RESUMO
In conventional chromatographic ligand screening, underperforming ligands are often dismissed. However, this practice may inadvertently overlook potential opportunities. This study aims to investigate whether these underperforming ligands can be repurposed as valuable assets. Hydrophobic charge-induction chromatography (HCIC) is chosen as the validation target for its potential as an innovative chromatographic mode. A novel dual-ligand approach is employed, combining two suboptimal ligands (5-Aminobenzimidazole and Tryptamine) to explore enhanced performance and optimization prospects. Various dual-ligand HCIC resins with different ligand densities were synthesized by adjusting the ligand ratio and concentration. The resins were characterized to assess appearance, functional groups, and pore features using SEM, FTIR, and ISEC techniques. Performance assessments were conducted using single-ligand mode resins as controls, evaluating the selectivity against human immunoglobulin G and human serum albumin. Static adsorption experiments were performed to understand pH and salt influence on adsorption. Breakthrough experiments were conducted to assess dynamic adsorption capacity of the novel resin. Finally, chromatographic separation using human serum was performed to evaluate the purity and yield of the resin. Results indicated that the dual-ligand HCIC resin designed for human antibodies demonstrates exceptional selectivity, surpassing not only single ligand states but also outperforming certain high-performing ligand types, particularly under specific salt and pH conditions. Ultimately, a high yield of 83.9 % and purity of 96.7 % were achieved in the separation of hIgG from human serum with the dual-ligand HCIC, significantly superior to the single-ligand resins. In conclusion, through rational design and proper operational conditions, the dual-ligand mode can revitalize underutilized ligands, potentially introducing novel and promising chromatographic modes.
Assuntos
Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G , Ligantes , Humanos , Adsorção , Imunoglobulina G/química , Imunoglobulina G/sangue , Triptaminas/química , Cromatografia Líquida/métodos , Benzimidazóis/química , Concentração de Íons de HidrogênioRESUMO
Background: Colorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify correlations between gastric histopathology stages and risks of specific colorectal neoplasms, to optimize screening and reduce preventable CRC. Methods: Clinical data of 36,708 patients undergoing gastroscopy and colonoscopy from 2005-2022 were retrospectively analyzed. Correlations between gastric and colorectal histopathology were assessed by multivariate analysis. Outcomes of interest included non-adenomatous polyps (NAP), conventional adenomas (CAs), serrated polyps (SPs), and CRC. Statistical analysis used R version 4.0.4. Results: Older age (≥50 years) and Helicobacter pylori infection (HPI) were associated with increased risks of conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous polyps (NAP), and colorectal cancer (CRC). Moderate to severe intestinal metaplasia specifically increased risks of NAP and CAs by 1.17-fold (95% CI 1.05-1.3) and 1.19-fold (95% CI 1.09-1.31), respectively. For CRC risk, low-grade intraepithelial neoplasia increased risk by 1.41-fold (95% CI 1.08-1.84), while high-grade intraepithelial neoplasia (OR 3.76, 95% CI 2.25-6.29) and gastric cancer (OR 4.81, 95% CI 3.25-7.09) showed strong associations. More advanced gastric pathology was correlated with progressively higher risks of CRC. Conclusion: Precancerous gastric conditions are associated with increased colorectal neoplasm risk. Our findings can inform screening guidelines to target high-risk subgroups, advancing colorectal cancer prevention and reducing disease burden.
RESUMO
BACKGROUND: Split-dose regimens (SpDs) of 4 L of polyethylene glycol (PEG) have been established as the "gold standard" for bowel preparation; however, its use is limited by the large volumes of fluids required and sleep disturbance associated with night doses. Meanwhile, the same-day single-dose regimens (SSDs) of PEG has been recommended as an alternative; however, its superiority compared to other regimens is a matter of debate. AIM: To compare the efficacy and tolerability between SSDs and large-volume SpDs PEG for bowel preparation. METHODS: We searched MEDLINE/PubMed, the Cochrane Library, RCA, EMBASE and Science Citation Index Expanded for randomized trials comparing (2 L/4 L) SSDs to large-volume (4 L/3 L) SpDs PEG-based regimens, regardless of adjuvant laxative use. The pooled analysis of relative risk ratio and mean difference was calculated for bowel cleanliness, sleep disturbance, willingness to repeat the procedure using the same preparation and adverse effects. A random effects model or fixed-effects model was chosen based on heterogeneity analysis among studies. RESULTS: A total of 18 studies were included. There was no statistically significant difference of adequate bowel preparation (relative risk = 0.97; 95%CI: 0.92-1.02) (14 trials), right colon Boston Bowel Preparation Scale (mean difference = 0.00; 95%CI: -0.04, 0.03) (9 trials) and right colon Ottawa Bowel Preparation Scale (mean difference = 0.04; 95%CI: -0.27, 0.34) (5 trials) between (2 L/4 L) SSDs and large-volume (4 L/3 L) SpDs, regardless of adjuvant laxative use. The pooled analysis favored the use of SSDs with less sleep disturbance (relative risk = 0.52; 95%CI: 0.40, 0.68) and lower incidence of abdominal pain (relative risk = 0.75; 95%CI: 0.62, 0.90). During subgroup analysis, patients that received low-volume (2 L) SSDs showed more willingness to repeat the procedure using the same preparation than SpDs (P < 0.05). No significant difference in adverse effects, including nausea, vomiting and bloating, was found between the two arms (P > 0.05). CONCLUSION: Regardless of adjuvant laxative use, the (2 L/4 L) SSD PEG-based arm was considered equal or better than the large-volume (≥ 3 L) SpDs PEG regimen in terms of bowel cleanliness and tolerability. Patients that received low-volume (2 L) SSDs showed more willingness to repeat the procedure using the same preparation due to the low-volume fluid requirement and less sleep disturbance.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS. METHODS: This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups. RESULTS: In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers. CONCLUSIONS: This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.