitochondrial genome of the golden apple snail Pomacea canaliculata (Gastropoda: Ampullariidae).

We present the complete mitochondrial genome of Cipangopaludina cathayensis in this study. The mitochondrial genome is 15 706 bp in length, containing 13 protein-coding genes, two rRNA genes and 22 tRNA genes. Overall nucleotide compositions of the light strand are 40.97% of A, 30.78% of T, 20.48% of C and 12.60% of G. Its gene arrangement and distribution are different from the typical vertebrates. The absence of D-loop is consistent with the Gastropoda, but, at least, one lengthy non-coding region is an essential regulatory element for the initiation of transcription and replication. A phylogenetic tree is constructed using the maximum-likelihood method based on the complete mitogenomes of the closely related 21 Gastropoda species to assess their actual phylogenetic relationship and evolution. The result provides fundamental data for resolving phylogenetic and genetic problems related to effective management strategies.

Remote Ischemic Preconditioning Fails to Benefit Pediatric Patients Undergoing Congenital Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

Remote ischemic preconditioning (RIPC) has been proven to reduce the ischemia-reperfusion injury. However, its effect on children receiving congenital cardiac surgery (CCS) was inconsistent. We therefore performed the current meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the effect of RIPC in pediatric patients undergoing CCS.PubMed, Embase, and Cochrane library were searched to identify RCTs assessing the effect of RIPC in pediatric patients undergoing CCS. The outcomes included the duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, postoperative cardiac troponin (cTnI) level, hospital length of stay (HLOS), postoperative inotropic score, and mortality. Subgroup and sensitivity analysis were also performed as predesigned. The meta-analysis was performed with random-effects model despite of heterogeneity. Sensitivity and subgroup analysis were predesigned to identify the robustness of the pooled estimate.Nine RCTs with 697 pediatric patients were included in the meta-analysis. Overall, RIPC failed to alter clinical outcomes of duration of MV (standard mean difference [SMD] -0.03, 95% confidence interval [CI] -0.23-0.17), ICU length of stay (SMD -0.22, 95% CI -0.47-0.04), or HLOS (SMD -0.14, 95% CI -0.55-0.26). Additionally, RIPC could not reduce postoperative cTnI (at 4-6 hours: SMD -0.25, 95% CI -0.73-0.23; P = 0.311; at 20-24 hours: SMD 0.09, 95% CI -0.51-0.68; P = 0.778) or postoperative inotropic score (at 4-6 hours: SMD -0.19, 95% CI -0.51-0.14; P = 0.264; at 24 hours: SMD -0.15, 95% CI -0.49-0.18; P = 0.365).RIPC may have no beneficial effects in children undergoing CCS. However, this finding should be interpreted with caution because of heterogeneity and large-scale RCTs are still needed.

Compression Therapy in the Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis.

Although compression therapy has been widely used after deep vein thrombosis (DVT), its efficacy in prevention of postthrombotic syndrome (PTS) remains disputable. We aimed to update the meta-analysis to comprehensively evaluate the effect of compression therapy on the prevention of PTS in adult patients after DVT.PubMed, Embase, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) evaluating the preventive effect of compression therapy on PTS in adult patients after DVT were included. The primary outcome was the incidence of PTS. All meta-analyses were performed using random-effects models regardless of the heterogeneity. Subgroup and sensitivity analysis were also performed to examine the robustness of the pooled effects according to our predesigned plan. Potential publication bias was assessed.Eight RCTs with 1598 patients were included. Overall, compression therapy could significantly reduce the incidence of PTS (estimate 0.68, 95% confidence interval [CI] 0.52-0.90; P = 0.007). However, it was only associated with a reduction in the incidence of mild/moderate PTS (relative risk [RR] 0.66, 95% CI 0.46-0.93; P = 0.019) but not in the incidence of severe PTS (RR 0.64, 95% CI 0.27-1.50; P = 0.31). Additionally, compression therapy failed to reduce the incidence of recurrent venous thromboembolism (RR 0.91, 95% CI 0.65-1.27; P = 0.58), the incidence of ulceration (RR 0.74, 95% CI 0.36-1.53; P = 0.42), or mortality (RR 0.99, 95% CI 0.72-1.37; P = 0.96). No publication bias was observed.Current evidence still supports compression therapy to be a clinical practice for prophylaxis of PTS in adult patients after DVT. However, our findings should be cautiously interpreted because of heterogeneity and hence more large-scale and well-designed RCTs are still warranted.

Erythropoietin administration for prevention of cardiac surgery-associated acute kidney injury: a meta-analysis of randomized controlled trials.

The effect of erythropoietin (EPO) on the prevention of cardiac surgery-associated acute kidney injury (CSA-AKI) is controversial. Therefore, we undertook the meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of EPO on the prevention of CSA-AKI in adult patients and to explore whether risk factors for AKI could explain the inconsistent effects. PubMed and EMbase databases were searched to identify eligible RCTs. The meta-analysis was performed with fixed- or random-effects models according to the heterogeneity, and the subgroup analysis stratified by risk factors for AKI was carried out. Five RCTs involving 423 patients were included. Overall, EPO administration was not associated with a reduced incidence of CSA-AKI [relative risk (RR): 0.64, 95% confidence interval (CI): 0.35-1.16], with a moderate heterogeneity (I(2) = 67.4%, heterogeneity P = 0.02). Subgroup analysis showed that, in patients without high risk factors for AKI, EPO administration could significantly reduce the incidence of CSA-AKI (RR: 0.38, 95% CI: 0.24-0.61), intensive care unit length of stay [standardized mean difference (SMD): -0.54, 95% CI: -1.05 to -0.04] and hospital length of stay (SMD: -0.48, 95% CI: -0.94 to -0.02). The test of heterogeneity was not significant in the two subgroups. EPO administration could significantly reduce the incidence of CSA-AKI, but not in patients with high risk factors for AKI. Substantial heterogeneity across trials could be attributed to high risk factors for AKI. However, our findings should be interpreted cautiously because of the limited studies included, and high-quality RCTs are warranted.

Sodium bicarbonate in the prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis.

INTRODUCTION: Sodium bicarbonate (SBIC) was reported to be a promising approach to prevent cardiac surgery-associated acute kidney injury (CSA-AKI). However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SBIC on the prevention of CSA-AKI in adult patients undergoing cardiac surgery. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of SBIC versus placebo on the prevention of CSA-AKI in adult patients undergoing cardiac surgery were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was the incidence of CSA-AKI. Meta-analysis was performed using random-effects models. RESULTS: Five RCTs involving 1079 patients were included in the meta-analysis. Overall, compared with placebo, SBIC was not associated with a reduced risk of CSA-AKI (relative risk [RR] 0.99; 95% confidence interval [CI] 0.78 to 1.24; P = 0.911). SBIC failed to alter the clinical outcomes of hospital length of stay (weighted mean difference [WMD] 0.23 days; 95%CI -0.88 to 1.33 days; P = 0.688), renal replacement therapy (RR 0.94; 95%CI 0.49 to 1.82; P = 0.861), hospital mortality (RR 1.37; 95%CI 0.46 to 4.13; P = 0.572), postoperative atrial fibrillation (RR 1.02; 95%CI 0.65 to 1.61; P = 0.915). However, SBIC was associated with significant increased risks in longer duration of ventilation (WMD 0.64 hours; 95%CI 0.16 to 1.11 hours; P = 0.008), longer ICU length of stay (WMD 2.06 days; 95%CI 0.54 to 3.58 days; P = 0.008), and increased incidence of alkalemia (RR 2.21; 95%CI 1.42 to 3.42; P <0.001). CONCLUSIONS: SBIC could not reduce the incidence of CSA-AKI. Contrarily, SBIC prolongs the duration of ventilation and ICU length of stay, and increases the risk of alkalemia. Thus, SBIC should not be recommended for the prevention of CSA-AKI and perioperative SBIC infusion should be administrated with caution.