Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration.

Asherman's syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman's syndrome.

Relationship between serum TGF- ß 1, MMP-9 and IL-1ß and pathological features and prognosis in breast cancer.

To investigate the levels of serum transforming growth factor-ß 1 (TGF-ß1), Matrix metalloproteinase-9 (MMP-9) and Interleukin-1 ß (IL-1 ß) in breast cancer (BC), and analyzing their relationship with pathological features and prognosis. Retrospective analysis of 86 subjects with BC (BC subgroup) and another 50 healthy subjects (control subgroup) during the same period were included. The clinical data were collected. In this research, in BC subgroup, The levels of serum TGF- ß 1, MMP-9 and IL-1 ß were significantly higher than those in control subgroup. The levels of TGF- ß 1 and MMP-9 in serum of BC subjects was correlated with clinical stage, histological grade, lymph node metastasis and molecular classification, but not with age, tumor size and menopausal status. The level of serum IL-1 ß was related to tumor size, clinical stage, histological grade and lymph node metastasis. Multivariate Logistic regression analysis showed that the high level of serum TGF- ß1 and MMP-9 was independent risk factors for BC. High level of serum IL-1 ß was not an independent risk factor for BC. The 3-year disease-free survival rate in high TGF- ß1 subgroup and high MMP-9 subgroup was significantly lower than that in low TGF- ß 1 subgroup and low MMP- 9 subgroup. To conclude, serum TGF- ß 1, MMP-9 and IL-1ß are highly expressed in BC, and the subjects with elevated serum levels of TGF- ß 1 and MMP-9 suggests poor prognosis.

Atorvastatin inhibits proliferation and promotes apoptosis of colon cancer cells via COX-2/PGE2/ß-Catenin Pathway.

PURPOSE: To explore the effects of atorvastatin (ATST) on the proliferation and apoptosis of colon cancer cells through the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/ß-catenin pathway. METHODS: HCT116 cells were cultured and transfected, and they were treated with ATST at different concentrations for different time. The association between the expressions of COX-2 and PGE2 and the survival time of patients with colon cancer was analyzed via Kaplan-Meier survival analysis. Then the protein expressions of COX-2, ß-catenin and apoptosis-related molecules in HCT116 cells were determined using Western blotting, and the proliferation of HCT116 cells was detected via cell counting kit-8 (CCK-8) assay. RESULTS: There was a significant difference in the survival rate between HCT116 cells treated with 30 µM ATST and those treated with 0 µM ATST. The survival time was obviously longer in patients with low expressions of COX-2 and PGE2 than that those with high expressions of COX-2 and PGE2. Low expressions of COX-2 and PGE2 in colon cancer tissues indicate a longer survival time. Moreover, a positive correlation was found between HCT116 cell density and COX-2 level, HCT116 cell density and PGE2 level, and COX-2 and PGE2 levels. ATST could down-regulate COX-2 and ß-catenin, and knocking down COX-2 could lower ß-catenin. After treatment with ATST and ATST + anti-COX-2, the activity of cleaved caspase-9, caspase-3 and PARP was remarkably enhanced, suggesting that ATST and ATST + anti-COX-2 can promote apoptosis of HCT116 cells. It was found that ATST and ATST + anti-COX-2 could also inhibit the proliferation of HCT116 cells.

Prediction of postoperative hematoma occurrence after ultrasound-guided vacuum-assisted breast biopsy in minimally invasive surgery for percutaneous removal of benign breast lesions.

BACKGROUND: The exact factors and mechanisms involved in the development of hematoma after breast ultrasound (US)-guided vacuum-assisted biopsy (VAB) are not clear. This study aimed to analyze the occurrence, prognosis, and risk factors of hematoma after US-guided VAB for the removal of benign breast lesions. METHODS: This was a retrospective study of consecutive female patients with breast lesions (BI-RADS 3/4a/4b and confirmed as benign by core needle biopsy) removed by percutaneous excisional biopsy by US-guided VAB at the Beijing Chaoyang Hospital from April 2016 to December 2018. Univariable analyses were conducted to identify the factors associated with hematoma (age, nodule size, laterality, nodule location, number of nodules, BI-RADS classification of ultrasound, pathology, breast shape, menstrual period, efficacy time of bandage, and hemostatic agents). Multivariable analysis was performed to identify the factors independently associated with hematoma. RESULTS: A total of 293 patients (343 breast lesions) were included. Lesion removal was successful in all cases. Hematomas ≥1 cm were found in 39 patients. Finally, 38 (97.4%) hematomas were absorbed completely within 6 months. The multivariable logistic regression analysis revealed that lesion size (P<0.001; OR: 5.775; 95% CI: 2.752-12.121), number of lesions (P=0.011; OR: 3.205, 95% CI: 1.311-7.834), and the efficacy time of bandage 12-24 h (P=0.003; OR: 5.257, 95% CI: 1.792-15.421) were independently associated with hematoma occurrence after US-guided VAB excision of breast lesions. A lesion size cut-off of 23.4 mm (AUC 0.764, 95% CI: 0.692-0.837; 59.0% sensitivity; 80.3% specificity; 77.5% accuracy; P<0.001) could predict hematoma occurrence. CONCLUSIONS: US-guided excisional VAB can effectively remove benign breast lesions. The factors independently associated with postoperative hematoma are lesion size, lesion number, and effective postoperative compression time of bandage.

Measurement of serum intact parathyroid hormone concentration 1 day after total thyroidectomy to assess risk of permanent hypoparathyroidism.

OBJECTIVE: This study was performed to assess the clinical value of measuring the intact parathyroid hormone (iPTH) concentration 1 day after total thyroidectomy to estimate the occurrence of permanent hypoparathyroidism (pHPP). METHODS: Data of 546 patients who underwent total thyroidectomy from February 2008 to December 2018 were retrospectively analyzed. Calcium and iPTH concentrations were collected preoperatively and at 1 day and 6 months postoperatively. Logistic regression was used to analyze the correlation between clinical indexes and postoperative pHPP. RESULTS: Of the 546 patients, 22 (4.03%) developed pHPP. Multivariate analysis showed that the iPTH and serum calcium concentrations measured 1 day after surgery were independent predictors of the risk of pHPP. An iPTH concentration of 5.51 pg/mL measured 1 day postoperatively was used as the cut-off value, and the area under the curve was 0.956. The risk of pHPP was identified with a sensitivity of 100%, specificity of 85.1%, positive predictive value of 22%, and negative predictive value of 100%. CONCLUSIONS: The iPTH concentration measured 1 day after total thyroidectomy is closely related to the occurrence of pHPP postoperatively and is an independent predictive risk factor. The postoperative iPTH concentration can be helpful in identifying patients at risk for developing pHPP.

Positive non-sentinel axillary lymph nodes in breast cancer with 1-2 sentinel lymph node metastases.

Recent clinical trials have shown that sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) can offer excellent regional control if there is sentinel lymph nodes (SLN) metastases to 1-2 nodes. This study aimed to explore the predictive factors for non-sentinel lymph node (NSLN) metastasis in breast cancer patients with 1-2 positive SLNs.Patients with breast cancer and 1-2 positive SLN admitted between March 2009 and March 2017 and who underwent ALND after SLN biopsy (SLNB) at Beijing Chaoyang Hospital were analyzed retrospectively. Factors influencing the status of NSLN were studied by univariate and multivariate analysis.Of 1125 patients, 147 patients had SLN metastasis (13.1%) and 119 patients (81.0%) had 1-2 positive SLNs. Among them, 42 patients (35.3%) had NSLN metastasis. The invasive tumor size (P <.001), histological grade (P =.011), lymphovascular invasion (LVI) (P =.006), and over-expression of HER2 (P =.025) significantly correlated with non-SLN metastasis by univariate analysis. LVI (LVI) (P =.007; OR: 4.130; 95% confidence interval [CI]: 1.465-11.641), invasive tumor size (P <.001; OR: 7.176; 95% CI: 2.710-19.002), and HER2 over-expression (P =.006; OR: 5.489; 95% CI: 1.635-18.428) were independently associated with NSLN metastasis by the Logistic regression model. The ROC analysis identified a cut-off point of 26 mm of tumor size (area under the receiver operating characteristic [ROC] curve [AUC] 0.712, CI: 0.614-0.811) was useful for dividing patients with positive SLN (1-2 nodes) into non-SLN-positive and non-SLN-negative groups.For 1-2 positive SLNs of breast cancer, LVI, large invasive tumor size, and HER2 over-expression are independent factors affecting NSLN metastases.

Evaluation of clinical significance and risk factors of incidental parathyroidectomy due to thyroidectomy: A single-center retrospective clinical study.

We assessed the clinical significance and risk factors of incidental parathyroidectomy during total thyroidectomy with or without central neck dissection or subtotal thyroidectomy.Retrospective analysis of clinical and pathological features of 548 consecutive thyroidectomy cases was compared by grouping into inadvertent resection (IR, n = 86) with IR of parathyroid glands, non-IR (n = 462) without, and then into postoperative hypoparathyroidism (PH, n = 140) with PH and non-PH (n = 408) without.Two hundred ninety-eight patients had total thyroidectomy and 250 had subtotal thyroidectomy. IR had higher malignant disease (P < .001), total thyroidectomy (P = .016), T3 and T4 classification (P = .005), central neck dissection (P < .001), recurrent laryngeal nerve palsy (P = .003), postoperative transient hypoparathyroidism (P < .001), duration of disease prior to thyroidectomy (P < .001), and weight of excised thyroid tissue (P < .001) than non-IR.Preoperative diagnosis of malignant disease, duration of disease prior to thyroidectomy, and central neck dissection were independent risk factors for incidental parathyroidectomy. Preoperative diagnosis of malignant disease, central neck dissection, duration of disease prior to thyroidectomy, weight of excised thyroid tissue, and incidental parathyroidectomy were correlated with PH.