Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

An excellent assistant for robotic radical gastrectomy can play an important role in the operation, especially in a initial team. In robotic gastric cancer surgery, an excellent assistant should actively participate in the operation process, choose the appropriate trocar position according to patient's body habitus. Moreover, he should master various surgical instruments skillfully and switch instruments fluently to assist the surgeon to expose key parts during operation, and provide effective help in the operative details, so that the whole operation process can run more smoothly and the operation efficiency and quality will be greatly improved. The growth of the assistants needs constant practice and summary of experience. Meanwhile, the encouragement of the chief surgeon also plays a positive role in promoting the development of the assistants.

An excellent assistant for robotic radical gastrectomy can play an important role in the operation, especially in a initial team. In robotic gastric cancer surgery, an excellent assistant should actively participate in the operation process, choose the appropriate trocar position according to patient's body habitus. Moreover, he should master various surgical instruments skillfully and switch instruments fluently to assist the surgeon to expose key parts during operation, and provide effective help in the operative details, so that the whole operation process can run more smoothly and the operation efficiency and quality will be greatly improved. The growth of the assistants needs constant practice and summary of experience. Meanwhile, the encouragement of the chief surgeon also plays a positive role in promoting the development of the assistants.

Objective To study the mental health conditions of students majored in stomatology and dental technology in internships,and to provide evidences and guidelines for education before and during exercitation.Methods Totally 90 students majored in stomatology and 60 students majored in dental technology in internships were surveyed by the questionnaires of symptom checklist (SCL90)and perceived social support scale (PSSS).Results were analyzed by SPSS 14.0.Measurement data was analyzed using t test comparison between groups,showed as mean ± standard deviation ((x) ± s).Positive screening rate and rate between male and female were analyzed by Mann-Whitney U inspection.The inspection level is α =0.05.Results Scores of somatization,paranoia and anxiety factors among students majored in stomatology were (1.49 ± 0.56),(1.52 ± 0.43),(1.73 ± 0.58),all significantly higher than those of the national norm of youth.Positive rate of mental diseases among students majored in dental technology was 77.59％ and their scores of somatization,constraint,anxiety,psychotic factors were (1.69 ±0.55),(2.07 ±0.5),(1.68 ±0.51) and (1.54 ±0.39),all significantly higher than those of students majored in stomatology.There was no difference in the scores of rest factors between the two groups.Scores of PSSS among students majored in dental technology were significantly lower than those of students majored stomatology.Conclusions Students of different majors all suffer from psychological problems with different degrees.Therefore,education,management and social support before and during exercitation should be emphasized in the prevention of psychological diseases.

Objective To study to the effect of 1064-nm Q-switched Nd:YAG laser irradiation on the melanogenesis in a human epidermal melanocyte line PIG. Methods Cultured PIG cells were irradiated with 1064-nm Q-switched Nd:YAG laser (Medlite C6) at different energy densities for 10 times. After additional culture for various durations, cell viability was detected by MT assay, tyrosinase activity by dopa oxidation assay, mRNA and protein expressions of tyrosinase, tyrosinase related protein (TRP)-1 and TRP-2 by real-time quantitative fluorescent RT-PCR and Westen blotting respectively, Results The irradiation with Q-switched Nd:YAG laser at energy densities from 1 to 3 J/cm2 had no obvious effect on the viability of PIG cells. After irradiation with Nd:YAG laser at 1 J/cm2, PIG cells showed a significant increase in the tyrosinase activity,mRNA expressions of tyrosinase and TRP-1 compared with unirradiated cells (0.563 ± 0.014 vs 0.501 ±0.019, 1.40±0.11 vs 1.0, 1.28 ± 0.03 vs 1.0, all P＜ 0.05), but both the mRNA (0.91 ± 0.17 vs 1.0, P＞0.05) and protein expressions of TRP-2 experienced no significant changes before and after the irradiation.However, a significant decrease was noted in PIG cells irradiated with Nd:YAG laser at 3 J/cm2 in tyrosinase activity, mRNA and protein expressions of tyrosinase (0.70 ± 0.02 vs 1.0, 0.64 ± 0.05 vs 1.0, both P ＜ 0.05),TRP-1 (0.73±0.04 vs l.0, 0.86±0.17 vs l.0, both P＜0.05) andTRP-2 (0.68±0.04 vs l.0,0.69±0.11vs 1.0, both P ＜0.05) in comparison with unirradiated PIG cells. Conclusions The 1064-nm Q-switched Nd:YAG laser irradiation may affect the melanogenesis in PIG cells. With no influence on cell viability, the 1064-nm Q-switched Nd:YAG laser at 1 J/cm2 could enhance melanogenesis, while that at 3 J/cm2 could suppress melanogenesis, in PIG cells.