Oxidative stress has been suggested to play a key role in multiple sclerosis (MS), but clinical data on oxidative stress markers in MS patients were inconsistent. This study sought to quantitatively summarize the data of oxidative stress markers in the blood and cerebrospinal fluid (CSF) of patients with MS in the literature. We conducted a systematic search of PubMed and Web of Science and included studies if they provided data on the concentrations of oxidative stress markers in the peripheral blood and CSF of MS patients and healthy control (HC) subjects. The systematic search resulted in the inclusion of 31 studies with 2,001 MS patients and 2,212 HC subjects for meta-analysis. Random-effects meta-analysis demonstrated that patients with MS had significantly increased concentrations of blood oxidative stress markers compared with HC subjects for malondialdehyde (MDA; Hedges' g, 2.252; 95% CI, 1.080 to 3.424; p < 0.001) and lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH; Hedges' g, 0.383; 95% CI, 0.065 to 0.702; p = 0.018). In contrast, concentrations of albumin (Hedges' g, −1.036; CI, −1.679 to −0.394; p = 0.002) were significantly decreased in MS patients when compared with those in HC subjects. However, the other analyzed blood oxidative stress markers did not show significant differences between cases and controls. Furthermore, this meta-analysis showed significant association between CSF MDA and MS (Hedges' g, 3.275; 95% CI, 0.859 to 5.691; p = 0.008). Taken together, our results revealed increased blood and CSF MDA and decreased blood albumin levels in patients with MS, strengthening the clinical evidence of increased oxidative stress in MS.

Background: To investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model. Methods: A pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested. Results: The area under the curve (AUC; 0-T, 300.342 ± 35.832 mg/L* h; AUC 0-∞, 320.462 ± 40.213 mg/L* h), the plasma peak concentration (30.622 ± 9.917 mg/L*), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05). Conclusion: TCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.

4069 Background: Esophageal and gastric cancer (EC and GC) are two common cancer types that severely impact patients’ health. The 5-year survival rate for EC and GC is as low as 19% and 31%, respectively. However, early detection will significantly increase the survival rate: stage-1 EC has a 5-year survival rate of 51%, while for stage-1 GC it’s 69%. Invasive screening methods, such as endoscopy and biopsy, caused low compliance. Computational tomography and carcinoembryonic antigen were limited by low sensitivity. To address this problem, we developed GaEsSeer, a non-invasive targeted-sequencing-based assay that utilizes multiple methylation and fragmentomics features of cell-free DNA (cfDNA) to accurately detect EC and GC signals in blood. Methods: cfDNA was tested using the GaEsSeer panel, which was developed using in-house genome-wide sequencing data on EC and GC samples, and public datasets from databases and literature. Methylation features, which was quantified as methylation haplotypes or methylation encoding score, and fragmentomics features including copy number and end motif ratio were taken for modeling. Separate sub-models were trained utilizing each type of feature, which were eventually combined via logistic regression to establish the final predicting model. Results: A total of 1770 participants were recruited from multiple centers. This included 787 healthy individuals, 448 cancers (209 EC, 239 GC; stage I:156, -II:120, -III:78, and -IV:58), 174 benign esophageal diseases, and 361 benign gastric diseases. For cancer detection, the methylation-only model had an AUC of 0.909 and 0.897 in training (618 total) and test sets (617 total), respectively; while the AUC of the fragmentomics-based model was 0.885 and 0.911, respectively. The combinatorial model further improved performances, which achieves an AUC of 0.940 and 0.931 in the training and test cohorts, respectively. While the specificity remained at 96.7%, GaEsSeer detected 81.1% EC and 70.3% GC cases in the test cohort. It had a sensitivity of 74.2% and 48.9% for stage-I EC and GC, respectively. GaEsSeer also has high specificities of 87.9% and 89.8% for benign esophageal and gastric diseases, respectively. Additionally, the performance of GaEsSeer was compared with known serum cancer markers such as CEA, CA19-9, and CA72-4; and the results show that it had significantly higher sensitivity than any of these serum markers (54.8% vs 6.4% when against CEA; 53.5% vs 7.1% when against CA19-9; 50% and 16.7% when against CA72-4). Conclusions: In this pilot study, we developed the blood-based GaEsSeer assay and a model for EC and GC detection with high accuracy by stacking multiple methylation- and fragmentomics-based submodules together. Further optimization and validation of GaEsSeer using larger prospective cohorts are needed to validate its potentials for clinical application.