Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

The correlation between hemoglobin concentration and blood pressure during pregnancy in different trimesters.

Background: Maternal hemoglobin (Hb) is related to nutritional status, and it widely fluctuates during pregnancy. However, the relationship between Hb and blood pressure (BP) during pregnancy is unclear. This study aimed to estimate the associations between maternal Hb in various trimesters and its changes with BP during pregnancy.

Proteomics analysis revealed the therapeutic role of adipose-derived mesenchymal stem cells on radiation-induced colorectal fibrosis in rats.

Background: Radiation-induced colorectal fibrosis (RICF) is a chronic condition that can develop after pelvic radiation therapy for colorectal cancer. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as promising candidate for fibrosis treatment, yet the mode of action of ADSC upon RICF remains obscure. This study aimed to investigate the optimal delivery route, treatment timing, anti-fibrotic effects, and underlying mechanisms of ADSCs upon RICF.

Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years.

We present 10-year results of the phase Ⅲ FOWARC trial, which evaluated the efficacy of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with or without radiation compared with fluorouracil with radiation in patients with locally advanced rectal cancer. A total of 495 patients age 18-75 years with stage Ⅱ-Ⅲ rectal cancer were randomly assigned to three treatment arms: fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, or mFOLFOX6 alone, followed by surgery and adjuvant chemotherapy. With a median follow-up of 10 years, the 10-year disease-free survival (DFS) rates were 52.

Extramacular paracentral acute middle maculopathy-like retinal ischemia after vitrectomy for epiretinal membrane.

Purpose: To describe two cases of extramacular paracentral acute middle maculopathy (PAMM)-like retinal ischemia after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM).

Observations: Case 1 involved a 78-year-old woman with a history of hyperlipidemia and preoperative visual acuity (VA) of 20/20. Case 2 involved a 72-year-old man with a history of hypertension and hyperlipidemia, and preoperative VA of 20/32.