Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.

Research on Cognition and Training Needs of Sex Education during Pregnancy among Obstetricians and Obstetric Nurses in Guangdong Province Based on Mixed Research Perspective.

Objective: The purpose of this study was to understand the current status and existing responses of obstetricians and obstetric nurses in Guangdong Province regarding sex education during pregnancy and to understand their acceptance of sex education during pregnancy and the knowledge and information they would like to obtain in sex education courses. Methods: A phenomenological research method was used to conduct in-depth interviews with 12 obstetricians and obstetric nurses in a tertiary hospital in Guangdong Province to understand their perceptions and attitudes toward providing sex education to pregnant women. A self-designed questionnaire was used to survey 462 obstetricians and obstetric nurses in Guangdong Province to understand their needs for sex education. Results: Three themes were summarized: insufficient awareness of sex education during pregnancy; negative attitudes of obstetricians and obstetric nurses toward sex education during pregnancy; and the need for a long-term process for the development and popularization of sex education during pregnancy. We obtained the required scores of obstetricians and obstetric nurses on 11 aspects of sex education during pregnancy with a coefficient of variation ≤25%. Conclusion: There is an urgent need to improve the awareness and related competencies of obstetricians and obstetric nurses about sex education during pregnancy, and the purpose and content of sex education courses should be in line with the clinical reality.

Bone marrow-derived mesenchymal stem cells expressing BMP2 suppress glioma stem cell growth and stemness through Bcl-2/Bax signaling.

Objectives: To find an effective molecule that controls glioma stem cell (GSC) proliferation and differentiation for the development of future therapeutic interventions against glioblastoma. Material and Methods: Bone marrow-derived mesenchymal stem cells (BMSCs) were infected with a lentiviral vector to express BMP2. Cell viability, cell counting, and tumor sphere formation assays, as well as flow cytometry, immunofluorescence staining, and Western blotting were used to investigate the effects of BMSC-BMP2 on GSCs. Results: The results of flow cytometry and the CKK-8 assay showed that BMSC-BMP2 induced GSC apoptosis while inhibiting proliferation. BMSC-BMP2 decreased GSC neurosphere formation and neurospheres' transverse and vertical diameter. Meanwhile, BMSC-BMP2 downregulated GSC Nanog and OCT4 expression levels, suggesting stemness inhibition. Western blotting showed that BMSC-BMP2 increased Bax protein expression and significantly decreased Bcl-2 protein expression. Accordingly, the Bcl-2/Bax ratio increased. Conclusion: BMSC-BMP2 could effectively inhibit GSC proliferation, induce GSC apoptosis, and decrease GSC stemness, thereby providing a novel strategy for treating malignant glioma.

Papillary Solitary Fibrous Tumor/Hemangiopericytoma: An Uncommon Morphological Form With NAB2-STAT6 Gene Fusion.

Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by "staghorn" blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56-165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.

[Investigation on snails Achatina fulica and Pomacea canaliculata infected with Angiostrongylus cantonensis in Panyu region of Guangzhou City].

OBJECTIVE: To understand the natural infection status of Angiostrongylus cantonensis in snails Achatina fulica and Pomacea canaliculata from Panyu region of Guangzhou City. METHODS: The snails Achatina fulica and Pomacea canaliculata captured from the field were digested with the artificial stomach fluid. The third-stage larvae of A. cantonensis were examined and counted under a microscope. The collected third-stage larvae were used to infect SD rats. RESULTS: A total of 367 Achatina fulica and 357 Pomacea canaliculata were examined. The infection rate of A. cantonensis in Achatina fulica was 22.62%, with a mean intensity of 57.00 larvae per positive snail. The infection rate of A. cantonensis in Pomacea canaliculata was 3.08%, with a mean intensity of 1.64 larvae per positive snail. The infection rates of A. cantonensis in Achatina fulica from Dagang, Shiqi, Hualong, and Lanhe towns and Nansha District, were 13.33%, 15.00%, 20.93%, 73.68% and 8.41%, respectively. Those in Pomacea canaliculata were 5.88%, 2.88%, 1.89%, 0% and 3.96%, respectively. CONCLUSIONS: A. cantonensis infection exists in Achatina fulica and Pomacea canaliculata from Panyu region of Guangzhou City, and the infection in Achatina fulica is more serious than that in Pomacea canaliculata. The infection rates of the snails among five sites are different.