To examine brain damage following different degrees of acute normovolemic hemodilution combined with controlled hypotension (ANH-CH) by neuronal morphological analysis and investigate the expression of nuclear factor-kappa B (NF-kappaB) activity and tumor necrosis factor-alpha (TNF-alpha) in the rat.Forty rats were randomly assigned to receive a sham operation or ANH-CH (with hematocrit 30%, 25%, 20%, and 15%). ANH was performed after baseline physiological parameters had been monitored for 20 minutes. CH was induced 30 minutes later using sodium nitroprusside and mean arterial pressure was maintained at 50-60 mm Hg for 1 hour. Rats were euthanatized 3 and a half hours after operation. TNF-alpha levels and NF-kappaB activities in cerebral temporal cortex were measured. Ultrastructural alterations in the CA1 region of the rat hippocampi were observed. Changes in mitochondria were evaluated semiquantitatively.Marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the CA1 region of the hippocampus in the ANH-CH hematocrit 20% group and ANH-CH hematocrit 15% group. TNF-alpha expression and NF-kappaB activity in the cerebral temporal cortex significantly increased in all ANH-CH groups and peaked in the ANH-CH hematocrit 25% group.Severe ANH-CH with hematocrit < or =20% may induce cerebral damage and should be avoided. NF-kappaB activation and TNF-alpha expression may play a functional role under the ischemic condition. A better understanding of the role of NF-kappaB and TNF-alpha in the brain may lead to a novel approach for preventing and treating various neurological disorders.
This study sought to investigate osteosarcoma property changes after neoadjuvant chemotherapy and to analyze any correlation between changes with phospho-AKT (p-AKT) and heat shock protein 70 (HSP70) expression in osteosarcoma cells. Thirty patients with osteosarcoma treated at Liaocheng People's Hospital between January and October, 2016 were given an imaging examination before and after neoadjuvant chemotherapy to examine osteosarcoma tumor properties, with images scored. Immunohistochemistry was used to determine p-AKT and HSP70 expression levels, as well as tumor cell necrosis rate (TCNR), in specimens obtained before and after chemotherapy. The correlation between the imaging changes of osteosarcoma after chemotherapy and the expressions of p-AKT and HSP70 in tumor cells. Compared with pre-chemotherapy, the imaging scores of the 30 patients significantly increased after chemotherapy (P<0.05). The radiographic score of the TCNR ≥90% group was 11.3±0.5, which was significantly higher than that of the TCNR <90% group (8.7±0.3, P<0.05). p-AKT expression in osteosarcoma cells was found in 13.3% of samples (4/30 cases) after chemotherapy, which was significantly lower than prior to chemotherapy (73.3%, 22/30 cases, P<0.05). After chemotherapy, HSP70 expression in osteosarcoma cells was found in 6.7% of samples (2/30 cases), which was significantly lower than prior to chemotherapy (83.3%, 25/30 cases, P<0.05). p-AKT and HSP70 expression levels were found to be correlated with TCNR after chemotherapy (P<0.05). After chemotherapy, p-AKT and HSP70 expression levels demonstrated a positive correlation with TCNR. Tumor property changes, as uncovered by imaging, were significantly inversely correlated with tumor cell p-AKT and HSP70 expression after chemotherapy. Therefore, osteosarcoma properties, as determined through X-ray imaging, were closely related to p-AKT and HSP70 expression in osteosarcoma cells after neoadjuvant chemotherapy. The effect of chemotherapy can be evaluated by observing the above examination results.
The Helankou petroglyphs offer precious data for understanding the lifeways of ancient pastoralists. However, in Helankou, the combination of unique climate conditions and complex hydrochemical environments has accelerated the weathering of the sandstone-petroglyph carriers, leading to numerous petroglyphs at risk of vanishing. In response, this study employed freeze-thaw and wet-dry cycle experiments to simulate the actual environmental conditions for sandstone. Subsequently, the sandstone that underwent the experiments was subjected to further testing and analysis. The goal was to comprehensively understand the performance change patterns and micro-mechanisms in sandstone under environmental stress, thus providing scientific theoretical support for Helankou petroglyph conservation. The results indicate that under the effects of freeze-thaw and wet-dry, the degradation processes can be attributed to a diverse combination of mechanisms such as swelling-shrinkage, hydrolysis, frost heave, dissolution, and salt crystallization, which alter the physical parameters, particle size distribution, mineral composition, and structural integrity of the sandstone.
Snail, a potent repressor of E-cadherin expression, plays a key role in epithelial-to-mesenchymal transition (EMT) in epithelial cancer. Recently, EMT and stemness programs are found linked together. In the current study, the expression of Snail and its contribution to cancer stem cell (CSC) marker expression, invasiveness, self-renewal, clonogenicity, and tumorigenicity of pancreatic cancer cells were studied. Our results showed that Snail was highly expressed in CSChigh cell line Panc-1. Stable, short hairpin RNA (shRNA)-mediated Snail knockdown decreased invasion in Panc-1 cells, in line with increased E-cadherin expression and its translocation from the nucleus to the membrane. Snail silencing in Panc-1 also inhibited CSC marker ALDH expression, together with decreased sphere and colony forming capacity, which was highly consistent with the expression of stem cell associated transcription factors like Sox2 and Oct4. In mouse xenograft models, knockdown of Snail led to a reduced number of tumor-bearing mice and a reduced average size of tumors, which had a stronger membrane staining of E-cadherin and lighter staining of Oct4. Collectively, these findings implicate Snail is required for the maintenance of stem cell-like phenotype in pancreatic cancer, and inhibition of Snail could be an efficient strategy to treat pancreatic cancer by targeting CSCs.
To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice.A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, 100 and 200 mug/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, atropine was given at 1 mg/kg 15 min before the ghrelin injection for each measurement. The mice in each group were sacrificed 20 min later and their stomachs, intestines, and colons were harvested immediately. The amount of phenol red was measured. Percentages of GE, IT, and CT were calculated.Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice (22.9 +/- 1.4 vs 28.1 +/- 1.3, 33.5 +/- 1.2 vs 43.2 +/- 1.9, 29.5 +/- 1.9 vs 36.3 +/- 1.6, P < 0.05). In the diabetic mice, ghrelin improved both GE and IT, but not CT. The most effective dose of ghrelin was 100 mug/kg and atropine blocked the prokinetic effects of ghrelin on GE and IT.Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.
A 22‐year‐old woman with an initial diagnosis of ‘ruptured ectopic pregnancy’ and ‘hemorrhagic shock’ was sent to the operation room for surgical treatment. The mucocutaneous color was deeply cyanosed and the pulse oximeter oxygen saturation (SpO 2 ) was only 86% after tracheal intubation (100% O 2 ). ‘Chocolate‐brown’ blood was observed and methemoglobinemia was considered. Then the arterial blood gas (ABG) sample was obtained, an intravenous infusion of methylene blue and vitamin C followed. The patient recovered quickly, and later two other patients with similar symptoms were treated in the same way. The success was due to a correct diagnosis accompanied with prompt treatment and quick recognition of the etiology.
The present study aimed to isolate a potential antagonist Bacillus sp. and evaluate its capacity for controlling pathogenic Vibrio parahaemolyticus in aquaculture.Strain JK08, which showed inhibitory activity against V. parahaemolyticus VP02r, was isolated from a Penaeus vannamei pond. Based on morphological, physiological, and biochemical characteristics and phylogenetic analysis, strain JK08 was identified as Bacillus sp. Through culture condition optimization, the maximal inhibition zone diameter (18.19 ± 0.16 mm) was observed when strain JK08 was cultivated at a temperature of 30°C, pH of 7, and salinity of 20‰ in Luria-Bertani broth for 24 h. The inhibition zone against V. parahaemolyticus VP02r of strain JK08 (∼7 μg, in mass of crude antimicrobial substance, per tablet) was larger than those (14-18 mm in diameter) of several commercial antibiotics (10 μg per tablet) in the in vitro antagonism assay. Liquid chromatography-tandem mass spectrometry analysis results indicated the presence of three families of lipopeptides in the antimicrobial substance: surfactin (C12-C17), iturin A (C14-C17), and fengycin A (C14-C17) and B (C17), which might be the key components contributing to the antagonistic activity of strain JK08.Strain JK08, which is capable of producing antibacterial lipopeptides, shows effective antagonistic activity against V. parahaemolyticus VP02r, implying its promising potential for V. parahaemolyticus control in aquaculture.
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