Objective: To study the effects of endoscopic submucosal dissection(ESD) on long-term quality of life (QOL) and gastric function of patients with distal early gastric cancer (EGC), compared with those of surgery. Methods: Patients with EGC who received ESD or surgical resection in Peking Union Medical College Hospital over 1 year ago were selected to be followed up. QLQ-C30, SF-36, EQ-5D and dyspeptic symptom rating scale were used to evaluate QOL. Five-hour gastric emptying rate was used to evaluate distal gastric function. Electronic gastroscopy was used to observe whether the anastomotic stoma was stenotic. According to the age at resection, 1 to 1 matching was performed between the distal 1/3 gastric ESD (E_P) group and the distal subtotal gastrectomy (S_P) group, and then the QOL and gastric function between the two groups were compared. Results: Twenty-five patients were included in group E_P and group S_P respectively. According to QLQ-C30, the scores of cognitive function were 83.3 (83.3, 83.3) in group E_P and 83.3 (83.3, 100.0) in group S_P (P=0.056). The proportion of patients with symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) between the two groups were not statistically different. There was no statistical difference in the scores of EQ-5D and SF-36 between the two groups. According to dyspeptic symptom rating scale, 56.0% patients in group E_Phad burning sensation, but only 28.0% in group S_P had this symptom (P=0.054). 20.0% of patients in group S_Preported nausea, while only 4.0% in group E_P had this symptom (P=0.084). Gastric emptying results showed that the proportion of patients with abnormal 5-hour gastric emptying rate was 31.8% in group E_P, while there was no abnormal emptying in group S_P (P=0.003). Gastroscopy results showed that one patient in group E_P had pyloric stenosis, but 5-hour gastric emptying rate was normal. All anastomotic stomas in group S_p were unobstructed. Conclusion ESD and surgical resection for distal EGC show similar long-term effects on QOL of patients. But the long-term gastric emptying function may decrease after distal gastric ESD.

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.

The purpose of this investigation was to develop Pluronic F-127 coated N-trimethyl chitosan nanoparticles(F-S NPs)of insulin as the model drug and asses their penetration of the mucosal barriers. Single factor screening was used to optimize the formulations of nanoparticles and the nanoparticles were characterized. Their particle size, Zeta potential, encapsulation efficiencies and drug loading were assayed to be(240. 6±6. 51)nm, (10. 42±1. 60)mV, (43. 39±2. 83)% and(3. 39±0. 57)%, respectively. The impact of PF-127 on mucin binding in vitro and nanoparticles′s transport in freshly obtained mucus were also evaluated. The mucin affinity of F-S NPs was significantly reduced when compared to that of the N-trimethyl chitosan nanoparticles(S NPs), i. e. , 28% of the latter. And F-S NPs was found to have an improved mucosal penetrating capability. Mucus-secreting HT29-MTX-E12(E12)cell monolayer was selected to investigate their cellular uptake. F-S NPs exhibited higher penetration coefficient than both free insulin and S NPs in mucus-secreting epithelium cells, i. e. , 16-fold and 1. 4-fold, respectively. Data suggest that F-S NPs be potential carriers to cross mucosal barriers and enhance the cellular uptake of insulin.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.