Background: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. Methods: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. Results: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. Conclusions: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.

Background: When determining adjuvant treatment for endometrial cancer, the decision typically relies on factors such as cancer stage, histologic grade, subtype, and a few histopathologic markers. The Cancer Genome Atlas revealed molecular subtyping of endometrial cancer, which can provide more accurate prognostic information and guide personalized treatment plans.Objective: To summarize the expression and molecular basis of the main biomarkers of endometrial cancer.Search Strategy: PubMed was searched from January 2000 to March 2023.Selection Criteria: Studies evaluating molecular subtypes of endometrial cancer and implications for adjuvant treatment strategies.Data Collection and Analysis: Three authors independently performed a comprehensive literature search, collected and extracted data, and assessed the methodological quality of the included studies.Main Results: We summarized the molecular subtyping of endometrial cancer, including mismatch repair deficient, high microsatellite instability, polymerase epsilon (POLE) exonuclease domain mutated, TP53 gene mutation, and non‐specific molecular spectrum. We also summarized planned and ongoing clinical trials and common therapy methods in endometrial cancer. POLE mutated endometrial cancer consistently exhibits favorable patient outcomes, regardless of adjuvant therapy. Genomic similarities between p53 abnormality endometrial cancer and high‐grade serous ovarian cancer suggested possible overlapping treatment strategies. High levels of immune checkpoint molecules, such as programmed cell death 1 and programmed cell death 1 ligand 1 can counterbalance mismatch repair deficient endometrial cancer immune phenotype. Hormonal treatment is an appealing option for high‐risk non‐specific molecular spectrum endometrial cancers, which are typically endometrioid and hormone receptor positive. Combining clinical and pathologic characteristics to guide treatment decisions for patients, including concurrent radiochemotherapy, chemotherapy, inhibitor therapy, endocrine therapy, and immunotherapy, might improve the management of endometrial cancer and provide more effective treatment options for patients.Conclusions: We have characterized the molecular subtypes of endometrial cancer and discuss their value in terms of a patient‐tailored therapy in order to prevent significant under‐ or overtreatment.

Objectives. The standardized residency training (SRT) program in China is an important link for continuing education and clinical work training for graduate students. The purpose of our study was to enable educators to maintain the effectiveness of hysteroscopy teaching techniques and make the standardized residency training students well experienced in surgery, thus demonstrating that higher efficiency of teaching can lead to better proficiency for surgery. Methods. We generated resident-as-teacher teaching round and tutor guided hysteroscopic surgery as well as a questionnaire based on the mastery degree of the basic theoretical knowledge and operational skills of hysteroscopy among seven junior residents and five senior residents of the Obstetrics and Gynecology Department, including four attending gynecologic surgeons of a hysteroscopy teaching program. Results. Senior residents felt confident to teach, while junior residents learned effectively through the teaching round. There were statistically significant differences in the whole operation time and the volume of distension fluid used between junior and senior residents (p<0.05). Conclusions. This study acknowledges the need for new approaches to medical education for better characterization of the link between the use of teaching rounds through problem-based learning (PBL) discussion dominated by the residents themselves and overall surgical skills of teaching and learning.

VPS4 series proteins play a crucial role in the endosomal sorting complexes required for the transport (ESCRT) pathway, which is responsible for sorting and trafficking cellular proteins and is involved in various cellular processes, including cytokinesis, membrane repair, and viral budding. VPS4 proteins are ATPases that mediate the final steps of membrane fission and protein sorting as part of the ESCRT machinery. They disassemble ESCRT-III filaments, which are vital for forming multivesicular bodies (MVBs) and the release of intraluminal vesicles (ILVs), ultimately leading to the sorting and degradation of various cellular proteins, including those involved in cancer development and progression. Recent studies have shown a potential relationship between VPS4 series proteins and cancer. Evidence suggests that these proteins may have crucial roles in cancer development and progression. Several experiments have explored the association between VPS4 and different types of cancer, including gastrointestinal and reproductive system tumors, providing insight into the underlying mechanisms. Understanding the structure and function of VPS4 series proteins is critical in assessing their potential role in cancer. The evidence supporting the involvement of VPS4 series proteins in cancer provides a promising avenue for future research and therapeutic development. However, further researches are necessary to fully understand the mechanisms underlying the relationship between VPS4 series proteins and cancer and to develop effective strategies for targeting these proteins in cancer therapy. This article aims to review the structures and functions of VPS4 series proteins and the previous experiments to analyze the relationship between VPS4 series proteins and cancer.

Purpose: The study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body ¹⁸F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC). Materials and methods: A total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters—standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)—to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction. Results: Our study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression. Conclusion: The present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC. Graphic

Background: Few previous studies have introduced general techniques to overcome the “chopstick effect” in laparoendoscopic single-site surgery (LESS). We aim to investigate and highlight the key ergonomic methodologies for gynaecologic LESS based on the surgeon’s hands-on performance. Methods: The first author surgeon A reviewed and analyzed the LESS procedures performed by herself and how she taught surgeon B from January 2021 to April 2022. The procedures were classified based on technical difficulty and learning periods, and the hands-on technical skills of LESS module were evaluated. Results: Surgeon A conducted 580 LESS procedures, which were divided into the novice (n = 48) and intermediate (n = 33) periods, and the remaining cases were included in the routine period. We formed a special ergonomic LESS operating methodology: Maintain good LESS laparoscopic spatial sensation, keep hand-eye coordination, well cooperation between the main surgeon and the assistant; Experienced multiport laparoscopy surgery (MPS) skills, improve basic LESS technique: grasp, lift, transfer, place, blunt separating, coagulation and cutting. Coordination location, orientation, movements, and flexion or extension of shoulders, arms, elbow, wrist and finger joints; Maintain strength, tension and ambidexterity postures with joint and muscular efforts to control instruments. Surgeon B learned the above experiences by performing 39 LESS procedures under the guidance of surgeon A. Conclusion: This educational research sheds light on the common challenges faced in LESS and presents the importance of ergonomic hands-on performance skills in improving surgical outcomes, which could serve as a guide for future training and education in LESS.