A novel inflammation-related prognostic biomarker for predicting the disease-free survival of patients with colorectal cancer.

BACKGROUND: To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients. METHODS: A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs). RESULTS: During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32-0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making. CONCLUSIONS: Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.

Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis.

BACKGROUND: EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. METHODS: The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. RESULTS: HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). CONCLUSION: Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

Controllable Synthesis of Titanium Silicon Molecular Zeolite Nanosheet with Short b-Axis Thickness and Application in Oxidative Desulfurization.

Titanium silicon molecular zeolite (TS-1) plays an important role in catalytic reactions due to its unique nanostructure. The straight channel on TS-1 was parallel to the orientation of the short b-axis and directly exposed to the aperture of the 10-member ring with a diameter of 0.54 nm × 0.56 nm. This structure could effectively reduce the diffuse restriction of bulk organic compounds during the oxidative desulfurization process. As a kind of cationic polymer electrolyte, polydimethyldiallyl ammonium chloride (PDDA) contains continuous [C8H16N+Cl-] chain segments, in which the Cl- could function as an effective structure-directing agent in the synthesis of nanomaterials. The chain of PDDA could adequately interact with the [0 1 0] plane in the preparation process of zeolite, and then the TS-1 nanosheet with short b-axis thickness (6 nm) could be obtained. The pore structure of the TS-1 nanosheet is controlled by regulating the content of PDDA. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 physical adsorption analysis, infrared absorption spectrum and ultraviolet-visible spectrum were used to determine the TS-1. The thinner nanosheets exhibit excellent catalytic performance in oxidative desulfurization of dibenzothiophene (DBT), in which the removal rate could remain at 100% after three recycles. Here, the TS-1 nanosheet with short b-axis thickness has a promising future in catalytic reactions.

Effects of exposure to the explosive and environmental pollutant 2,4,6-trinitrotoluene on ovarian follicle development in rats.

Although 2,4,6-trinitrotoluene (TNT) is a dangerous carcinogen in environmental pollution, information on the reproductive effects of TNT explosive contamination is limited. To explore the possible ovarian effects, TNT explosive-exposed rat models were established, and Wistar female rats were exposed to low and high TNT (40 g and 80 g, air and internal) explosives. After a month of exposure, the estrous cycle, ovarian histopathology, and follicle counting were conducted. Serum hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, testosterone, and estradiol were detected, and the mRNA and protein expression of steroidogenic enzymes were measured. The results showed that the diestrus phase duration was significantly (P < 0.05) increased in the high TNT-exposed groups. In addition, the proportions of preantral follicles were significantly (P < 0.05) decreased in the high TNT-exposed groups, as well as the proportions of atretic follicles. The serum estradiol levels were significantly (P < 0.05) increased, and the follicle-stimulating hormone and luteinizing hormone levels were significantly (P < 0.05) decreased in the high TNT-exposed groups. The mRNA levels of steroidogenic acute regulatory protein (Star), cytochrome P450 cholesterol side chain cleavage (Cyp11a1, Cyp17a1 and Cyp19a1), hydroxysteroid dehydrogenase 3b (Hsd3b) and steroidogenic factor-1 (SF-1) were significantly (P < 0.05) increased in the TNT-exposed groups. The protein levels of Star, Cyp11a1 and Hsd3b were increased (P < 0.05) in the TNT-exposed groups. These results indicate that the exposure of rats to TNT explosive can subsequently affect ovarian follicle development, suggesting that the mechanism may involve disrupting steroidogenesis.

Bending and Crack Evolution Behaviors of Cemented Soil Reinforced with Surface Modified PVA Fiber.

To improve the flexural properties of cemented soils reinforced with fibers and avoid their brittle failure when subjected to complex loading conditions, a simple and cost-effective technique was explored to facilitate their application in retaining walls. In this study, how different fiber surface modifications, i.e., alkali treatment, acid treatment and silane coupling agent treatment, as well as different fiber contents, i.e., 0%, 0.25%, 0.5% and 1%, affect the bending properties of cemented soils was investigated by conducting three-point bending tests on notched beams. The digital image correlation (DIC) technology was used to examine the crack propagation process and the strain field distribution of cracks in specimens in the flexural tests. The results show that all fiber surface modifications increased peak strength and fracture energy, for example, the fracture energy of specimens AN1, AH1 and AK1 was increased by 180.4%, 121.5% and 155.4%, respectively, compared to PVA1. In addition, the crack tip strain, crack propagation rate and the initial crack width of the modified specimens were lower than those before modification. Lastly, scanning electron microscope (SEM) and mercury intrusion porosimetry tests were adopted to reveal the mechanism of bending performance in cemented soils reinforced by fiber surface modifications.

Correlations of Moesin expression with the pathological stage, nerve infiltration, tumor location and pain severity in patients with pancreatic cancer.

PURPOSE: The study aimed to investigate the correlations of the expression of membrane-organizing extension spike protein (moesin) with the pathological stage, nerve infiltration, tumor location and pain severity in patients with pancreatic cancer (PC) and analyze its possible mechanism. METHODS: A total of 43 patients with pancreatic cancer receiving surgical resection in our hospital were enrolled, with the adjacent tissues as controls. Then, quantitative polymerase chain reaction (qPCR) and Western blotting were carried out to measure the expression level of the moesin messenger ribonucleic acid (mRNA) in PC tissues. The expression levels of matrix metalloproteinase-7 (MMP-7), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-10 (IL-10) in PC tissues were detected using enzyme-linked immunosorbent assay (ELISA) kit. The relationship between moesin and the pathological stage of patients was analyzed, followed by further analyses on the correlations of moesin with nerve infiltration, tumor location and pain severity of patients with PC. RESULTS: The results of qPCR and Western blotting demonstrated that the expression levels of the moesin mRNA and moesin in PC tissues were evidently higher than those in adjacent tissues (p<0.01). Based on ELISA, the expression levels of MMP-7, TNF-α and IL-6 (p<0.01) were significantly higher, while the expression level of IL-10 (p<0.01) was obviously lower in PC tissues compared with those in adjacent tissues. The expression of moesin was closely associated with the pathological stage of patients with PC (p<0.01). The expression level of moesin in PC tissues in patients with nerve infiltration was significantly higher than that of those without nerve infiltration (p<0.01). It was distinctly elevated in PC tissues of patients with tumors located in the tail of the pancreas in comparison with those with tumors located in the head of the pancreas (p<0.01). The pain severity was correlated with the expression level of moesin in PC tissues (p<0.01). CONCLUSION: Moesin affects the progression of PC by activating MMP-7 and further promoting the release of TNF-α and IL-6 and decreasing the level of IL-10. The expression of moesin in PC tissues has close relations with the pathological stage of the disease, nerve infiltration, tumor location and pain severity.

Cofilin 2 in Serum as a Novel Biomarker for Alzheimer's Disease in Han Chinese.

The identification of biomarkers of Alzheimer's disease (AD) is an important and urgent area of study, not only to aid in the early diagnosis of AD, but also to evaluate potentially new anti-AD drugs. The aim of this study was to explore cofilin 2 in serum as a novel biomarker for AD. The upregulation was observed in AD patients and different AD animal models compared to the controls, as well as in AD cell models. Memantine and donepezil can attenuate the upregulation of cofilin 2 expression in APP/PS1 mice. The serum levels of cofilin 2 in AD or mild cognitive impairment (MCI) patients were significantly higher compared to controls (AD: 167.9 ± 35.3 pg/mL; MCI: 115.9 ± 15.4 pg/mL; Control: 90.5 ± 27.1 pg/mL; p < 0.01). A significant correlation between cofilin 2 levels and cognitive decline was observed (r = -0.792; p < 0.001). The receiver operating characteristic curve (ROC) analysis showed the area under the curve (AUC) of cofilin 2 was 0.957, and the diagnostic accuracy was 80%, with 93% sensitivity and 87% specificity. The optimal cut-off value was 130.4 pg/ml. Our results indicate the possibility of serum cofilin 2 as a novel and non-invasive biomarker for AD. In addition, the expression of cofilin 2 was found to be significantly increased in AD compared to vascular dementia (VaD), and only an increased trend but not significant was detected in VaD compared to the controls. ROC analysis between AD and VaD showed that the AUC was 0.824, which could indicate a role of cofilin 2 as a biomarker in the differential diagnosis between AD and VaD.

Valproate acid (VPA)-induced dysmetabolic function in clinical and animal studies.

BACKGROUND: Valproate acid (VPA), a commonly used antiepileptic medicine, is found to be linked to developing dysmetabolic risk. However, the proposed mechanism remains completely unknown. METHODS: In this study, we collected data from patients with epilepsy and further investigated the preclinical study in mice. RESULTS: As results, the clinical data showed that VPA-used patients resulted in higher levels of blood glucose, urine acid, triglyceride (TG), and immune cells (leucocyte, neutrophil leucocyte) when compared to clinically diagnosed references, while circulating apolipoprotein A1 (Apob A1) and fatty acid binding protein 4 (FABP4) were reduced without visible drug-induced liver injury (DILI). In rodent study, short-term treatment of VPA to mice showed developing trend of metabolic dysfunction, as revealed in increased serum insulin and free fatty acid and TG, and decreased liver TG content. As shown in immunoassay, FABP4 of epididymal white adipose tissue (eWAT) was down-regulated dose-dependently. CONCLUSION: Collectively, our present findings indicate that VPA can induce FABP4-impaired lipid dysmetabolism without DILI. More notably, FABP4 may function as a sensitive indicator for VPA-induced metabolic dysfunction.