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OBJECTIVE: The aim of this study was to explore the correlation between rs8069115, rs41289087, and rs11079042 polymorphisms of the signal transducer and activator of transcription 3 (STAT3) gene and chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A total of 200 patients diagnosed with COPD were enrolled in the disease group. Meanwhile, 200 normal subjects were selected as the control group. Peripheral blood was collected from subjects in the disease group and control group. Subsequently, nucleated cells were isolated for determination of STAT3 gene polymorphisms. Quantitative Polymerase Chain Reaction (qPCR) was utilized to detect the expression level of STAT3. Samples from 12 patients with differences in STAT3 haplotypes and 12 cases with no difference were collected and treated with transcriptome sequencing to analyze pathways enriched with differentially expressed genes. RESULTS: There were statistically significant differences in allele distributions at rs8069115 between the disease group and control group (p=0.000), and the allele frequency of G was higher in disease group. Genotype distributions of rs8069115 (p=0.000) and rs41289087 (p=0.000) of the STAT3 gene in disease group were significantly different in comparison with the control group. The frequency of rs8069115 GG genotype was remarkably higher, while the frequency of rs41289087 TG genotype was lower in the disease group (p<0.05). In addition, compared with the control group, the distributions of the dominant model (p=0.002) and recessive model (p=0.004) of rs8069115 of the STAT3 gene were markedly different in the disease group. A significantly higher frequency of dominant model GG+GA and lower frequency of recessive model GA+AA were observed at rs8069115 in the disease group (p<0.05). Moreover, the haplotype distributions of AGC (p=0.002), ATC (p=0.001), GTA (p=0.010), and GTC (p=0.035) at rs8069115, rs41289087, and rs11079042 were different between the disease group and control group. Besides, rs8069115 locus and rs11079042 locus were linked to each other (D’=0.523). There was a remarkable association between rs11079042 polymorphism of the STAT3 gene and gene expression (p<0.05). STAT3 was highly expressed in patients with genotype CC (p<0.05). Furthermore, changes in transcriptome levels among different haplotype populations (haplotype with different distributions vs. haplotype with no difference in distribution) were analyzed. The results demonstrated that multiple pathways, such as ECM-receptor interactions, cell cycle checkpoints, and protein processing were notably enriched (p<0.05). CONCLUSIONS: According to our results, we confirmed that the polymorphisms (rs8069115, rs41289087, and rs11079042) of STAT3 gene are noticeably correlated with the occurrence and progression of COPD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Previous studies have demonstrated that urinary kidney injury molecule-1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL) were superior to serum creatinine (Scr) in detecting acute kidney injury (AKI), but their ability to predict clinical vancomycin-associated AKI has not been investigated. This study aimed to investigate the abilities of uKIM-1 and uNGAL individually and in combination to predict vancomycin-associated AKI. PATIENTS AND METHODS: Scr, uKIM-1, and uNGAL were measured on the day before and days 1, 2, and 3 of vancomycin therapy in a generalized adult population. Levels of these biomarkers between AKI and non-AKI groups were comparatively analyzed. Predictive performances were evaluated by receiver operating characteristic curve (ROC) analysis. RESULTS: A total of 87 patients were enrolled, and among them, 11 (12.6%) patients developed AKI. Urinary KIM-1 and NGAL levels in the AKI group were higher than in the non-AKI group at all time points (p < 0.05), and the areas under the receiver operating characteristic curves (AUC) were 0.849 (95% confidence interval [CI] 0.750-0.948) for uKIM-1 and 0.824 (95% CI 0.726-0.922) for uNGAL, with cut-off values of 1.72 ng/mL and 9.07 ng/mL respectively. The AUC of uKIM-1 and uNGAL combined was 0.852 (95% CI 0.754-0.949), and the sensitivity and specificity were 90.9% and 75.0%, respectively. CONCLUSIONS: Urinary KIM-1 and NGAL could efficiently discriminate patients with or without vancomycin-associated AKI earlier than Scr, and the combined urinary biomarkers showed fair discrimination compared with the individual biomarkers. [ABSTRACT FROM AUTHOR]

Uniaxial hot tensile tests were carried out in order to investigate the superplastic deformation of laser welded Ti-6Al-4V sheet. The results revealed that the welded specimens had good superplasticity at temperature of 870-920°C and strain rate of 10-3-10-2 s-1, and the elongation was 233-397%. Dynamic globularisation was observed in the weld bead, and the acicular structure of weld bead was transforming into equiaxed grains while straining. The increasing temperature and decreasing strain rate enhanced the globularisation process. [ABSTRACT FROM AUTHOR]

Objective: To explore the influence of the 4th revised treatment recommendations in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)-induced nephrotoxicity and MTX blood concentrations. Method: The clinical data from 330 ALL children who received 1 242 courses of HD-MTX therapies from September 2012 to November 2016 was collected. The courses were divided into two groups based on the chemotherapies: original scheme group was treated with the 3rd revised regimen, and new scheme group was treated with the 4th revised regimen. The two groups in acute kidney injury (AKI) and MTX blood concentrations were compared. Result: The incidences of AKI with low risk (LR) and intermediate risk (IR) in new scheme group were significantly lower than those in original scheme group (1.3%(3/229) vs . 7.9%(24/303), 4.9%(10/204) vs . 12.8%(26/203), χ(2)=11.831 and 7.888 respectively, both P <0.05). There was no significant difference in the incidence of AKI with high risk (HR) in the two groups (15.2%(10/66) vs . 10.5%(25/237), χ(2)=1.071, P >0.05). The 48h MTX blood concentrations and the interphase from onste to MTX concentrations decreased to the safe level with LR and IR children in new scheme group were significantly lower than those in original scheme group (0.36(0.08-4.00) vs . 0.44(0.06-32.00) μmol/L, 0.49(0.22-33.00) vs . 0.60(0.18-83.00) μmol/L, 3(2-6) vs . 3(2-11) d, 3(2-11) vs . 3(2-19) d, Z =-5.953, -2.658, -4.490 and -4.729 respectively, all P <0.05). The differences with HR were not observed between the two groups (0.61(0.14-36.00) vs . 0.71(0.11-68.00) μmol/L, 3(2-15) vs . 3(2-13) d, Z =-1.465 and -1.179 respectively, both P >0.05). Conclusion: Decreased renal toxicity and acceleration of MTX excretion may occur when childhood ALL with LR and IR were treated with the 4th revised regimen. However, nephrotoxicity and MTX blood concentrations have no significant differences with HR in the two regimens, and close monitoring are necessary.

Aim: To study the effects of huperzine A on nucleus basalis magnocellularis (NBM) lesion-induced spatial working memory impairment., Methods: A delayed-non-match-to-sample radial arm maze task was used to study spatial working memory. The choline acetyltransferase (ChAT) activity was determined by the conversion of [3H]acetyl-CoA to [3H]ACh., Results: Unilateral NBM lesion by kainic acid 0.02 mumol impaired rat's ability to perform this working memory task as evidenced by fewer correct choices after different delay intervals and more total errors to complete the task. This behavioral impairment associated with a decrease in the activity of ChAT by about 40% in the ipsilateral cerebral cortex. Huperzine A (0.2 mg.kg-1 i.p. 30 min before testing) ameliorated this spatial working memory impairment. Physostigmine (0.2-0.3 mg.kg-1 i.p. 20 min before testing) also attenuated the NBM lesion-induced memory deficit., Conclusion: The integrity of NBM is critical for spatial working memory processing, and this working memory impairment induced by NBM lesion can be ameliorated by huperzine A and physostigmine.

The effects of huperzine A on memory impairments induced by scopolamine were evaluated using a radial maze task and inhibition of cholinesterase in vitro compared with the effects of E2020 and tacrine. Scopolamine (0.2 mg kg-1) significantly impaired spatial memory in rats. Huperzine A (0.1-0.4 mg kg-1, p.o.), E2020 (0.5-1.0 mg kg-1, p.o.) and tacrine (1.0-2.0 mg kg-1, p.o.) could reverse these scopolamine-induced memory deficits. The ratios of huperzine A, E2020 and tacrine for butyrylcholinesterase:acetylcholinesterase determined by a colourimetric method were 884.57, 489.05, and 0.80, respectively. The results demonstrated that huperzine A was the most selective acetylcholinterase inhibitor, and improved the working memory deficit induced by scopolamine significantly better than did E2020 or tacrine, suggesting it may be a promising agent for clinical therapy of cognitive impairment in patients with Alzheimer's Disease.

The pharmacokinetics and pharmacodynamic effects of two doses of norethisterone (5mg and 3mg) used as a 'visiting pill' were investigated. There were no significant differences in the pharmacokinetics of the two doses except for the peak concentration achieved and the bioavailability as assessed by the area under the serum norethisterone concentration - time curve. Both doses were rapidly absorbed. Pharmacodynamic effects were minor. No change occurred in serum concentrations of total cholesterol, total triglycerides or HDL-cholesterol. The area under the serum glucose concentration--time curve and particularly the area under the serum insulin concentration--time curve were significantly increased as a result of treatment but no change occurred in the serum levels of glycosylated haemoglobin. SHBG concentrations in serum decreased on treatment whereas those of ceruloplasmin increased.