Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I.

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, the impact of the virus on glucose metabolism in host cells and the subsequent effects are still unknown. Here, glycolysis induced by SVA is shown to facilitate virus replication by promoting lactate production, which then attenuates the interaction between the mitochondrial antiviral-signaling protein (MAVS) and retinoic acid-inducible gene I (RIG-I). SVA induces glycolysis in PK-15 cells, as indicated by significantly increased expression of hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate kinase 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), and superoxide dismutase-2 (SOD2) in a dose-and replication-dependent manner, and enhanced lactate production, while reducing ATP generation. Overexpression of PKM, PGK1, HIF-1α, and PDK3 in PK-15 cells and high glucose concentrations promote SVA replication, while glycolytic inhibitors decrease it. Inhibition of RLR signaling allowed better replication of SVA by promoting lactate production to attenuate the interaction between MAVS and RIG-I, and regulatory effect of glycolysis on replication of SVA was mainly via RIG-I signaling. SVA infection in mice increased expression of PKM and PGK1 in tissues and serum yields of lactate. Mice treated with high glucose and administered sodium lactate showed elevated lactate levels and better SVA replication, as well as suppressed induction of RIG-I, interferon beta (IFNß), IFNα, interferon-stimulated gene 15 (ISG15), and interleukin 6 (IL-6). The inhibitory effect on interferons was lower in mice administered sodium oxamate and low glucose compared to the high glucose, indicating that RLR signaling was inhibited by SVA infection through lactate in vitro and in vivo. These results provide a new perspective on the relationship between metabolism and innate immunity of the host in SVA infection, suggesting that glycolysis or lactate may be new targets against the virus.

Synthesis of Carboranylated Dihydropyrrolo[1,2-a]quinoxalines and Dihydroindolo[1,2-a]quinoxalines by BF3·OEt2-Catalyzed Heterocyclization of C-Formyl-o-carboranes and Investigation of Their Oxidation Stability.

A BF3·OEt2-catalyzed synthesis of carboranylated dihydropyrrolo[1,2-a]quinoxalines and dihydroindolo[1,2-a]quinoxalines in 30-99% yields is presented through the heterocyclization of various C-modified C-formyl-o-carboranes with 1-(2-aminophenyl)-pyrroles/indoles. A systematic comparative investigation of their oxidation stability in air confirmed that 4-carboranyl-4,5-dihydropyrrolo[1,2-a]quinoxaline had better stability than the 4-phenyl analogue. A cage-deboronation reaction for N-acetyl-substituted carboranylated dihydropyrrolo[1,2-a]quinoxaline produced the corresponding 7,8-nido-carborane cesium salt. A kinetic resolution was also realized to obtain an optically pure carboranylated N-heterocycle scaffold bearing a carborane cage carbon-bonded chiral stereocenter.

Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease.

OBJECTIVE: The primary objective of this study was to investigate potential mechanisms and explore hub genes of craniofacial microsomia (CFM) patients associated with congenital heart defects (CHD). METHODS: Initially, the authors acquired target gene data related to CFM and congenital cardiac anomalies. Subsequently, the authors established a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were conducted using Metascape. Finally, the authors hub genes were screened by the cytoHubba plugin. RESULTS: A total of 43 CFM genes and 120 optimal CHD candidate genes were selected. The PPI networks for pathogenic genes contained 163 nodes and 1179 edges. Functional enrichment analysis largely focused on tissue formation and development. Five modules were identified from the PPI network, and 7 hub genes were screened out. The genes most relevant to CFM associated with congenital cardiac anomalies pathogenesis included fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.

Metabolic profiles in the xylem sap of Brassica juncea exposed to cadmium.

Metabolic profiles in xylem sap are considered a fundamental mechanism for Cadmium (Cd) detoxification in plants. However, the metabolic mechanism of Brassica juncea xylem sap in response to Cd is still unclear. Here, we investigated the effects on the metabolomics of B. juncea xylem sap treated with Cd at different times by utilizing a nontargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics method for further elucidating the response mechanism of Cd exposure. The findings indicated that 48 h and 7 days Cd exposure caused significant differences in metabolic profiles of the B. juncea xylem sap. Those differential metabolites are primarily involved in amino acids, organic acids, lipids, and carbohydrates, and most of them were downregulated, which played essential roles in response to Cd stress. Furthermore, B. juncea xylem sap resisted 48-h Cd exposure via regulation of glycerophospholipid metabolism, carbon metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, linoleic acid metabolism, C5-branched dibasic acid metabolism, alpha-linolenic acid metabolism, cyanoamino acid metabolism, ABC transporters, biosynthesis of amino acids, and pyrimidine metabolism; whereas alpha-linolenic acid metabolism, glycerophospholipid metabolism, photosynthesis, and oxidative phosphorylation were regulated for resisting 7-day Cd exposure.

Online Multi-Label Streaming Feature Selection Based on Label Group Correlation and Feature Interaction.

Multi-label streaming feature selection has received widespread attention in recent years because the dynamic acquisition of features is more in line with the needs of practical application scenarios. Most previous methods either assume that the labels are independent of each other, or, although label correlation is explored, the relationship between related labels and features is difficult to understand or specify. In real applications, both situations may occur where the labels are correlated and the features may belong specifically to some labels. Moreover, these methods treat features individually without considering the interaction between features. Based on this, we present a novel online streaming feature selection method based on label group correlation and feature interaction (OSLGC). In our design, we first divide labels into multiple groups with the help of graph theory. Then, we integrate label weight and mutual information to accurately quantify the relationships between features under different label groups. Subsequently, a novel feature selection framework using sliding windows is designed, including online feature relevance analysis and online feature interaction analysis. Experiments on ten datasets show that the proposed method outperforms some mature MFS algorithms in terms of predictive performance, statistical analysis, stability analysis, and ablation experiments.

The elemental defense effect of cadmium on Alternaria brassicicola in Brassica juncea.

BACKGROUND: The elemental defense hypothesis states a new defensive strategy that hyperaccumulators defense against herbivores or pathogens attacks by accumulating heavy metals. Brassica juncea has an excellent ability of cadmium (Cd) accumulation. However, the elemental defense effect and its regulation mechanism in B. juncea remain unclear. RESULTS: In this study, we profiled the elemental defense effect and the molecular regulatory mechanism in Cd-accumulated B. juncea after Alternaria brassicicola infection. B. juncea treated with 180 mg Kg- 1 DW CdCl2 2.5H2O exhibited obvious elemental defense effect after 72 h of infection with A. brassicicola. The expression of some defense-related genes including BjNPR1, BjPR12, BjPR2, and stress-related miRNAs (miR156, miR397, miR398a, miR398b/c, miR408, miR395a, miR395b, miR396a, and miR396b) were remarkably elevated during elemental defense in B. juncea. CONCLUSIONS: The results indicate that Cd-accumulated B. juncea may defend against pathogens by coordinating salicylic acid (SA) and jasmonic acid (JA) mediated systemic acquired resistance (SAR) and elemental defense in a synergistic joint effect. Furthermore, the expression of miRNAs related to heavy metal stress response and disease resistance may regulate the balance between pathogen defense and heavy metal stress-responsive in B. juncea. The findings provide experimental evidence for the elemental defense hypothesis in plants from the perspectives of phytohormones, defense-related genes, and miRNAs.

Effect of Rosuvastatin on Myocardial Apoptosis in HypertensiveRats Through SIRT1/NF-κB Signaling Pathway.

The study aimed to observe the effect of rosuvastatin on myocardial apoptosis in hypertensive rats through the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. The spontaneously hypertensive rat (SHR) model was established, and the rats were randomly divided into the SHR group, Rosuvastatin group and Control group. The blood pressure, creatine kinase (CK) and other myocardial indexes in each group were detected, the cardiac function indexes of rats were determined using magnetic resonance imaging (MRI) and echocardiography (ECG), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in myocardial tissues were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis level of myocardial tissues was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the expression levels of the SIRT1/NF-κB signaling pathway and apoptosis genes and proteins in myocardial tissues in each group were detected via quantitative polymerase chain reaction (qPCR) and Western blotting. In the SHR group, the blood pressure, the levels of serum creatinine (CR) and CK were increased (p<0.05). In the SHR group, both fractional shortening (FS%) and ejection fraction (EF%) were obviously lower than those in the control group (p<0.05), while both left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were higher than those in the control group (p<0.05), and the levels of TNF-α, IL-6 and myeloperoxidase (MPO) were increased (p<0.05). The number of apoptotic cells in myocardial tissues in the SHR group was larger than that in the other two groups (p<0.05). In the SHR group, the expression levels of Caspase3 and NF-κB were remarkably higher than those in the Rosuvastatin group (p<0.05), while the expression levels of Bcl-2 and SIRT1 were remarkably lower than those in the Rosuvastatin group (p<0.05). Rosuvastatin can inhibit myocardial apoptosis in hypertensive rats through up-regulating SIRT1 and down-regulating NF-κB.

Fast Approximation for Sparse Coding with Applications to Object Recognition.

Sparse Coding (SC) has been widely studied and shown its superiority in the fields of signal processing, statistics, and machine learning. However, due to the high computational cost of the optimization algorithms required to compute the sparse feature, the applicability of SC to real-time object recognition tasks is limited. Many deep neural networks have been constructed to low fast estimate the sparse feature with the help of a large number of training samples, which is not suitable for small-scale datasets. Therefore, this work presents a simple and efficient fast approximation method for SC, in which a special single-hidden-layer neural network (SLNNs) is constructed to perform the approximation task, and the optimal sparse features of training samples exactly computed by sparse coding algorithm are used as ground truth to train the SLNNs. After training, the proposed SLNNs can quickly estimate sparse features for testing samples. Ten benchmark data sets taken from UCI databases and two face image datasets are used for experiment, and the low root mean square error (RMSE) results between the approximated sparse features and the optimal ones have verified the approximation performance of this proposed method. Furthermore, the recognition results demonstrate that the proposed method can effectively reduce the computational time of testing process while maintaining the recognition performance, and outperforms several state-of-the-art fast approximation sparse coding methods, as well as the exact sparse coding algorithms.

Bone marrow mesenchymal stem cells regulate TGF-ß to adjust neuroinflammation in postoperative central inflammatory mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is one of the common postoperative complications, which is more common in aged patients. POCD mainly manifests as cognitive function changes after surgery, such as memory decline and inattention. In some severe cases, patients may suffer from personality changes and (or) social behavior decline. The aim of the current study is to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in postoperative central inflammatory mice. METHODS: Mice were randomly assigned to four groups: sham, sham+BMSCs, model, and BMSCs group. In the model group, mice were intraperitoneally injected 8 mg/kg per day lipopolysaccharide for 5 days. In sham+BMSCs and BMSCs group, BMSCs (1 × 10 7 ) in 100 µL saline were injected into sham mice and model mice, respectively. RESULTS: In the model group, transforming growth factor ß (TGF-ß) protein expression was significantly increased, compared with that in the sham group. BMSCs were treated into postoperative central inflammatory mice, which resulted in a decreased of TGF-ß protein expression. TGF-ß and smad2 protein expression were suppressed, and apoptosis rate and inflammation were inhibited in coculture with BMSCs. The suppression of TGF-ß inhibited the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. The promotion of TGF-ß reduced the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. CONCLUSION: The present study demonstrates that BMSCs regulates TGF-ß to adjust neuroinflammation in postoperative central inflammatory mice.

Metal-Free Intramolecular Aminophosphination of Allenes.

A metal-free intramolecular aminophosphination of sulfonamidoallenes with diarylphosphine oxides and Tf2O was developed. This method offers a general and practical procedure to construct valuable alkenylphosphine-substituted N-heterocycles via the bifunctionalization reaction of allenes in good yields under mild conditions.

Bidirectional interactions between curcumin and gut microbiota in transgenic mice with Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions: (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as Bacteroidaceae, Prevotellaceae, Lactobacillaceae, and Rikenellaceae at family level, and Prevotella, Bacteroides, and Parabacteroides at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.

mPGES-1-Derived PGE2 Contributes to Indoxyl Sulfate-Induced Mesangial Cell Proliferation.

BACKGROUND/AIMS: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. METHODS: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins. In another experimental setting, PGE2 was applied to the MCs to examine its direct effect on MC proliferation, as well as the regulation of prostaglandin E receptors (EPs) by qRT-PCR. RESULTS: With the administration of IS, mPGES-1(not mPGES-2 and cytosolic PGES) was significantly upregulated at both protein and mRNA levels in line with a promoted MC proliferation. Interestingly, silencing mPGES-1 reduced cell number in S and G2 phases and blocked the upregulation of cyclin A2 and cyclin D1 in parallel with blunted PGE2 release after IS treatment, indicating that mPGES-1-derived PGE2 could contribute to MC proliferation. Furthermore, we confirmed that exogenous PGE2 could directly trigger the proliferative response in MCs. Lastly, we observed a selective upregulation of EP2 after PGE2 treatment and enhanced phosphorylation of NF-κB following IS administration in MCs, suggesting the potential involvements of EP2 and NF-κB in this pathological process. CONCLUSION: mPGES-1-derived PGE2 contributed to IS-induced mesangial cell proliferation.

miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1.

Environmental carcinogens-induced lung cancer and potential mechanisms have attracted widespread attention. Currently, microRNAs (miRNAs) have been recognized as key players in development of cancer, among which guide strand of miRNA has been well documented rather than its passenger strand (miRNA*). Our previous study showed that treatment of 0.1 nM AFB1 for 50 passages could induce malignant transformation of immortalized human bronchial epithelial cells stably expressing CYP2A13 (P50 B-2A13 cells). However, the role of miRNAs in this carcinogenic proceeding is still unclear. In present study, 36 upregulated and 27 downregulated miRNAs in P50 B-2A13 cells were first identified by miRNA microarray, and miR-138-1* was selected as a candidate miRNA by RT-qPCR and pilot experiments. Functional studies revealed that miR-138-1* could inhibit proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Further, target analysis and dual-luciferase reporter gene assay identified that miR-138-1(*) was consequentially paired with 3'-UTR of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and decreased the luciferase activity. miR-138-1* could decrease the expressions of PDK1 and its downstream proteins in PI3K/PDK/Akt pathway but not vice versa, indicating that miR-138-1* might affect AFB1-induced malignant transformation through targeting PDK1. As predicted, interference of PDK1 showed the similar effects to miR-138-1* in the proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Our study demonstrated that miR-138-1* played a critical role in AFB-induced malignant transformation of B-2A13 cells by targeting PDK1. Still, the study provides a novel insight into the roles of miRNA* during carcinogenesis, particularly airborne carcinogens-induced lung cancer.

Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2.

Indoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investigate the role of IS in modulating mesangial cell (MC) proliferation and the underlying mechanism. The proliferation of MCs induced by IS was determined by cell number counting, DNA synthase rate, and cell cycle phase analysis. COX-2 expression was examined by Western blotting and qRT-PCR, and a specific COX-2 inhibitor NS398 was applied to define its role in IS-induced MC proliferation. Following IS treatment, MCs exhibited increased total cell number, DNA synthesis rate, and number of cells in S and G2 phases paralleled with the upregulation of cyclin A2 and cyclin D1. Next, we found an inducible inflammation-related enzyme COX-2 was remarkably enhanced by IS, and the inhibition of COX-2 by NS398 significantly blocked IS-induced MC proliferation in line with a blockade of PGE2 production. These findings indicated that IS could induce MC proliferation via a COX-2-mediated mechanism, providing new insights into the understanding and therapies of progressive loss of RRF in ESRD.

Development and Characterization of Novel EST-SSRs from Larix gmelinii and Their Cross-Species Transferability.

A set of 899 L. gmelinii expression sequence tags (ESTs), available at the National Center of Biotechnology Information (NCBI), was employed to address the feasibility on development of simple sequence repeat (SSR) markers for Larch species. Totally, 634 non-redundant unigenes including 145 contigs and 489 singletons were finally identified and mainly involved in biosynthetic, metabolic processes and response to stress according to BLASTX results, gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) maps. Approximately 11.7% (74) unigenes contained 90 candidate SSRs, which were mainly trinucleotides (29, 32.2%) and dinucleotides (26, 28.9%). A relatively high frequency of SSRs was respectively found in the Open Reading Frame (ORF, about 54.4%) and 5'-untranslated region (5'-UTR, 31.2%), while a low frequency was observed in the 3'-untranslated region (3'-UTR, about 14.4%). Of the 45 novel EST-SSRs markers, nine were found to be polymorphic at two L. gmelinii populations. The number of alleles per locus (Na) ranged from two to four, and the observed (Ho) and expected (He) heterozygosity values were 0.200-0.733 and 0.408-0.604, respectively. The inbreeding coefficients (FIS) for all loci were more than zero except Lg41. Most of these 9EST-SSR markers were transferable to its related species L. kaempferi, L. principis-rupprechtii and L. olgensis. These novel EST-SSRs will be useful for further research on comparative genomics, genetic resources conservation and molecular breeding in larch trees.

Mitochondrial DNA-Activated cGAS-STING Signaling in Environmental Dry Eye.

Purpose: The cGAS-STING pathway has been shown to be an important mediator of inflammation. There is emerging evidence of the importance of this signaling cascade in a variety of inflammatory diseases settings. Here, we present evidence that the mitochondrial DNA (mtDNA) damage-mediated cGAS-STING pathway plays an important role in the induction of inflammation in environmental dry eye (DE). Methods: RT-qPCR and Western blot were used to assess the induction of the cGAS-STING pathway and inflammatory cytokines in environmental DE mouse model, primary human corneal epithelial cells (pHCECs), and patients with DE. RNA sequencing was used to determine mRNA expression patterns of high osmotic pressure (HOP)-stimulated pHCECs. mtDNA was detected with electron microscopy, flow cytometry, and immunofluorescent staining. mtDNA was isolated and transfected into pHCECs for evaluating the activation of the cGAS-STING pathway. Results: The expression levels of cGAS, STING, TBK1, IRF3, and IFNß were significantly increased in an environmental DE model and HOP-stimulated pHCECs. The STING inhibitor decreased the expression of inflammatory factors in DE. An upregulation of STING-mediated immune responses and IRF3 expression mediated by TBK1 were observed in the HOP group. HOP stimulation induced mitochondrial oxidative damage and the leakage of mtDNA into the cytoplasm. Then, mtDNA activated the cGAS-STING pathway and induced intracytoplasmic STING translocated to the Golgi apparatus. Finally, we also found activated cGAS-STING signaling in the human conjunctival blot cell of patients with DE. Conclusions: Our findings suggest that the cGAS-STING pathway is activated by recognizing cytoplasmic mtDNA leading to STING translocation, further exacerbating the development of inflammation in environmental DE.

CD46 inhibits the replication of swine influenza viruses by promoting the production of type I IFNs in PK-15 cells.

Swine flu caused by swine influenza A virus (swIAV) is an acute respiratory viral disease that is spreading in swine herds worldwide. Although the effect of some host factors on replication of swIAV has been identified, the role of CD46 in this process is unclear. Here, we report that CD46 inhibits the replication of swIAV by promoting the production of type I interferons (IFNs) in porcine kidney (PK-15) cells. CD46 knockout (CD46-KO) and stably expressing (CD46-overexpression) PK-15 cells were prepared using lentivirus-mediated CRISPR/Cas9 gene editing and seamless cloning technology. The results of virus infection in CD46-overexpression PK-15 cells showed that the replication of H1N1 and H3N2 swIAVs were inhibited, and the production of type I IFNs (IFN-α, IFN-ß), interferon regulatory factor (IRF) 3, and mitochondrial antiviral-signaling protein (MAVS) was enhanced. Virus infection in CD46-KO PK-15 cells showed the opposite results. Further results showed that CD46-KO PK-15 cells have a favorable ability to proliferate influenza viruses compared to Madin-Darby canine kidney (MDCK) and PK-15 cells. These findings indicate that CD46 acts as promising target regulating the replication of swIAV, and help to develop new agents against infection and replication of the virus.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

OBJECTIVE: To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. METHODS: Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. RESULTS: Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. CONCLUSION: Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

Antibiotic resistance in Pseudomonas aeruginosa is associated with decreased fitness.

The number of clinical specimens containing ß-lactam-resistant Pseudomonas aeruginosa isolates is increasing. However, whether resistance is associated with reduced fitness is still uncertain in clinical Pseudomonas aeruginosa isolates. In this study, we aimed to determine whether ß-lactam resistance conferred a fitness cost in Pseudomonas aeruginosa. Growth rate, extracellular slime production, elastase activity, proteolytic activity, LasA protease activity, biofilm formation, and pairwise in vitro competition experiments were investigated in a collection of 11 isogenic, ß-lactam-susceptible and -resistant (≥8-fold increase in minimum inhibitory concentration (MIC)) pairs of P. aeruginosa clinical isolates; each pair was recovered from a different patient treated with ß-lactam antibiotics. All ß-lactam-resistant Pseudomonas aeruginosa isolates showed a significant reduction in elastase activity. In addition, 90.9% (10/11) of ß-lactam-resistant Pseudomonas aeruginosa isolates were associated with markedly lower growth rate and proteolytic activity, and 81.8% (9/11) of ß-lactam-resistant Pseudomonas aeruginosa isolates had less extracellular slime production, compared to susceptible isolates. Meanwhile, LasA protease activity and biofilm formation ability were variable among isolates. Pairwise in vitro competition experiments showed that 72.7% (8/11) of ß- lactam-susceptible strains could outgrow resistant strains. In conclusion, resistance development with ß-lactam exposure confers a fitness cost, resulting in a decreased invasion potential, while the effect on viability varied. Thus, the potential for the dissemination of ß-lactam-resistant Pseudomonas aeruginosa clinical isolates should not be underestimated.