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Coronavirus disease 2019 (COVID-19) is raging worldwide and causes an immense disease burden. Despite this, the biomarkers and targeting drugs of COVID-19 of differing severity remain largely unknown. Based on the GSE164805 dataset, we identified modules most critical for mild COVID-19 (mCOVID-19) and severe COVID-19 (sCOVID-19) through WGCNA, respectively. We subsequently constructed a protein–protein interaction network, and detected 16 hub genes for mCOVID-19 and 10 hub genes for sCOVID-19, followed by the prediction of upstream transcription factors (TFs) and kinases. The enrichment analysis then showed downregulation of TNFA signaling via NFKB for mCOVID-19, as well as downregulation of MYC targets V1 for sCOVID-19. Infiltration degrees of many immune cells, such as macrophages, were also sharply different between mCOVID-19 and sCOVID-19 samples. Predicted protein targeting drugs with the highest scores nearly all belong to naturally derived or synthetic glucocorticoids. For the two single-cell RNA-seq datasets, we explored the expression distribution of hub genes for mCOVID-19/sCOVID-19 in each cell type. The expression levels of PRKCA, MCM5, TYMS, RBBP4, BCL6, FLOT1, KDM6B, and TLR2 were found to be cell-type-specific. Furthermore, the expression levels of 10 hub genes for mCOVID-19 were significantly upregulated in PBMCs between eight healthy controls and eight mCOVID-19 patients at our institution. Collectively, we detected critical modules, pathways, TFs, kinases, immune cells, targeting drugs, hub genes, and their expression distributions in different cell types that may involve the pathogenesis of COVID-19 of differing severity, which may propel earlier diagnosis and more effective treatment of this intractable disease in the future. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that respiratory tract microecological disorders may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Understanding the composition of the respiratory microbiome in COPD and its relevance to respiratory immunity will help develop microbiome-based diagnostic and therapeutic approaches. One hundred longitudinal sputum samples from 35 subjects with acute exacerbation of COPD (AECOPD) were analysed for respiratory bacterial microbiome using 16S ribosomal RNA amplicon sequencing technology, and the sputum supernatant was analysed for 12 cytokines using a Luminex liquid suspension chip. Unsupervised hierarchical clustering was employed to evaluate the existence of distinct microbial clusters. In AECOPD, the respiratory microbial diversity decreased, and the community composition changed significantly. The abundances of Haemophilus, Moraxella, Klebsiella, and Pseudomonas increased significantly. Significant positive correlations between the abundance of Pseudomonas and TNF-α, abundance of Klebsiella and the percentage of eosinophils were observed. Furthermore, COPD can be divided into four clusters based on the respiratory microbiome. AECOPD-related cluster was characterized by the enrichment of Pseudomonas and Haemophilus and a high level of TNF-α. Lactobacillus and Veillonella are enriched in therapy-related phenotypes and may play potential probiotic roles. There are two inflammatory endotypes in the stable state: Gemella is associated with the Th2 inflammatory endotypes, whereas Prevotella is associated with the Th17 inflammatory endotypes. Nevertheless, no differences in clinical manifestations were found between these two endotypes. The sputum microbiome is associated with the disease status of COPD, allowing us to distinguish different inflammatory endotypes. Targeted anti-inflammatory and anti-infective therapies may improve the long-term prognosis of COPD. [ABSTRACT FROM AUTHOR]

Epstein Barr virus positive (EBV+) immunodeficiency-associated lymphoproliferative disorders (IA-LPD) are heterogeneous diseases with variable treatment strategies that are not well-defined. A 68-year-old woman with systemic lupus erythematosus developed EBV+ B-cell polymorphic lymphoproliferative disease (LPD). Positron emission tomography computed tomography (PET/CT) showed a large nasopharyngeal mass, multiple pulmonary lesions, splenomegaly and disseminated lymphadenopathy. Plasma EBV DNA was grossly elevated to 1.5 × 104 IU/mL. There were three paraproteins. Treatment with O-CHOP (obinutuzumab, cyclophosphamide, adriamycin, vincristine, prednisolone) led to undetectable plasma EBV DNA, suggesting eradiation of the EBV-positive malignant clone. However, radiologic abnormalities were still present on PET/CT, and paraprotein persisted. A nasopharyngeal re-biopsy showed infiltration with EBV-negative plasma cells. On treatment with lenalidomide, she finally achieved complete metabolic response. Molecular analysis showed that the EBV+ B-cell LPD and the EBV– plasma cell lesion exhibited identical immunoglobulin gene rearrangements. Next generation sequencing revealed that the EBV+ B-LPD showed mutation in only one gene (TP53), a profile typical of EBV-driven lymphoid neoplasms. However, the EBV– plasma cell lesion showed mutations in five genes (TP53, SF3B1, STAT5B, CD79B and CRKL), suggesting that these mutations instead of EBV infection were the oncogenic driver. The presence of both EBV+ and EBV– lesions, which showed different mutational profiles, indicated clonal heterogeneity that might be of biologic and therapeutic significance. [ABSTRACT FROM AUTHOR]

Microsporum gypseum causes dermatomycoses in giant pandas (Ailuropoda melanoleuca). This study aimed to investigate the immune response of M. gypseum following deep infection. The degree of damage to the heart, liver, spleen, lungs, and kidneys was evaluated using tissue fungal load, organ index, and histopathological methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) detected the mRNA expression of receptors and cytokines in the lung, and immunofluorescence staining and flow cytometry, were used to assess immune cells in the lung. The results indicated that conidia mainly colonized the lungs and caused serious injury with M. gypseum infection. Furthermore, dectin-1, TLR-2, and TLR-4 played a role in recognizing M. gypseum cells. Numerous inflammatory cells, mainly macrophages, dendritic cells, polymorphonuclear neutrophils, and inflammatory cytokines (TGF-β, TNF-α, IL-1β, IL-6, IL-10, IL-12, and IL-23), were activated in the early stages of infection. With the high expression of IL-22, IL-17A, and IL-17F, the Th17 pathway exerted an adaptive immune response to M. gypseum infection. These results can potentially aid in the diagnosis and treatment of diseases caused by M. gypseum in giant pandas. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI. METHODS In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite allcause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. RESULTS A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001). CONCLUSIONS For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus-positive diffuse large B-cell lymphoma after frontline brentuximab vedotin treatment of classical Hodgkin lymphoma Right axillary lymph node biopsy showed mixed cellularity classical Hodgkin lymphoma (cHL) (Fig. 1 Mixed cellularity classical Hodgkin lymphoma treated with frontline brentuximab vedotin, and subsequent development of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma, polymorphic type. Cervical lymph node biopsy showed Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL), polymorphic pattern [[4]], non-germinal centre B-cell (non-GCB, Hans algorithm) in origin immunohistochemically (Fig. [Extracted from the article]

Inflammatory bowel disease (IBD) is a life-threatening and chronic inflammatory disease of gastrointestinal tissue, with complex pathogenesis. Current research on IBD has mainly focused on bacteria; however, the role of fungi in IBD is largely unknown due to the incomplete annotation of fungi in current genomic databases. With the development of molecular techniques, the gut mycobiome has been found to have great diversity. In addition, increasing evidence has shown intestinal mycobiome plays an important role in the physiological and pathological processes of IBD. In this review, we will systemically introduce the recent knowledge about multi-dimensional fungal dysbiosis associated with IBD, the interactions between fungus and bacteria, the role of fungi in inflammation in IBD, and highlight recent advances in the potential therapeutic role of fungus in IBD, which may hold the keys to develop new predictive, therapeutic or prognostic approaches in IBD. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. Methods. First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results. JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. Conclusions. The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ. [ABSTRACT FROM AUTHOR]

Background: The relation between the ATP-binding cassette subfamily B member 1 (ABCB1) gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 (G2677T) and rs1128503 (C1236T) single-nucleotide polymorphisms (SNPs) of ABCB1 but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population. Methods: The study population included 292 patients with MDD. All patients were assessed at baseline and at first, second, fourth, and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAM-D17) to determine their therapeutic responses to SSRIs and SNRIs. Results: In the SSRI therapy group, the genotype or allele distribution of six SNPs was not significantly different between responders and nonresponders. In the SNRI therapy group, only rs2032583 was associated with a therapeutic response to SNRIs. The C allele of the ABCB1 rs2032583 polymorphism was negatively correlated with therapeutic responses according to logistic regression analysis. Conclusion: The ABCB1 gene polymorphisms may not be associated with therapeutic responses to SSRIs but not with SNRIs. The TT genotype of rs2032583 could be a predictive factor of improved treatment responses to SNRIs in the Chinese population. These findings should be replicated in future studies with larger patient groups. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: There are several popular treatment options currently available for stereotactic radiosurgery (SRS) of multiple brain metastases: 60Co sources and cone collimators around a spherical geometry (GammaKnife), multi-aperture dynamic conformal arcs on a linac (BrainLab Elements™ v1.5), and volumetric arc therapy on a linac (VMAT) calculated with either the conventional optimizer or with the Varian HyperArc™ solution. This study aimed to dosimetrically compare and evaluate the differences among these treatment options in terms of dose conformity to the tumor as well as dose sparing to the surrounding normal tissues. Methods and Materials: Sixteen patients and a total of 112 metastases were analyzed. Five plans were generated per patient: GammaKnife, Elements, HyperArc-VMAT, and two Manual-VMAT plans to evaluate different treatment planning styles. Manual-VMAT plans were generated by different institutions according to their own clinical planning standards. The following dosimetric parameters were extracted: RTOG and Paddick conformity indices, gradient index, total volume of brain receiving 12Gy, 6Gy, and 3Gy, and maximum doses to surrounding organs. The Wilcoxon signed rank test was applied to evaluate statistically significant differences (p < 0.05). Results: For targets ≤ 1 cm, GammaKnife, HyperArc-VMAT and both Manual-VMAT plans achieved comparable conformity indices, all superior to Elements. However, GammaKnife resulted in the lowest gradient indices at these target sizes. HyperArc-VMAT performed similarly to GammaKnife for V12Gy parameters. For targets ≥ 1 cm, HyperArc-VMAT and Manual-VMAT plans resulted in superior conformity vs. GammaKnife and Elements. All SRS plans achieved clinically acceptable organs-at-risk dose constraints. Beam-on times were significantly longer for GammaKnife. Manual-VMATA and Elements resulted in shorter delivery times relative to Manual-VMATB and HyperArc-VMAT. Conclusion: The study revealed that Manual-VMAT and HyperArc-VMAT are capable of achieving similar low dose brain spillage and conformity as GammaKnife, while significantly minimizing beam-on time. For targets smaller than 1 cm in diameter, GammaKnife still resulted in superior gradient indices. The quality of the two sets of Manual-VMAT plans varied greatly based on planner and optimization constraint settings, whereas HyperArc-VMAT performed dosimetrically superior to the two Manual-VMAT plans. [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients.Methods: We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review.Results: After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD - 65.82 [- 194.19, 62.55]), lactate (MD 0.49 [- 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [- 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD - 0.04 [- 0.13, 0.05]), serum lactate level (MD 0.69 [- 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [- 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h.Conclusions: Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure. [ABSTRACT FROM AUTHOR]

Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia. The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1. DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway. [Display omitted] • This study examined the effects of Dingxin Recipe Ⅲ in hyperlipidemia based on gut barrier and lipid metabolism. • Mechanisms of Dingxin Recipe Ⅲ were explored by fecal microbiota transplantation and short chain fatty acid intervention. • Dingxin Recipe Ⅲ improved HFD-induced hyperlipidemia and gut barrier, including physical barrier, gut microbiota, and SCFAs. • Dingxin Recipe Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway. [ABSTRACT FROM AUTHOR]

Sulbactam is an atypical β-lactam medication and reported to be neuroprotective by up-regulating glial glutamate transporter-1 (GLT-1) in rats. The present study was undertaken to study the role of p38 MAPK signal pathway in sulbactam induced up-regulation of GLT-1 expression in astrocytes and anti-ischemic effect. Neuron-astrocyte co-cultures and astrocyte cultures from neonatal Wistar rats were used. Cerebral ischemia was mimicked by oxygen-glucose deprivation (OGD). Hoechst (HO)/propidium iodide (PI) double fluorescence staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay were used to evaluate neuronal death and cell viability, respectively. Immunocytochemistry and Western blot were used to detect protein expressions. Sulbactam pre-incubation significantly and dose-dependently prevented neuronal death and decline in cell viability induced by OGD in neuron-astrocyte co-cultures, and upregulated GLT-1 expression in astrocyte cultures endured OGD, which suggested that sulbactam might protect neurons against OGD by up-regulating astrocytic GLT-1 expression. It was further shown that the phosphorylated-p38 MAPK expression in astrocytes was up-regulated after the sulbactam pre-incubation and this up-regulation was moderate in amplitude. Especially, the time course of the up-regulation of phosphorylated-p38 MAPK was obviously earlier than that of GLT-1, which suggested possibility that p38 MAPK might be an upstream signal for GLT-1 up-regulation induced by sulbactam. We further found that SB203580, the specific inhibitor of p38 MAPK, dose-dependently inhibited the GLT-1 up-regulation induced by sulbactam either in non- or OGD-treated astrocytes and the protective effect of sulbactam on co-cultured neurons against OGD. Taken together, it might be concluded that sulbactam protects cerebral neurons against OGD by up-regulating astrocytic GLT-1 expression via p38 MAPK signal pathway. [ABSTRACT FROM AUTHOR]

Aim of the Study: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. Materials and Methods: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation. For in vivo silencing of PDE1A in rat lung, a nonspecific control siRNA or PDE1A-specific siRNA was used to treat rat through nasal instillation. Human normal pulmonary fibroblasts MRC-5 and hFL1 and rat lung fibroblasts were used as in vitro model. Immunohistochemistry and immunoflurescence staining were performed to detect PDE1A and α-SMA expression. Reverse transcription-qPCR was performed to detect microRNA and mRNA expression. In vitro wound healing assay was performed to detect pulmonary fibroblasts'mortality ability. Results: In vitro studies showed that PDE1A can stimulate lung fibroblasts to undergo myofibroblastic changes. This led to the identification of miR-541-5p as one of the miRNA candidates associated with bleomycin response. We found that miR-541-5p expression is downregulated in TGF-β-treated lung fibroblasts and the rat pulmonary fibrosis model. Overexpression of miR-541-5p in lung fibroblasts inhibited mortality of human lung fibroblasts. Conclusions: MiR-541-5p is a key effector in lung fibroblastsby by regulating PDE1A expression at protein translation level and its overexpression is protective against bleomycin-induced lung fibrosis. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue that possesses anti-inflammatory effects. GLP-1 receptor (GLP-1R) agonists have been demonstrated to serve a pivotal role in the treatment of obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). However, the specific function and underlying mechanisms of GLP-1R in COPD remain uncertain. The aim of the present study was to investigate the action and underlying mechanisms of GLP-1R in airway smooth muscle (ASM) cells from COPD patients. GLP-1R expression levels were markedly decreased in ASM cells from COPD patients compared with those from healthy controls. ASM cell proliferation and migration, and the levels of the inflammatory cytokines interleukin (IL)-1β, IL-4, tumor necrosis factor (TNF)-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured. Transfection of pcDNA3.1-GLP-1R had inhibitory effects on ASM cell proliferation and migration, whereas GLP-1R small interfering (si)RNA reversed these effects. Furthermore, the present study demonstrated that GLP-1R overexpression markedly suppressed IL-1β, IL-4, TNF-α and GM-CSF levels. GLP-1R overexpression upregulated the expression levels of adenosine triphosphate-binding cassette, subfamily A, member 1 (ABCA1) in ASM cells, and the effects of GLP-1R on cell proliferation and migration, and inflammatory cytokine expression in ASM cells was abolished by siRNA-mediated silencing of ABCA1. The results of the present study suggested that GLP-1R contributes to COPD pathology, potentially via an ABCA1-mediated pathway. [ABSTRACT FROM AUTHOR]

Aim:The current treatments of toxic epidermal necrolysis (TEN) are limited to the discontinuation of a suspect medication and supportive measures. We conducted a retrospective study to evaluate the efficacy of adding continuous venovenous hemofiltration (CVVH) and hemoperfusion (HP) to the conventional treatment for TEN. Methods:TEN patients who were admitted to our center between January 2008 and May 2016 were considered as candidates. The included patients were divided into the CVVH&HP group (n = 34) and the conventional group (n = 34) according to their accepted therapies during hospital stay. Results:The patients in the conventional group had a significantly reduced 28-day survival proportion compared with patients in the CVVH&HP group (73.5 versus 91.2%,p = .047). The adjusted results demonstrated that the conventional group had a significantly higher risk of 28-day mortality as well. Moreover, patients in the CVVH&HP group were associated with significantly shorter hospital stay, rash, fever, and antibiotic durations. However, the addition of CVVH&HP to conventional treatment did not significantly increase the in-hospital cost. Conclusions:In conclusion, CVVH&HP might be a safe and effective adjuvant therapy for TEN. Further well-designed studies are warranted to obtain robust evidence. [ABSTRACT FROM PUBLISHER]

Nuclear factor E2-related factor 2 (Nrf2) is considered a promising target against diabetic complications such as cardiovascular diseases and diabetic nephropathy. Herein, we investigated the effects of a potential Nrf2 modulator, salvianolic acid A (SAA), which is a natural polyphenol, on diabetes-associated macrovascular and renal injuries in streptozotocin-induced diabetic mice. Given that lowering glucose is the first objective of diabetic patients, we also examined the effects ofSAAcombined with metformin (MET) on both complications. Our results showed that SAA significantly increased the macrovascular relaxation response to acetylcholine and sodium nitroprusside in diabetic mice. Interestingly, treatment with SAA alone only provided minor protection against renal injury, as reflected by minor improvements in impaired renal function and structure, despite significantly reduced oxidative stress observed in the diabetic kidney. We demonstrated that decreased oxidative stress and NF-κB p65 expression were associated with SAA-induced expression of Nrf2-responsive antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (quinone) 1 (NQO-1), and glutathione peroxidase-1 (GPx-1) in vivo or in vitro, which suggested thatSAAwas a potential Nrf2 modulator. More significantly, compared with treatment with eitherSAAor MET alone, we found that their combination provided further protection against the macrovascular and renal injury, which was at least partly due to therapeutic activation of both METmediated AMP-activated protein kinase and SAA-mediated Nrf2/antioxidant-response element pathways. These findings suggested that polyphenol Nrf2 modulators, especially combined with drugs activating AMP-activated protein kinase, including hypoglycemic drugs, are worthy of further investigation to combat diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Gait-related symptoms are often refractory to current available treatment options with a significant reduction in quality of life in Parkinson's disease.Objectives: The objective of this study was to determine the long-term efficacy and safety of unilateral pedunculopontine area stimulation for refractory gait and balance impairment in Parkinson's disease.Methods: This study used periodic randomized double-blinded assessments until 4 years postoperatively. The primary outcomes were gait-related items of the UPDRS part II and the MDS-UPDRS part III.Results: At baseline, the median age and disease duration was 63 years (interquartile range: 62, 65) and 15 years (interquartile range: 11, 20). At 2 years, patient-reported freezing (UPDRS part II, off-time) was significantly better when compared with baseline (P =.028), with 62.5% of responders. At 4 years, there was no significant change in the used outcomes, but 66.7 % (n = 4 of 6) were responders for off-time patient-reported freezing and falling.Conclusions: Pedunculopontine area stimulation has an initial but not sustained benefit for gait-related symptoms. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (PTB) has been recognized as a crucial long term risk factor for multiple non-communicable diseases. However, studies between the relationship of PTB and the risk of acute childhood leukemia have yielded inconclusive results. Therefore, we performed a meta-analysis to systematically review the current literature to investigate whether PTB is associated with increased risk of acute childhood leukemia. Methods: Three electronic databases (PubMed, Web of Science, and EMBASE) were searched up to December 1st, 2015. Relevant studies reporting the association between PTB and subsequent risk of acute childhood leukemia were included for further evaluation. Statistical analysis was performed using Revmen 5.3 and Stata 10.0. Results: A total of 12 studies for acute childhood leukemia, eight studies for acute lymphoblastic leukemia (ALL), and seven studies for acute myeloid leukemia (AML) were included in the current meta-analyses. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate the relationship between PTB and acute childhood leukemia as well as its two subtypes: ALL and AML. Our results suggested that PTB was significantly associated with increased risk of acute childhood leukemia (OR = 1.09, 95% CI = 1.02-1.17, P = 0.01) and AML (OR = 1.42, 95% CI = 1.21-1.67, P < 0.01). However, PTB was not significantly associated with an increased risk of ALL (OR = 1.04, 95% CI = 0.96-1.13, P = 0.29). Conclusion: Our data showed that PTB increased the risk of AML. Further studies are required to explore causality and dissect the biological mechanisms involved. [ABSTRACT FROM AUTHOR]

Previous studies have identified the beneficial effects of electroacupuncture (EA) on motor behaviors in Parkinson’s disease (PD). However, the role and potential mechanisms of EA in PD-associated depression remain unclear. In the present study, a rat model of PD with unilateral 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle was treated using EA for 4 weeks. We found that 100 Hz EA improved several motor phenotypes. In addition, tyrosine hydroxylase (TH) immunohistochemical analysis showed that EA had a minimal impact on the TH-positive profiles of the ipsilateral ventral tegmental area. Compared with the 6-OHDA group, long-term EA stimulation significantly increased sucrose solution consumption and decreased immobility time in the forced swim test. EA treatment did not alter dopamine, norepinephrine, and serotonin levels in the striatum and hippocampus. Noticeably, EA treatment reversed the 6-OHDA-induced abnormal expression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in the midbrain and hippocampus. These results demonstrate that EA at 100-Hz possesses the ability to improve depressive-like symptoms in PD rats, which is, at least in part, due to the distinct effect of EA on the mesostriatal and mesocorticolimbic dopaminergic pathways. Moreover, BDNF seems to participate in the effect of EA in PD. [ABSTRACT FROM AUTHOR]

The immunofluorescence pattern in adnexal structures may be of value, especially when the epidermis is not well represented in diagnostic sections. We studied a total of 88 cases of pemphigus vulgaris ( PV) and bullous pemphigoid ( BP) accessioned between 2010 and 2015 (40 cases of PV and 48 cases of BP). Immunofluorescence patterns and sensitivity in adnexal structures were similar to those observed in the epidermis. One case of PV and three cases of BP showed weak or absent fluorescence in the epidermis, while the eccrine glands were strongly positive, suggesting that careful examination of adnexal structures can be of value. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the effect and safety of citrate versus heparin anticoagulation for continuous renal replacement therapy (CRRT) in critically ill patients by performing a meta-analysis of updated evidence.Methods: Medline, Embase, and Cochrane databases were searched for eligible studies, and manual searches were also performed to identify additional trials. Randomized controlled trials (RCTs) assessing the effect of citrate versus heparin anticoagulation for CRRT were considered eligible for inclusion.Results: Eleven RCTs with 992 patients and 1998 circuits met the inclusion criteria. Heparin was regionally delivered in two trials and systemically delivered in nine trials. Citrate for CRRT significantly reduced the risk of circuit loss compared to regional (HR 0.52, 95 % CI 0.35–0.77, P = 0.001) and systemic (HR 0.76, 95 % CI 0.59–0.98, P = 0.04) heparin. Citrate also reduced the incidence of filter failure (RR 0.70, 95 % CI 0.50–0.98, P = 0.04). The citrate group had a significantly lower bleeding risk than the systemic heparin group (RR 0.36, 95 % CI 0.21–0.60, P < 0.001) and a similar bleeding risk to the regional heparin group (RR 0.34, 95 % CI 0.01–8.24, P = 0.51). The incidences of heparin-induced thrombocytopenia (HIT) and hypocalcemia were increased in the heparin and citrate groups, respectively. No significant survival difference was observed between the groups.Conclusions: Given the lower risk of circuit loss, filter failure, bleeding, and HIT, regional citrate should be considered a better anticoagulation method than heparin for CRRT in critically ill patients without any contraindication. [ABSTRACT FROM AUTHOR]

Following extensive surgical debridement in the treatment of infection, a “dead space” can result following surgical closure that can fill with hematoma, an environment conducive to bacterial growth. The eradication of dead space is essential in order to prevent recurrent infection. This study describes a novel small animal model to investigate dead-space management in muscle tissue. Two absorbable test materials were implanted in each animal; beads of calcium sulfate alone, and beads loaded with vancomycin and tobramycin. In-life blood samples and radiographs were taken from each animal following implantation. Animals were sacrificed at 1, 7, 21, 42, and 63 days post-operatively (n = 4), and implant sites were analysed by micro-computed tomography, histology and immunohistochemistry. Complete resorption was confirmed radiographically at 3 weeks post-implantation. Histologically, the host tissue response to both materials was identical, and subsequent healing at the implant sites was observed with no dead space remaining. Vancomycin was not detected in blood serum. However, peak tobramycin levels were detected in all animals at 6 hours post-implantation with no detectable levels in any animals at 72 hours post implantation. Serological inflammatory cytokine expression for IL-6, TNF-α and IL-1β indicated no unusual inflammatory response to the implanted materials or surgical procedure. The model was found to be convenient and effective for the assessment of implant materials for management of dead space in muscle tissue. The two materials tested were effective in resolving the surgically created dead space, and did not elicit any unexpected adverse host response. [ABSTRACT FROM AUTHOR]

Background: Malignant peritoneal mesothelioma (MPM) is an uncommon disease with a dismal prognosis and unclear natural history. The present study aims to assess potential prognostic factors and management of MPM. Methods: Clinical records of 39 patients with MPM between December 2003 and April 2014 were retrospectively reviewed. Overall survival was identified with Kaplan-Meier curves and Cox regression analysis. Results: Mean age of 39 patients was 55.0 years; asbestos exposure was recorded in two patients. Main presentations were abdominal distension, abdominal pain, and weight loss. Thrombocytosis, low serum albumin level, and anemia were principal laboratory abnormalities. Ascites, peritoneal cavity mass, and peritoneum thickening were the main signs on CT scans. Cytoreductive surgery (CRS) plus adjuvant therapies were performed in 22 patients, single chemotherapy in 13, and best supportive care in 4. Median survival time was 10.0 months after pathological diagnosis, with a 6-, 12-, 18-, and 24-month survival rate of 84.4, 31.6, 18.5, and 15.8 %, respectively. Significant prognostic factors were age, performance status (PS), abdominal pain, serum albumin level, thrombocytosis, and treatment strategy on univariate analysis, while only age, abdominal pain, and treatment strategy hold statistical significance on multivariate analysis. Conclusions: Age ≤65 years, abdominal pain, and CRS plus adjuvant therapy are independent positive prognostic factors of MPM. [ABSTRACT FROM AUTHOR]

Ceftriaxone(Cef) selectively increases the expression of glial glutamate transporter-1 ( GLT-1), which was thought to be neuroprotective in some circumstances. However, the effect of Cef on glutamate uptake of GLT-1 was mostly assayed using in vitro studies such as primary neuron/astrocyte cultures or brain slices. In addition, the effect of Cef on neurons in different ischemic models was still discrepant. Therefore, this study was undertaken to observe the effect of Cef on neurons in global brain ischemia in rats, and especially to provide direct evidence of the up-regulation of GLT-1 uptake for glutamate contributing to the neuronal protection of Cef against brain ischemia. Neuropathological evaluation indicated that administration of Cef, especially pre-treatment protocols, significantly prevented delayed neuronal death in hippocampal CA1 subregion normally induced by global brain ischemia. Simultaneously, pre-administration of Cef significantly up-regulated the expression of GLT-1. Particularly, GLT-1 uptake assay with 3H-glutamate in living cells from adult rats showed that up-regulation in glutamate uptake accompanied up-regulated GLT-1 expression. Inhibition of GLT-1 by antisense oligodeoxynucleotides or dihydrokainate significantly inhibited the Cef-induced up-regulation in GLT-1 uptake and the neuroprotective effect against global ischemia. Thus, we may conclude that Cef protects neurons against global brain ischemia via up-regulation of the expression and glutamate uptake of GLT-1. [ABSTRACT FROM AUTHOR]

The healing of critical sized segmental defects is an ongoing clinical problem. No method has achieved pre-eminence. The Masquelet technique is a relatively new innovation involving the induction of a fibrous tissue membrane around the bone defect site taking advantage of the body’s foreign body reaction to the presence of a polymethylmethacrylate (PMMA) spacer. The aim of this study was to investigate the properties and characteristics of this induced membrane and its effectiveness when used in conjunction with allograft or an allograft/autograft mix as filler materials in an ovine critical sized defect model. The resultant induced membrane was found to be effective in containing the graft materials in situ. It was demonstrated to be an organised pseudosynovial membrane which expressed bone morphogenic protein 2 (BMP2), transforming growth factor- beta (TGFβ), vascular endothelial growth factor (VEGF), von Willerbrand factor (vWF), interleukin 6 (IL-6) and interleukin 8 (IL-8). While more new bone growth was evident in the test groups compared to the controls animals at 12 weeks, the volumes were not statistically different and no defects were fully bridged. Of the two graft material groups, the allograft/autograft mix was shown to have a more rapid graft resorption rate than the allograft only group. While the Masquelet technique proved effective in producing a membrane to enclose graft materials, its ability to assist in the healing of critical sized segmental defects when compared to empty controls remained inconclusive. [ABSTRACT FROM AUTHOR]

Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P=0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule- associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) leads to several neurologic damages to patients with sensory and motor function loss. Although some inspiring results were reported in animal, even in non-human primate models, the clinical translation of these research achievements barely move forward for the SCI patients. This review mainly focused on the pathogenesis of the primary and secondary injury, the clinical therapies and the new technologies in spinal cord injury. Moreover, the key scientific issues on this field were discussed in the review. Finally, some suggestions were proposed for the scientific and clinical researches. [ABSTRACT FROM AUTHOR]

Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone– independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALKinduced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to examine the angiographic result and its outcome predictors using the combination of paclitaxel-eluting balloon (PEB) and Genous stent. Background This approach to treat coronary stenoses is a logical strategy to strike a balance between minimizing restenosis and stent thrombosis. Methods From November 2010 to June 2012, 40 symptomatic patients with 44 de novo coronary lesions of diameter stenosis ≥50% were treated with the combination of PEB and Genous stents. Angiographic and clinical follow-up were intended at 6 and 9 months, respectively. Results The mean age of patients was 61 ± 11 years, with male predominance (83%). Diabetes mellitus and end-stage renal failure on peritoneal dialysis were found in 15 (38%) and 10 (25%) patients, respectively. Patients received dual antiplatelet therapy for 5.1 ± 1.5 months post procedure. The size and length of PEB used was larger than the stents (3.13 ± 0.46 mm and 28 ± 9 mm vs. 2.98 ± 0.36 mm and 23 ± 7 mm). Restudy angiography was performed on 41 (95%) lesions in 37 (93%) patients at 5.9 ± 1.7 months. Angiographic restenosis was seen in 5 (12%) lesions, and significantly associated with diabetes mellitus and dialysis dependency; the late lumen loss was 0.38 ± 0.37 mm. At 9-month follow-up, no stent thrombosis was observed. Conclusions The use of PEB combined with Genous stent is associated with a reasonably low restenosis and late lumen loss, whereas diabetes mellitus and renal failure with dialysis are poor predictors of angiographic restenosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the odontogenic potential of bone marrow mesenchymal stem cells (BMMSCs) to differentiate into odontoblast-like cells under the morphogenetic influence of dentine matrix as a possible basis for new stem cell-mediated therapeutic approaches to pulp diseases. Design: BMMSCs were harvested from the whole bone marrow and cells at passages 3–5 were used for subsequent experiments. For in vitro studies, 1×104 cells were seeded on the surface of dentine slabs and co-cultured for 2 weeks in 24-well plates, then fixed, decalcified, embedded in paraffin and serial sections were processed for analyses. Haematoxylin-eosin (HE) staining was used for the morphological analysis of BMMSCs on the dentine slabs. The protein expression of dentine sialoprotein (DSP) in co-cultured BMMSCs was detected by immunohistochemical (IHC) staining. For in vivo studies, 5×106 cells were collected as cell pellets, seeded onto dentine slices and transplanted into renal capsules for 6 weeks. Histological analyses of harvested tissues were performed as described for the in vitro studies. Total RNA and protein were extracted from harvested tissues and Dspp/DSP expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. Results: After 2 weeks of co-culture with dentine slabs, BMMSCs demonstrated good viability in terms of morphological appearance and some showed polarization and extension of their cytoplasmic processes into dentine tubules with DSP expression. In vivo study demonstrated similar morphological changes and DSP expression in cells adjacent to dentine. RT-PCR and Western blot also demonstrated that the expression of Dspp/DSP in the co-cultured BMMSCs groups was higher than in the control groups. Conclusion: Dentine matrix can signal morphogenic induction of differentiation of BMMSCs into odontoblast-like cells in vivo and in vitro. [Copyright &y& Elsevier]

Abstract: Purpose: Quercetin (3, 3,′ 4′, 5, 7 – five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies. Methods and materials: The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy. Results: We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins. Conclusion: We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation. [Copyright &y& Elsevier]

Abstract: Bone morphogenetic proteins (BMPs) are potent bone inducers used clinically to enhance fracture repair. BMPs have been shown to be produced in the fracture callus; however, the comparative expression of BMPs and BMP signaling components has only been partially examined at the cellular level. The aim of the present study was to establish a detailed spatiotemporal localization of BMPs and BMP signaling components in mouse models of stabilized and nonstabilized fractures. During healing of nonstabilized fractures, which occurs via endochondral ossification, BMP2, 3, 4, 5, and 8, noggin, BMPRIA, BMPRII, and pSmad 1/5/8 were immunolocalized in the activated periosteum as early as 3 days after fracture. BMP2, 4, 5, 6, 7, and 8 and noggin were also found in isolated inflammatory cells within granulation tissue during the early stages of repair, but not BMP receptors and effectors. During the soft callus phase of repair, all BMPs and BMP signaling components were detected in chondrocytes with various intensities of staining depending on the stage of chondrocyte differentiation and their location in the callus. The strongest staining was observed in hypertrophic chondrocytes with decreased intensity during the hard callus phase of repair. All BMPs and components of the BMP pathway were detected in osteoblasts and osteocytes within new bone, with strongest intensity of immunoreaction reported during the early soft callus phase followed by decreasing intensity during the hard callus phase of repair. Most components of the BMP pathway were also detected in endothelial cells associated with new bone. In stabilized fractures that heal strictly via intramembranous ossification, BMPs and BMP antagonists were detected in isolated inflammatory cells and BMP signaling components were not detectable in osteoblasts or osteocytes within new bone. In conclusion, the BMP signaling pathway is primarily activated during fracture healing via endochondral ossification, suggesting that this pathway may influence the mode of healing during the recruitment of skeletal progenitors. [Copyright &y& Elsevier]

Objective: To explore the key targets and mechanisms of action of Mume Fructus in the treatment of colorectal cancer based on network pharmacology. Methods: TCMSP database was adopted to screen the active components and potential targets of Mume Fructus. GeneCards and Disgest databases were used to collect disease targets for colorectal cancer. Cytoscape software was used to construct the component-target network diagram. STRING database was used to draw the PPI network. Finally, DAVID database was used to perform GO biological process analysis and KEGG pathway enrichment analysis of centre target proteins. Results: There were 58 potential targets for the treatment of colorectal cancer in Mume Fructus. The protein interaction network suggested that TP53、AKT1、MAPK8、JUN、 EGF and TNF may be the core targets for the treatment of colorectal cancer in Mume Fructus. Gene ontology enrichment analysis showed 108 cellular biological processes, and KEGG pathway enrichment analysis showed 88 related signaling pathways, including p53, TNF, HIF-1 and so on. Conclusion: The treatment of colorectal cancer by Mume Fructus may be multi-target, multi-channel, and multi-level. This consequence may provide ideas and a basis for further research. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the use of veno-venous hemofiltration with gradient sodium fluid for treatment of acute hypernatremia in badly burned patients. It elaborates various health-related factors of severely burned patients including secondary sepsis, mechanical ventilation and solute dieresis. It notes that the study examines nine patients with acute hypernatremia and treated at an intensive care unit.

The article presents a case study of a 68-year-old man who was presented with cervical lymphadenopathy, bilateral tonsillar enlargement and ulcerations. It mentions that bone marrow examination reveals acute myeloid leukemia (AML) and pathological features were consistent with Langerhans cell histiocytosis (LCH). It discusses the use of vinblastine, etoposide and cyclophosphamide for the treatment.

Sulfa antibiotics (SAs) and quorum-sensing inhibitor (QSI) may pose potential ecological risks because mixed using of them has been proposed to inhibit bacteria from generating antibiotic resistance. This study investigated the time-dependent hormesis of single and binary mixtures of QSI and SAs of Vibrio fischeri ( V. fischeri ) for 0–24 h. Although the low-dose SAs stimulated the expression of LuxR protein, the high-dose SAs could inhibit bacteria growth by competitively binding to dihydropteroate synthase. Moreover, AinR protein was bound to Benzofuran-3(2H)-one (B3O) with low concentration, thus the N-octanoyl homoserine lactone signal molecules (C8) has chance to bind to LuxR protein to promote light emission. The hormesis effect induced by the mixtures could be deduced that SAs promoted the expression of LuxR protein and B3O increases the chance of C8 binding to LuxR. Our findings facilitate new insight into the mechanistic study of hormesis and ecological risks of the chemical mixtures. [ABSTRACT FROM AUTHOR]

Background Both misoprostol and prostaglandin E2 (PGE2) gel are used for labor induction in women with premature rupture of membranes (PROM). Objectives To evaluate studies comparing the effects of misoprostol and PGE2 gel in labor induction. Search strategy Databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant papers. Selection criteria Randomized controlled trials comparing the use of misoprostol and PGE2 gel for labor induction in women with PROM were included. Data collection and analysis For meta-analyses, the Mantel–Haenszel method was used for dichotomous data, and the inverse variance method was used for continuous data. Main results Four randomized controlled studies (n = 615) were included. There were no significant differences between the two groups in the induction-to-delivery interval (mean difference – 4.44 hours; 95% confidence interval [CI] –9.35 to 0.48), rate of cesarean delivery (odds ratio [OR] 0.90; 95% CI 0.44–1.85), and rate of neonatal intensive care unit admission (OR 0.89; 95% CI 0.57–1.38). Women receiving misoprostol had a significantly higher rate of tachysystole than did those receiving PGE2 gel (OR 4.84; 95% CI 2.46–9.54). Conclusions Misoprostol is as efficacious and safe as PGE2 gel for labor induction in women with PROM. [ABSTRACT FROM AUTHOR]

Steerable needles can potentially improve the effectiveness of diagnostic and therapeutic procedures, such as biopsy and cancer treatment, by increasing the targeting accuracy and reaching previously inaccessible targets. A discrete potential field algorithm based on three dimensional (3D) anatomical structures is proposed in this paper to plan the needle path in minimally invasive surgery. A 3D kinematic model of needle steering is formulated using Lie group theory. Model parameters are fitted using experimental data acquired via a 2-degree of freedom robotic device and an ultrasound imaging device. To execute the paths with variable curvatures, the model is incorporated with duty cycled spinning. Empirical formula between needle curvature and duty cycled factor is obtained through insertion experiments. To improve the targeting accuracy, a path tracking algorithm is developed by correcting for the heading error and cross-track error of the needle tip. The targeting error of the simulation is 0.29 mm. We experimentally evaluate the path tracking model and it achieves an average targeting error of 1.15 ± 0.56 mm in 3D environments with anatomical obstacles. The results of simulation are in agreement with steering experiments, showing that the discrete potential field algorithm and path tracking model have the potential to improve targeting accuracy and advance the therapeutic and diagnostic procedures. [ABSTRACT FROM AUTHOR]

Background and Objectives: The present study was conducted to evaluate the effect of cod skin peptide (CSPE) on chemotherapy-induced toxicity in gastric cancer patients.Methods and Study Design: A cohort of 60 gastric cancer patients for chemotherapy was randomly divided into two groups (n=30 per group), who were orally treated with either supplemental CSPE or placebo apart from chemotherapy. The hematologic and gastrointestinal toxicities experienced by the patients, as well as their Karnofsky Performance Status (KPS) as an index of quality of life was evaluated.Results: Leukocyte counts and haemoglobin levels were significantly reduced in the group treated with peptide (p<0.05), while gastrointestinal toxicity was not affected (p>0.05). KPS consists of 11 categories of quality of life, and the score denoted in deciles ranges from 100 (asymptomatic, normal function) to 0 (death). The KPS score is used to evaluate a cancer patient's ability to function at work and home, the severity of symptoms, and the patient's need for personal and medical care. Treatment with CSPE significantly improved the quality of life of patients, as indicated by increased KPS scores (p<0.05).Conclusions: CSPE can potentially be considered as a food supplement that can be used to improve the quality of life of cancer patients. [ABSTRACT FROM AUTHOR]

Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5 mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro . Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro . Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats. [ABSTRACT FROM AUTHOR]

Background The hybrid decompression technique (corpectomy combined with discectomy) and anterior cervical corpectomy with fusion (ACCF) both provide good neurological recovery and disease stabilization for the treatment of multilevel cervical spondylotic myelopathy (CSM). However, no single study has been large enough to determine definitively which one is superior for this condition. Objective A meta-analysis was conducted to compare the clinical efficacy and safety of the hybrid decompression technique versus ACCF for the treatment of multilevel CSM. Methods Electronic databases such as PubMed, MEDLINE, EMBASE, Google Scholar, and the Cochrane Library were selected to search for potentially relevant trials up to April 2015 that compared the outcomes of the hybrid technique with ACCF for the treatment of multilevel CSM. Data extraction and quality assessment were performed according to Cochrane Collaboration guidelines. The outcome assessments were duration of surgery, blood loss, Cobb angle of C2-C7, segment angle, fusion rate, Japanese Orthopedics Association score, Neck Disability Index, and complications. The results were expressed as the odds ratio (OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with a 95% confidence interval (CI). Results Five controlled clinical trials published between 2009 and 2013, involving 356 patients (hybrid, 196; ACCF, 160) with 3- or 4-level CSM were retrieved in this study. Overall, there were significant differences between the 2 treatment groups for blood loss (MD = −38.69, 95% CI = −54.62 to −22.76, P < 0.01), fusion rate (OR = 2.56, 95% CI = 1.11 to 5.93, P = 0.03), and complications (OR = 0.25, 95% CI = 0.15 to 0.43, P < 0.01). However, no significant differences were found for duration of surgery (MD = −4.50, 95% CI = −22.902 to 13.91, P = 0.63), Cobb angle of C2-C7 after surgery (MD = 3.32, 95% CI = −3.72 to 10.37, P = 0.35), segment angle after surgery (MD = 2.87, 95% CI = −2.47 to 8.21, P = 0.29), Japanese Orthopedics Association score (MD = −0.07, 95% CI = −0.36 to 0.22, P = 0.62), or Neck Disability Index (MD = −0.86, 95% CI = −3.26 to 1.54, P = 0.48). Conclusion Based on this meta-analysis, both the hybrid technique and ACCF can achieve good results for CSM. However, the hybrid technique is associated with significantly less blood loss, complications, and a higher fusion rate than ACCF. [ABSTRACT FROM AUTHOR]

In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l- p -tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C 18 column (100 × 2.1 mm, 3.5 μm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150 × 2.1 mm, 3 μm) using acetonitrile and water (containing 5 mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs ( m/z ) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable. [ABSTRACT FROM AUTHOR]

Background context The ideal tissue-engineered solution for any bone graft substitute is to assist in the rapid formation of bone and facilitate fusion. Purpose The present study aims to evaluate this E-BMP-2 (Escherichia coli-derived human bone morphogenetic protein-2) in ovine posterolateral lumbar fusion (PLF) to examine the influence of dose and overall performance in a model with similar graft size and diffusive challenges to the human. Study design/setting In vivo large animal model study. Methods An adult ovine PLF was performed in 30 animals with groups of E-BMP-2 with a beta-tricalcium phosphate (β-TCP) carrier at three different dosages, β-TCP alone, and autograft from the iliac crest. The fusions were assessed by radiography (X-ray and microcomputed tomography), mechanical testing, and hard-tissue histology with bone labels at 6, 8, and 10 weeks along with routine paraffin histology at 12 weeks. Results Results showed increasing new bone and fusion rate with E-BMP-2 dose, whereas β-TCP alone was largely resorbed and did not achieve fusion in this model at 12 weeks. Autograft showed similar grading for the amount of bone between the transverse processes but a lower fusion rate than β-TCP/E-BMP-2 groups. Bone labels revealed new bone formation at all time points for the E-BMP2 groups, whereas the autograft group showed active bone formation at 10 weeks. Beta-tricalcium phosphate displayed reliable incorporation into the decorticated host bone, whereas limited new bone was found between the transverse processes. At the center of the fusion mass, increased E-BMP-2 dose led to increased incorporation of β-TCP by new bone. Conclusions These results suggest that E-BMP-2 was capable of producing posterolateral fusion in the ovine model that is equal to or superior to autologous graft in terms of fusion rate and mechanical strength. E-BMP-2 dose had considerable influence on β-TCP granule resorption. [ABSTRACT FROM AUTHOR]