Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

First-principle calculations study of the ORR/OER electrocatalytic activity of ruthenium polyphthalocyanine axially modified with aliphatic thiol groups.

In this study, the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activity of ruthenium polyphthalocyanine axially modified with different aliphatic thiol groups, RuPPc-SR (SR = -SCH3, -SC2H5, -SC3H7, -SC4H9, -SC5H11, and -SC6H13), in an acidic medium were simulated using DFT. All -SR groups can effectively enhance the ORR and OER catalytic activities of RuPPc. The ORR and OER overpotentials of RuPPc-SC4H9 are 0.237 V and 0.436 V, respectively, which are far lower than those of RuPPc (0.960 V and 0.903 V). For RuPPc-SC4H9, the four C and S atoms of the -SC4H9 chain and Ru atom are coplanar, and thus, conjugate effects and inductive effects exist between the -SC4H9 chain and Ru atom. This makes the Ru atom exhibit the least positive Bader charge and smallest spin density, and the anti-bonding orbitals of dxz, dyz, and dz2 of the Ru atom shift below the Fermi level (Ef). This makes the adsorption strength of RuPPc-SC4H9 toward ORR and OER intermediates the weakest, which accelerates the reaction process, thus resulting in better ORR and OER catalytic activity. Therefore, the introduction of the aliphatic thiol groups might effectively improve the OER/ORR catalytic activity of RuPPc.

Scanning the latent phases and superconductivity in the Nb-Pb system at high pressure.

So far, few literature studies have been reported on niobium-lead binary intermetallic compounds, which are expected to have very different properties compared to existing niobium-carbon binary compounds, due to the distinct electronic properties of lead when compared to other carbon-group elements. Herein, we carry out a global structure search for the Nb-Pb system based on the evolutionary algorithm and density functional theory. Based on the dynamical and mechanical stability analyses, we unveiled five new phases, P4/m-Nb9Pb, Cmcm-Nb3Pb, I4/mmm-Nb2Pb, Pmm2-Nb5Pb3, and I4/mmm-NbPb2, that are promising candidates for experimental synthesis. Moreover, the superconducting transitions of all Nb-Pb binary intermetallic compounds are performed with electron-phonon calculations. As Nb9Pb exhibited the maximum Tc in the Nb-Pb intermetallics, greater than 3.0 K at 20 GPa, the phonon band structures, partial phonon density of states (PHDOS), the corresponding Eliashberg spectral functions α2F(ω), and integral electron-phonon coupling (EPC) parameters λ as a function of frequency of Nb9Pb were also studied. This work filled the gap in the pressure-tuned Nb-Pb phase transitions from a systematic first principles study for the first time.

Theoretical Study on ORR/OER Bifunctional Catalytic Activity of Axial Functionalized Iron Polyphthalocyanine.

Designing efficient ORR/OER bifunctional electrocatalysts is very significant for reducing energy consumption and environmental protection. Hence, we studied the ORR/OER bifunctional catalytic activity of iron polyphthalocyanine (FePPc) coordinated by a series of axial ligands which has different electronegative coordination atom (FePPc-L) (L = -CN, -SH, -SCH3, -SC2H5, -I, -Br, -NH2, -Cl, -OCH3, -OH, and -F) in alkaline medium by DFT calculations. Among all FePPc-L, FePPc-CN, FePPc-SH, FePPc-SCH3, and FePPc-SC2H5 exhibit excellent ORR/OER bifunctional catalytic activities. Their ORR/OER overpotential is 0.256 V/0.234 V, 0.278 V/0.256 V, 0.280 V/0.329 V, and 0.290 V/0.316 V, respectively, which are much lower than that of the FePPc (0.483 V/0.834 V). The analysis of the electronic structure of the above catalysts shows that the electronegativity of the coordination atoms in the axial ligand is small, resulting in less distribution of dz2, dyz, and dxz orbitals near Ef, weak orbital polarization, small charge and magnetic moment of the central Fe atom, and weak adsorption strength for *OH. All these prove that the introduction of axial ligands with appropriate electronegativity coordinating atoms can adjust the adsorption of catalyst to intermediates and modify the ORR/OER bifunctional catalytic activities. This is an effective strategy for designing efficient ORR/OER bifunctional electrocatalysts.

CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.

Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-ß, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.

Identification of novel biomarkers for sepsis diagnosis via serum proteomic analysis using iTRAQ-2D-LC-MS/MS.

BACKGROUND: Sepsis is a common cause of morbidity and mortality in the ICU patients. Early diagnosis and appropriate patient management is the key to improve the patient survival and to limit disabilities in sepsis patients. This study was aimed to find new diagnostic biomarkers of sepsis. METHODS: In this study, serum proteomic profiles in sepsis patients by iTRAQ2D-LC-MS/MS. Thirty seven differentially expressed proteins were identified in patients with sepsis, and six proteins including ApoC3, SERPINA1, VCAM1, B2M, GPX3, and ApoE were selected for further verification by ELISA and immunoturbidimetry in 53 patients of non-sepsis, 37 patients of sepsis, and 35 patients of septic shock. Descriptive statistics, functional enrichment analysis, and ROC curve analysis were conducted. RESULTS: The level of ApoC3 was gradually decreased among non-sepsis, sepsis, and septic shock groups (p = 0.049). The levels of VCAM1 (p = 0.010), B2M (p = 0.004), and ApoE (p = 0.039) were showing an increased tread in three groups, with the peak values of B2M and ApoE in the sepsis group. ROC curve analysis for septic diagnosis showed that the areas under ROC curve (AUC) of ApoC3, VCAM1, B2M, and ApoE were 0.625, 0.679, 0.581, and 0.619, respectively, which were lower than that of PCT (AUC 0.717) and CRP (AUC 0.706), but there were no significant differences between each index and PCT or CRP. The combination including four validated indexes and two classical infection indexes for septic diagnosis had the highest AUC-ROC of 0.772. CONCLUSION: Proteins of ApoC3, VCAM1, B2M, and ApoE provide a supplement to classical biomarkers for septic diagnosis.

Understanding the Potential Gene Regulatory Network of Starch Biosynthesis in Tartary Buckwheat by RNA-Seq.

Starch is a major component of crop grains, and its content affects food quality and taste. Tartary buckwheat is a traditional pseudo-cereal used in food as well as medicine. Starch content, granule morphology, and physicochemical properties have been extensively studied in Tartary buckwheat. However, the complex regulatory network related to its starch biosynthesis needs to be elucidated. Here, we performed RNA-seq analyses using seven Tartary buckwheat varieties differing in starch content and combined the RNA-seq data with starch content by weighted correlation network analysis (WGCNA). As a result, 10,873 differentially expressed genes (DEGs) were identified and were functionally clustered to six hierarchical clusters. Fifteen starch biosynthesis genes had higher expression level in seeds. Four trait-specific modules and 3131 hub genes were identified by WGCNA, with the lightcyan and brown modules positively correlated with starch-related traits. Furthermore, two potential gene regulatory networks were proposed, including the co-expression of FtNAC70, FtPUL, and FtGBSS1-3 in the lightcyan module and FtbHLH5, C3H, FtBE2, FtISA3, FtSS3-5, and FtSS1 in the brown. All the above genes were preferentially expressed in seeds, further suggesting their role in seed starch biosynthesis. These results provide crucial guidance for further research on starch biosynthesis and its regulatory network in Tartary buckwheat.

The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing.

BACKGROUND: The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP. METHODS: 32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method. RESULTS: Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47-100%), 88.89% (95% CI 73.49-100%), and 76.54% (95% CI 52.5-100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively. CONCLUSIONS: In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.

Fecal Fusobacterium nucleatum harbored virulence gene fadA are associated with ulcerative colitis and clinical outcomes.

OBJECT: Fusobacterium nucleatum (F.nucleatum), a gram-negative, obligately anaerobe of oral commensal，has been regarded as culprit of periodontal diseases previously and is being unveiled as possible pathogen of gastrointestinal disorders. The key virulence factor of F.nucleatum is FadA adhesin for binding and invading of the host's epithelial cells. Here, we detected fecal F.nucleatum and virulence gene fadA in patients with ulcerative colitis(UC) and evaluated the clinical relevance with UC. METHODS AND SUBJECTS: A total of 310 subjects were enrolled including 100 patients with UC, 70 healthy controls (HC), 70 patients with irritable bowel syndrome subtype diarrhea(IBS-D), and 70 colorectal cancer patients(CRC). Stool samples of UC patients compared with healthy controls as well as IBS-D and CRC patients were collected for Polymerase Chain Reaction(PCR) detection of F.nucleatum (based on 16s rRNA) and virulence gene fadA. RESULTS: The detection rate of 16s rRNA based PCR for F.nucleatum of UC patients(39/100, 39.00%) and CRC(26/70, 37.14%) patients are significantly higher than HC (12/70, 17.14%, P < 0.01) and IBS-D patients (14/70, 20.00%, P < 0.01). Moreover, 19 samples were detected fadA positive from 39 F.nucleatum positive samples of UC patients (19/39, 48.72%), which is significantly higher than HC(2/12, 16.66%, P < 0.05). There were 3 samples detected fadA positive from 14 F.nucleatum positive samples of IBS-D patients(3/14, 21.43%) and 13 out of 26(50.00%) of CRC patients, which were both no significant differences compared with UC patients(21.4% vs 48.72%, P > 0.05; 50.00% vs 48.72%, P > 0.05). For both F.nucleatum and fadA gene positive patients, there were no statistical significances between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells(WBC), and hemoglobin compared with negative patients(defined by either F.nucleatum or fadA negative, or both negative). However, it is worth noting that detection rate of F.nucleatum with virulence gene fadA in patients of severe ulcerative colitis was significantly higher than patients with mild and moderate colitis(28.89% vs 10.91%, P < 0.05). In addition, the fecal F.nucleatum and fadA gene positive patients were more likely to have pancolitis other than left-sided colitis(pancolitis/left-sided colitis: 26.92% vs 10.42%, P < 0.05). CONCLUSIONS: The presence of F.nucleatum and fadA gene increased in UC patients, especially in patients with severe colitis and pancolitis. Strains of F.nucleatum harbored virulence gene fadA are suggested to play a role in the pathogenesis of UC.

Effect of antibiotic therapy in patients with ulcerative colitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Gut microbiota may play a role in the pathogenesis of ulcerative colitis (UC). Antibiotic therapy for patients with UC has shown conflicting results. OBJECTIVES: To evaluate the effect of antibiotic therapy in treating UC. METHODS: PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure (CNKI) databases were searched to identify randomized controlled trials (RCTs) that evaluated antibiotics compared with placebo or no antibiotics in patients with UC. We extracted and pooled the risk ratio (RR). RESULTS: Twelve RCTs were included in this systematic review and meta-analysis, which included 739 patients with active UC. Antibiotic therapy had statistically significant efficacy in inducing remission rate in patients with UC, observed at the end of trials (random-effect RR = 0.77; 95% confidence interval [CI] 0.60 to 0.98, p = .03) or at 12 months after trials (fixed-effect RR = 0.83; 95% CI 0.73 to 0.94, p = .003). CONCLUSIONS: Antibiotic therapy appeared to induce remission more effectively than a placebo or no antibiotic intervention not only in the short-term but also in the long-term for patients with UC. More high-quality clinical trials are needed before clinical recommendations for antibiotic therapy in UC management are made.

Identification and Characterization of Non-Coding RNAs in Thymoma.

BACKGROUND Thymoma is the most common tumor of the anterior mediastinum, and can be caused by infrequent malignancies arising from the epithelial cells of the thymus. Unfortunately, blood-based diagnostic markers are not currently available. High-throughput sequencing technologies, such as RNA-seq with next-generation sequencing, have facilitated the detection and characterization of both coding and non-coding RNAs (ncRNAs), which play significant roles in genomic regulation, transcriptional and post-transcriptional regulation, and imprinting and epigenetic modification. The knowledge about fusion genes and ncRNAs in thymomas is scarce. MATERIAL AND METHODS For this study, we gathered large-scale RNA-seq data belonging to samples from 25 thymomas and 25 healthy thymus specimens and analyzed them to identify fusion genes, lncRNAs, and miRNAs. RESULTS We found 21 fusion genes, including KMT2A-MAML2, HADHB-REEP1, COQ3-CGA, MCM4-SNTB1, and IFT140-ACTN4, as the most frequent and significant in thymomas. We also detected 65 differentially-expressed lncRNAs in thymomas, including AFAP1-AS1, LINC00324, ADAMTS9-AS1, VLDLR-AS1, LINC00968, and NEAT1, that have been validated with the TCGA database. Moreover, we identified 1695 miRNAs from small RNA-seq data that were overexpressed in thymomas. Our network analysis of the lncRNA-mRNA-miRNA regulation axes identified a cluster of miRNAs upregulated in thymomas, that can trigger the expression of target protein-coding genes, and lead to the disruption of several biological pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. CONCLUSIONS Our results show that overexpression of this miRNA cluster activates PI3K-Akt, FoxO, HIF-1, and Rap-1 signaling pathways, suggesting pathway inhibitors may be therapeutic candidates against thymoma.

Advances in the treatment of neuropathic pain with hyperbaric oxygen.

Neuropathic pain (NPP) refers to the pain caused by primary or secondary injury or dysfunction of the peripheral or central nervous system, and usually requires multidisciplinary treatment. However, most pharmacological and non-pharmacological interventions can only temporarily and/or moderately improve pain-related symptoms, and they often produce unbearable adverse reactions or cause drug resistance. Hyperbaric oxygen (HBO2) therapy has been widely used in the clinical treatment of some diseases due to its advantages of safety, few side effects, no resistance, and non-invasiveness. In recent years, increasing numbers of basic and clinical studies have been conducted to investigate the efficacy and mechanism of HBO2 in the treatment of NPP, and great progress has been made in this field. In this paper, we briefly introduce the pathogenesis of NPP and therapeutic effects of HBO2 and summarize the mechanisms underlying the effects of HBO2 in treating NPP, which may provide reference for the clinical treatment of pain with HBO2.

Paper Electrode-Based Flexible Pressure Sensor for Point-of-Care Immunoassay with Digital Multimeter.

A novel paper electrode-based flexible pressure sensor modified with multiwalled carbon nanotubes was designed for point-of-care (POC) immunoassay of carcinoembryonic antigen (CEA) with digital multimeter readout. The portable POC testing device consisted of flexible pressure sensor equipped with a paper electrode and connected through syringe tubing to a single-break microplate. The immunoreaction was initially carried out on the microplate with a sandwich-type assay format using platinum nanozyme-labeled secondary antibody for the gas generation. Upon addition of hydrogen peroxide (H2O2), platinum nanozyme (catalase-like mimic) reduced it into hydrogen oxide and oxygen (O2). The overflowing oxygen gas increased the pressure of the multiwalled carbon nanotube-functionalized paper electrode in a homemade pressure-tight system, and the increased pressure could be readily monitored using the paper electrode-based flexible pressure-tight sensor with a digital multimeter readout. The detectable signal mainly derived from the resistance change of pressure sensor because of its deformation with the assistance of the as-generated gas, and the shift in the resistance could be allowed to detect the gas pressure even as low as 80 Pa. Under optimum conditions, pressure sensor-based immunoassay exhibited good resistance responses toward target CEA within a linear range of 0.5-60 ng/mL at a detection limit of 167 pg/mL. Moreover, our strategy provided acceptable reproducibility, precision, high specificity, and good accordance with the commercial CEA ELISA kit for detecting human serum specimens.

Metal-Polydopamine Framework: An Innovative Signal-Generation Tag for Colorimetric Immunoassay.

In this work, an innovative enzyme-free colorimetric immunoassay was proposed for the sensitive detection of alpha-fetoprotein (AFP) by introducing thymolphthalein-modified metal-polydopamine framework (MPDA@TP) for the signal generation and amplification. Using zeolitic imidazolate framework (ZIF-67) as the template, the hollow-structured metal-polydopamine framework (MPDA) with high surface recovery and abundant groups was synthesized and functionalized with thymolphthalein (TP) molecules via typical π-stacking reaction. In the presence of target AFP, an MPDA@TP-linked immunosorbent assay (MLISA) was implemented on the capture antibody-modified microplate by using detection antibody-labeled MPDA@TP as the secondary antibody. Upon alkaline solution introduction, the coated hydrophobic TP on the MPDA was deprotonated into hydrophilic TP2- ion and dissolved in the solution, thereby resulting in the color change of the solution from nearly colorless to deep blue, and the increasing absorbance of the solution at 595 nm. Importantly, the MPDA@TP-based immunoassay could exhibit high sensitivity for the quantitative detection of target AFP on the basis of the absorbance within a linear range of 10-1000 pg mL-1 at a low detection limit of 2.3 pg mL-1. Furthermore, this system was validated preliminarily to screen human serum specimens with well-matched results for the referenced AFP ELISA kit. Taking advantage of simplicity, enzyme-free, convenience, and sensitivity, MPDA@TP-linked immunosorbent assay has the potential for the application in scientific research and clinical diagnosis.

A new enzyme immunoassay for alpha-fetoprotein in a separate setup coupling an aluminium/Prussian blue-based self-powered electrochromic display with a digital multimeter readout.

A new enzyme immunosensing platform was designed for the simple, rapid and sensitive detection of disease-related biomarkers (alpha-fetoprotein, AFP, was used as a model in this case), coupling an aluminium (Al)/Prussian blue-based self-powered electrochromic display with a digital multimeter readout.

Proteomic Lung Analysis of Mice with Ventilator-Induced Lung Injury (VILI) Using iTRAQ-Based Quantitative Proteomics.

Ventilator-induced lung injury (VILI) has implications for mortality from acute lung injury (ALI) and for acute respiratory distress syndrome (ARDS) patients; the complicated mechanisms of VILI have not been well defined. To discover new biomarkers and mechanisms of VILI, isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-based quantitative proteomics were applied to identify differentially expressed proteins in mice treated with high tidal volume ventilation (HV), low tidal volume ventilation (LV) and lipopolysaccharide (LPS). A total of 14 dysregulated proteins showed the same change trend both in the LV and HV group and no change in the LPS group, and most importantly, the fold change of these proteins increased with the increase of volume ventilation, which indicates these proteins may be considered as potential markers specific for VILI. Ingenuity pathway analysis (IPA) canonical pathways analysis identified the top 4 canonical pathways, including the extrinsic prothrombin activation pathway, coagulation systems, the intrinsic prothrombin activation pathway and the acute phase response, suggesting that these pathways, as associated with these proteins' expression, may be important therapeutic targets for reducing VILI. These findings will provide a new perspective for understanding the pathogenesis of VILI in the future.

Hydroxyethyl starch versus other fluids for non-septic patients in the intensive care unit: a meta-analysis of randomized controlled trials.

INTRODUCTION: Use of hydroxyethyl starch (HES) in septic patients is reported to increase the mortality and incidence of renal replacement therapy (RRT). However, whether or not use of HES would induce the same result in non-septic patients in the intensive care unit (ICU) remains unclear. The objective of this meta-analysis was to evaluate 6% HES versus other fluids for non-septic ICU patients. METHODS: Randomized controlled trials (RCTs) were searched from Pubmed, OvidSP, Embase database and Cochrane Library, published before November, 2013. A meta-analysis was made on the effect of 6% HES versus other fluids for non-septic ICU patients, including mortality, RRT incidence, bleeding volume, red blood cell (RBC) transfusion and fluid application for non-septic patients in ICU. RESULTS: Twenty-two RCTs were included, involving 6,064 non-septic ICU patients. Compared with the other fluids, 6% HES was not associated with decreased overall mortality (RR = 1.03, 95%CI: 0.09 to 1.17; P = 0.67; I(2) = 0). There was no significant difference in RRT incidence, bleeding volume and red blood cell transfusion between 6% HES group and the other fluid groups. However, patients in HES group received less total intravenous fluids than those receiving crystalloids during the first day in ICU (SMD = -0.84; 95%CI: -1.39 to -0.30; P = 0.003, I(2) = 74%). CONCLUSIONS: This meta-analysis found no increased mortality, RRT incidence, bleeding volumes or RBC transfusion in non-septic ICU patients, but the sample sizes were small and the studies generally were of poor quality.

Safety evaluation on low-molecular-weight hydroxyethyl starch for volume expansion therapy in pediatric patients: a meta-analysis of randomized controlled trials.

INTRODUCTION: Hydroxyethyl starch (HES) has been widely used for volume expansion, but its safety in adult patients has been questioned recently. The aim of this meta-analysis is to see whether or not HES has any adverse effect in pediatric patients. METHODS: Randomized controlled trials (RCTs) involving pediatric patients who received 6% low-molecular-weight HES, published before January 2014, were searched for in Pubmed, Embase database and Cochrane Library. Two reviewers independently extracted the valid data, including the mortality, renal function, coagulation, blood loss, hemodynamic changes, and length of hospital and ICU stay. All data were analyzed by I (2)-test, and the results of statistical analysis were displayed in forest plots. Possible publication bias was tested by funnel plots. Bayesian analysis was performed using WinBUGS with fixed and random effects models. RESULTS: A total of 13 RCTs involving 1,156 pediatric patients were finally included in this meta-analysis. Compared with other fluids, HES did not significantly decrease the mortality (RR = -0.01; 95%CI: 0.05 to 0.03; P = 0.54; I(2) = 6%), creatinine level (I(2) -test: MD = 1.81; 95%CI: -0.35 to 3.98; P = 0.10;I(2) = 0%; Bayesian analysis: Fixed effect model MD = 1.77; 95%CI: -0.07 to 3.6; Random effects model MD = 1.78; 95%CI: -1.86 to 5.33), activated partial thromboplastin time (MD = 0.01; 95%CI: -1.05 to 1.07; P = 0.99; I(2) = 42%), and blood loss (MD = 17.72; 95%CI: -41.27 to 5.82; P = 0.10; I(2) = 0%) in pediatric patients. However, HES significantly decreased the blood platelet count (MD = 20.99; 95%CI: -32.08 to -9.90; P = 0.0002; I(2) = 28%) and increased the length of ICU stay (MD = 0.94; 95%CI: 0.18 to 1.70; P = 0.02; I(2) = 46%). CONCLUSIONS: Volume expansion with 6% HES significantly decreased the platelet count and increased the length of ICU stay, also might have an adverse effect on renal function. Therefore HES is not recommended for pediatric patients, which safety needs more high quality RCTs and studies to confirm in future.

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].

OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours. RESULTS: The average disease duration of 7 patients with UC was (9.1 ± 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 ± 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found. CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.

Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.