Population pharmacokinetics of tigecycline in critically ill patients with severe infections

We sought to describe the population pharmacokinetics of tigecycline in critically ill patients and to determine optimized dosing regimens of tigecycline for different bacterial infections. This prospective study included 10 critically ill patients given a standard dose of tigecycline. Blood samples were collected during one dosing interval and were analyzed using validated chromatography. Population pharmacokinetics and Monte Carlo dosing simulations were undertaken using Pmetrics. Three target exposures, expressed as ratios of the 24-h area under the curve to MICs (AUC(0-24)/MIC), were evaluated (>= 17.9 for skin infections, >= 6.96 for intraabdominal infections, >= 4.5 for hospital-acquired pneumonia). The median age, total body weight, and body mass index (BMI) were 67 years, 69.1 kg, and 24.7 kg/m(2), respectively. A two-compartment linear model best described the time course of tigecycline concentrations. The parameter estimates (expressed as means +/- standard deviations [SD]) from the final model were as follows: clearance (CL), 7.50 +/- 1.11 liters/h; volume in the central compartment, 72.50 +/- 21.18 liters; rate constant for tigecycline distribution from the central to the peripheral compartment, 0.31 +/- 0.16 h(-1); and rate constant for tigecycline distribution from the peripheral to the central compartment, 0.29 +/- 0.30 h(-1). A larger BMI was associated with increased CL of tigecycline. Licensed doses were found to be sufficient for Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus for an AUC(0- 24)/MIC target of 4.5 or 6.96. For a therapeutic target of 17.9, an increased tigecycline dose is required, especially for patients with higher BMI. The dosing requirements of tigecycline differ with the indication, with pathogen susceptibility, and potentially with patient BMI

Dominant Fungal Communities Aggregate in the Shallow Rhizosphere Soil of Anabasis aphylla

Rhizosphere soil microorganisms are significant factors affecting plant growth, especially that of saline–alkali tolerant plants in the desert ecosystem. We performed high-throughput sequencing in order to identifying the fungal community structures and their relationships to the physicochemical properties of different soil layers for the desert plant, Anabasis aphylla, in its natural environment. The number of unique operational taxonomic units (OTUs) found in the bulk soil of the 0–20 cm layer contributed to the biggest percentage (24.13%) of the overall amount of unique OTUs. Despite the fact that there was a rather large variety of fungi in the bulk soil of A. aphylla, the number of dominating fungi, which included Ascomycota, Microascus, and Arachnomyces, was found to be in quite high abundance in the rhizosphere soil. In the 20–40 cm layer of rhizosphere soil, the phylum Ascomycota accounted for 84.78% of the total phyla identified, whereas the species Microascus and Arachnomyces accounted for 24.72% and 37.18%, respectively, of the total species identified. In terms of the soil physicochemical properties, electric conductivity was the primary environmental component influencing the dominant fungi. The findings of this research enhance our comprehension of dominant fungi distributions and relevant environmental factors affecting the saline–alkali tolerant desert plant, A. aphylla. The results also provide a theoretical basis to help elucidate fungi adaptation mechanisms to the saline–alkali environment and methods for their isolation and screening

Dominant Fungal Communities Aggregate in the Shallow Rhizosphere Soil of <i>Anabasis aphylla</i>

Rhizosphere soil microorganisms are significant factors affecting plant growth, especially that of saline–alkali tolerant plants in the desert ecosystem. We performed high-throughput sequencing in order to identifying the fungal community structures and their relationships to the physicochemical properties of different soil layers for the desert plant, Anabasis aphylla, in its natural environment. The number of unique operational taxonomic units (OTUs) found in the bulk soil of the 0–20 cm layer contributed to the biggest percentage (24.13%) of the overall amount of unique OTUs. Despite the fact that there was a rather large variety of fungi in the bulk soil of A. aphylla, the number of dominating fungi, which included Ascomycota, Microascus, and Arachnomyces, was found to be in quite high abundance in the rhizosphere soil. In the 20–40 cm layer of rhizosphere soil, the phylum Ascomycota accounted for 84.78% of the total phyla identified, whereas the species Microascus and Arachnomyces accounted for 24.72% and 37.18%, respectively, of the total species identified. In terms of the soil physicochemical properties, electric conductivity was the primary environmental component influencing the dominant fungi. The findings of this research enhance our comprehension of dominant fungi distributions and relevant environmental factors affecting the saline–alkali tolerant desert plant, A. aphylla. The results also provide a theoretical basis to help elucidate fungi adaptation mechanisms to the saline–alkali environment and methods for their isolation and screening

Important Roles of Key Genes and Transcription Factors in Flower Color Differences of Nicotiana alata

Nicotiana alata is an ornamental horticultural plant with a variety of flower colors and a long flowering period. The genes in four different colored N. alata (white, purple, red, and lemon green) were analyzed to explain the differences in flower color using transcriptomes. A total of 32 differential expression genes in the chlorophyll biosynthesis pathway and 41 in the anthocyanin biosynthesis pathway were identified. The enrichment analysis showed that the chlorophyll biosynthesis pathway and anthocyanin biosynthesis pathway play critical roles in the color differences of N. alata. The HEMA of the chlorophyll biosynthesis pathway was up-regulated in lemon green flowers. Compared with white flowers, in the red and purple flowers, F3H, F3&prime;5&prime;H and DFR were significantly up-regulated, while FLS was significantly down-regulated. Seventeen differential expression genes homologous to transcription factor coding genes were obtained, and the homologues of HY5, MYB12, AN1 and AN4 were also involved in flower color differences. The discovery of these candidate genes related to flower color differences is significant for further research on the flower colors formation mechanism and color improvements of N. alata

HIF-1 alpha overexpression correlates with poor overall survival and disease-free survival in gastric cancer patients post-gastrectomy.

Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1α overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1α in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1α, TGF-β, VEGF and pERK1/2 in gastric cancer patients following gastrectomy.This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-β, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.HIF-1α overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, χ2 = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, χ2 = 13.691). In univariate analysis, patients with HIF-1α overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, χ2 = 74.937; OS: NA VS. 25.5 m, P = 0.000, χ2 = 90.594). Importantly, HIF-1α overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95%CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95%CI 2.663-4.667, P = 0.000).HIF-1α overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1α expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients

Lateral Flow Immunoassay Based on Time-Resolved Fluorescence Microspheres for Rapid and Quantitative Screening CA199 in Human Serum

Carbohydrate antigen 199 (CA199) is a serum biomarker which has certain value and significance in the diagnosis, prognosis, treatment, and postoperative monitoring of cancer. In this study, a lateral flow immunoassay based on europium (III) polystyrene time-resolved fluorescence microspheres (TRFM-based LFIA), integrated with a portable fluorescence reader, has been successfully establish for rapid and quantitative analysis of CA199 in human serum. Briefly, time-resolved fluorescence microspheres (TRFMs) were conjugated with antibody I (Ab1) against CA199 as detection probes, and antibody II (Ab2) was coated as capture element, and a “TRFMs-Ab1-CA199-Ab2” sandwich format would form when CA199 was detected by the TRFM-based LFIA. Under the optimal parameters, the detection limit of the TRFM-based LFIA for visible quantitation with the help of an ultraviolet light was 4.125 U/mL, which was four times lower than that of LFIA based on gold nanoparticles. Additionally, the fluorescence ratio is well linearly correlated with the CA199 concentration (0.00–66.0 U/mL) and logarithmic concentration (66.0–264.0 U/mL) for quantitative detection. Serum samples from 10 healthy people and 10 liver cancer patients were tested to confirm the performances of the point-of-care application of the TRFM-based LFIA, 20.0 U/mL of CA199 in human serum was defined as the threshold for distinguishing healthy people from liver cancer patients with an accuracy of about 60%. The establishment of TRFM-based LFIA will provide a sensitive, convenient, and efficient technical support for rapid screening of CA199 in cancer diagnosis and prognosis

Association between periodontitis and hypertension: cross-sectional survey from the Fourth National Oral Health Survey of China (2015–2016)

Objectives To evaluate the association between periodontitis severity and hypertension based on Chinese epidemiological data.Design This cross-sectional survey enrolled adults from the Fourth National Oral Health Survey of China (2015–2016).Setting The data were obtained from the Fourth National Oral Health Survey of China (2015–2016).Participants The study included individuals aged 35–44 years (n=4409), 55–64 years (n=4568) and 65–74 years (n=4218).Primary and secondary outcome measures Periodontal status, defined on the basis of the 2017 classification scheme, and periodontal parameters (eg, bleeding on probing (BOP)) were compared between individuals with hypertension and individuals with normotension. Smoothed scatterplots were constructed to demonstrate the associations of periodontal parameters and periodontal status with hypertension.Results Severe periodontitis (stages III and IV) was present in 41.4% of individuals with hypertension and 28.0% of individuals with normotension, respectively (p&lt;0.001). The prevalence of severe periodontitis was higher in individuals with hypertension than that in individuals with normotension among participants aged 35–44 years (18.0% vs 10.1%, p&lt;0.001) and 55–64 years (40.2% vs 36.7%, p=0.035), but not in participants aged 65–74 years (46.4% vs 45.1%, p=0.429). Therefore, the difference in periodontal status between individuals with hypertension and individuals with normotension decreased with age. There were higher prevalences of BOP, probing depth (PD) ≥4 mm and PD ≥6 mm in individuals with hypertension than in individuals with normotension (52.1% vs 49.2%, 19.6% vs 14.7% and 1.8% vs 1.1%, respectively). Periodontitis severity and the proportion of teeth with PD ≥4 or ≥6 mm were positively associated with hypertension.Conclusion Periodontitis is associated with hypertension in Chinese adults. Hypertension prevalence increased with periodontitis severity, particularly among young participants. Accordingly, it is necessary to improve the education, awareness of periodontal treatment and preventive management among individuals at risk of hypertension, particularly in the younger population

Immunohistochemical staining of TGF-β, HIF-1α, VEGF and pERK 1/2 expression in gastric cancer.

<p>A. Immunohistochemical staining of TGF-β was located mainly in the cytoplasm of tumor cells (positive expression ×400); B. TGF-β original magnification ×100; C. HIF-1α was located mainly in the nucleus of tumor cells (positive expression ×400); D. HIF-1α original magnification ×100; E. VEGF was located mainly in the cytoplasm of tumor cells (positive expression ×400); F. VEGF original magnification×100; G. pERK1/2 was located in the cytoplasm and nucleus of tumor cells (positive expression ×400); H. pERK1/2 original magnification ×100.</p