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Objective:To study the effects of broad-spectrum antibiotics and induced antibiotic-resistant bacteria on the efficacy of 5-fluorouracil (5-FU) chemotherapy for mice with colon cancer and to investigate the underlying mechanisms associated with anti-tumor immune responses.Methods:BALB/c mice were subcutaneously injected with CT26 colon cancer cells and randomized into four groups: tumor-bearing control group, antibiotic group treated with ampicillin, streptomycin and colistin, 5-FU group and anitibiotic+ 5-FU group. Tumor volumes and body weights were measured and recorded. Seven days after the last 5-FU treatment, the percentages of splenic immune cell subpopulations and proliferated CD8 + T cells after co-culturing with CT26 were analyzed by flow cytometry. Gut microbiota composition was detected by 16S rRNA sequencing and the bacteria in mesenteric lymph nodes (mLN) were isolated and cultured. Bone marrow-derive macrophages were stimulated with identified bacteria and the expression of M1 and M2 polarization markers were assessed by quantitative PCR. The proliferation of CD8 + T cells co-cultured with bacteria-treated macrophages was analyzed by flow cytometry. In addition, tumor-bearing mice were treated with 5-FU and oral gavage of bacteria isolated from antibiotic+ 5-FU group or PBS. Tumor volumes, gut microbiota composition and the percentages of proliferated CD8 + T cells co-cultured with CT26 were assessed. Results:Tumor volumes were larger and body weights were lower in the antibiotic+ 5-FU group than in the 5-FU group. The percentages of CD4 + T cells, CD8 + T cells and neutrophils did not varied significantly after using antibiotics, however, the percentage of monocytes was increased in the antibiotic group. The percentage of proliferated tumor-specific CD8 + T cells in the antibiotic+ 5-FU group was decreased compared with that in the 5-FU group. Compared with the control group and 5-FU group, antibiotic usage was associated with the changes in gut microbiota composition with decreased α diversity indexes. Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis were isolated from mLNs of the antibiotic group, 5-FU group and antibiotic+ 5-FU group, respectively. Bone marrow-derived macrophages stimulated with Proteus mirabilis expressed arginase at a high level, which was a M2 polarization marker of macrophage, and associated with the decreased percentage of proliferated CD8 + T cells after co-culturing. Bacteria of the genus Proteus were enriched in the gut microbiota of 5-FU-treated tumor-bearing mice with the oral gavage of Proteus mirabilis. Although no significant inhibitory effect on tumor growth was observed, the oral gavage of Proteus mirabilis was associated with the decreased percentage of proliferated tumor-specific CD8 + T cells in vitro. Conclusions:Broad-spectrum antibiotics inhibited the efficacy of chemotherapy and the proliferation of tumor-specific CD8 + T cells, in which antibiotic-resistant bacteria might be involved.
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OBJECTIVE@#To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord.@*METHODS@#The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time.@*RESULTS@#The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6).@*CONCLUSIONS@#etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.
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Animals , Rats , Animals, Newborn , Etomidate , Neurons , Patch-Clamp Techniques , Spinal CordABSTRACT
Objective To develop cadres' stress scale for the Chinese people' s armed police forces.Methods Based on the stress theory and principles of the psychometrics,combined with characteristics of armed police forces. The cadres' stress scale was developed by ourselves. 802 cadres were evaluated as samples and statistic the data by item analysis ,factor analysis, reliability and valid analysis. Results The scale included four dimensions: task stress, economy stress, interpersonal stress and development stress. The internal consistency reliability was 0.893 ,the split-half reliability coefficient was 0.812. Retest reliability coefficient was 0.813. The criterion related validity to the stress scale and SCL-90 was good and the correlation coefficient with somatization, anxiety,depression, interpersonal sensitivity was 0. 376,0. 383,0. 396,0. 387 individually (P < 0.05 ). Conclusion Cadres stress scale for cadres of Chinese people's armed police forces has good reliability and validity.
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Objective To investigate the RADIL mRNA expression in pancreatic carcinoma and to evaluate its clinical significance.Methods Fluoesecent quantitative PCR (FQ-PCR) was used to detect the RADIL mRNA expression in 40 patients with pancreatic carcinoma and adjacent tissue and in 5 healthy adult with normal pancreatic tissue and to observe its relationship with clinicopathologic parameters.Results RADIL mRNA was expressed in pancreatic carcinoma and adjacent tissue, as well as normal pancreatic tissue, and the relative expression was 2.263 ± 3.826, 5.425 ± 8.858 and 8.559 ± 4.214, respectively.There was statistically significant difference among the three groups (P <0.05 ).RADIL mRNA expression was closely related with the metastasis and differentiation grade ( r = -0.312 and -0.294, P < 0.05 ), however, it was not significantly related to tumor site, tumor size, CA19-9, TNM staging, sex and age.Conclusions RADIL gene may have an inhibitory effect on the pancreatic cancer.
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Objective To detect the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in mice with acute necrotizing pancreatitis (ANP). Methods Male kunming mice (n = 50) were randomly divided to control group, ANP 24, 48, 72, 96 h group. ANP model was induced by intraperitoneally injection with 20% L-arginine at a dose of 4 mg/g each, 1 h apart. Mice in control group received intraperitoneally injections of same amount of normal saline. Serum amylase, creatinine, and ALT were examined and pathological evaluation of pancreatic tissues was performed. The expression of TREM-1 mRNA in peripheral blood leucocyte was determined by RT-PCR. The expression of TREM-1 protein in pancreatic tissue was detected by immunohistochemistry. Results Serum amylase, creatinine, and ALT in ANP 24 h were (9439 ± 1273)U/L, (84.8 ±75.9) μmol/L, ( 158.1 ± 122. 1 ) U/L, which were significantly higher than those in control group [ ( 2412 ± 297 ) U/L, (29.2 ± 19. 1 ) μmol/L, (41.4 ± 7.9 ) U/L) ]. The pathological scores of the pancreas in ANP group increased corresponding to time. The expressions of TREM-1 mRNA in ANP 24, 48,72, 96 h group were 15.55, 30.36, 15.77, 28.32, and the expressions of TREM-1 mRNA in ANP 48 h group was significantly higher than that in other groups ( P <0.01 ). The expressions of TREM-1 protein in the pancreas did not significantly change corresponding to time. Conclusions TREM-1 may be involved in the development of ANP by triggering other inflammatory factors.
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This paper introduced the nursing care of an elderly patient with severe pemphigus complicated with septicemia,such as specialized skin care,treatment with hormones and antibiotics,observation of drug effects,as well as hemoculture,nutrition and psychological care.The patient cooperated well with clinical treatment and was discharged with recovery 37 days later.
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Triggering receptor expressed on myeloid cells-1(TREM)-1,a recently identified molecule,is involved in monocytic activation and inflammatory responses.TREM-1 is a member of natural killer cell receptor family and is expressed on neutrophils,mature monocytes and macrophages,and it can enhance the inflammatory responses mediated by Toll-like receptor-2 and -4,showing a role of inflammation promotion.Reportedly sTREM-1 was detectable in the body fluids in the presence of bacterial or fungal infection; therefore it might be used as a marker for inflammation.In addition,recombinant sTREM-1 may also be a new method for anti-inflammatory therapy.Recently,it has been found that TREM-1 not only promoted the acute inflammatory responses,but also participated in the development of chronic inflammation.This review summarizes the role of TREM-1 in the inflammation-associated dieases.