Objective:To investigate the clinical significance of the primary tumor size in patients with endometrial carcinoma (EC).Methods:A total of 385 patients with EC admitted to Peking University People's Hospital from January 2006 to December 2016 with complete follow up data were selected, whose tumor size data before biopsy were retrospectively studied.Results:(1) The mean diameter of the primary tumor was (3.6±1.8) cm (range: 1-15 cm). And 48 cases were 0-<2 cm, 78 cases were 2-<3 cm, 92 cases were 3-<4 cm, 73 cases were 4-<5 cm, 94 cases were ≥5 cm. The diameter of the tumor was associated with age <60 years old, premenopause, CA 125≥35 kU/L, non-parturition, poor differentiation, stage Ⅲ-Ⅳ, depth of myometrial infiltration ≥1/2, cervical interstitial involvement, adnexal metastasis and lymph node metastasis (all P<0.05), but not associated with body mass index, hypertension, diabetes mellitus, pathology, lymph-vascular space invasion (all P>0.05). (2) Among the 334 patients underwent lymphadenectomy, 45 (13.5%, 45/334) cases with lymph node metastasis were observed. Stratified analysis showed that lymph node metastasis and recurrence rate of patients with EC gradually increased with the increase of tumor size ( P<0.05). Adopting 2, 3, 4 and 5 cm as cut-off values of tumor size, there were significant differences in the rate of lymph node metastasis and recurrence among them observed ( P<0.05), except for lymph node metastasis rate and recurrence rate when the cut-off value was 2 cm ( P>0.05). (3) An receiver operating characteristic (ROC) curve analysis showed that a tumor diameter of 4.25 cm was the cut-off prognostic value to predict lymph node metastasis and recurrence of EC. Conclusions:Tumor diameter is significantly correlated with lymph node metastasis and recurrence in patients with EC. Tumor size should be considered in determining the scope of surgery and adjuvant therapy.

In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Objective:To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC).Methods:Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People′s Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed.Results:(1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA 125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H ( P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences ( P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference ( P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion:TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.

Objective: This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. Methods: Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. Results: The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p<0.001) and negative PR expression (p=0.007) were independently associated with LVSI. Both Kaplan-Meier method and univariate Cox regressions showed LVSI negative and positive cases had similar tumor-specific survival (TSS) and disease-free survival (DFS). After adjusting for the influence of adjuvant therapy and other clinicopathological factors with multivariate Cox regressions, LVSI still could not bring additional survival risk to the patients (p=0.280 and p=0.650 for TSS and DFS, respectively). This result was verified by Kaplan-Meier survival analyses after propensity score matching (p=0.234 and p=0.765 for TSS and DFS, respectively). Conclusion LVSI does not significantly compromise the survival outcome of Chinese EEC patients.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.