A radio-pathologic integrated model for prediction of lymph node metastasis stage in patients with gastric cancer.

BACKGROUND: Accurate prediction of lymph node metastasis stage (LNMs) facilitates precision therapy for gastric cancer. We aimed to develop and validate a deep learning-based radio-pathologic model to predict the LNM stage in patients with gastric cancer by integrating CT images and histopathological whole-slide images (WSIs). METHODS: A total of 252 patients were enrolled and randomly divided into a training set (n = 202) and a testing set (n = 50). Both pretreatment contrast-enhanced abdominal CT and WSI of biopsy specimens were collected for each patient. The deep radiologic and pathologic features were extracted from CT and WSI using ResNet-50 and Vision Transformer (ViT) network, respectively. By fusing both radiologic and pathologic features, a radio-pathologic integrated model was constructed to predict the five LNM stages. For comparison, four single-modality models using CT images or WSIs were also constructed, respectively. All models were trained on the training set and validated on the testing set. RESULTS: The radio-pathologic integrated mode achieved an overall accuracy of 84.0% and a kappa coefficient of 0.795 on the testing set. The areas under the curves (AUCs) of the integrated model in predicting the five LNM stages were 0.978 (95% Confidence Interval (CI 0.917-1.000), 0.946 (95% CI 0.867-1.000), 0.890 (95% CI 0.718-1.000), 0.971 (95% CI 0.920-1.000), and 0.982 (95% CI 0.911-1.000), respectively. Moreover, the integrated model achieved an AUC of 0.978 (95% CI 0.912-1.000) in predicting the binary status of nodal metastasis. CONCLUSION: Our study suggests that radio-pathologic integrated model that combined both macroscale radiologic image and microscale pathologic image can better predict lymph node metastasis stage in patients with gastric cancer.

Clinical outcomes of multifocal papillary thyroid cancer: A systematic review and meta-analysis.

Objective: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a steadily increasing incidence. Researches have reported that tumor multifocality occurs in an extensive number of cases. Nevertheless, the clinical characteristics and prognostic value remained controversial. This study was performed to investigate the relationship between multifocal PTC and adverse clinicopathologic features and the prognosis. Methods: A systematic review and meta-analysis were conducted based on three electronic databases up to December 31, 2021. Parameters of interest included five clinical features (extrathyroidal extension, lymphovascular invasion, central lymph node metastasis, lateral lymph node metastasis, distant metastasis) and were pooled into risk ratios (RRs). Time-to-event data (recurrence-free survival and all-cause mortality) were evaluated using hazard ratios (HRs). Publication bias was examined using funnel plots and Egger's test. Results: A total of 23 articles were included according to the inclusion criteria; all of the studies were retrospective cohorts. In comparison with unifocality, multifocality showed an increased risk of extrathyroidal extension (RR 1.38, 95% CI 1.25-1.53), lymphovascular invasion (RR 1.27, 95% CI 1.04-1.55), central lymph node metastasis (RR 1.21, 95% CI 1.12-1.30), lateral lymph node metastasis (RR 1.86, 95% CI 1.62-2.14), and distant metastasis (RR 1.35, 95% CI 1.03-1.76). Multifocal patients were predisposed to postoperative recurrence (HR 1.76, 95% CI 1.50-2.07). The rate of all-cause mortality did not reach a statistical difference. Level of Evidence: 2. Conclusion: Multifocal PTC is more aggressive in contrast to unifocal PTC and is accompanied by an increased risk of recurrence. They were usually diagnosed in higher grades and stages. To achieve the maximal benefit, we recommend personalized therapy and close follow-up for multifocal PTC patients. Further prospective studies will clarify the best-fitted treatment plans.

miR-25 Regulates Gastric Cancer Cell Growth and Apoptosis by Targeting EGR2.

Gastric cancer is one of the most common malignancies harmful to human health. The search for effective drugs or gene therapy has aroused the attention of scientists. So far, microRNAs, as small non-coding RNAs, have the potential to be therapeutic targets for cancer. Herein, we found a highly expressed miR-25 in gastric cancer cell. However, the function of miR-25 for gastric cancer cell growth and apoptosis was unknown. Functionally, we used RT-qPCR, western blot, CCK-8, and flow cytometry to detect gastric cancer cell growth and apoptosis. The results indicated that miR-25 promoted gastric cancer cell growth and inhibited their apoptosis. Mechanistically, we found that a gene EGR2 was a potential target gene of miR-25. Further dual-luciferase results supported this prediction. Moreover, knockdown of EGR2 promoted gastric cancer cell growth and inhibited their apoptosis by flow cytometry detection. Altogether, these findings revealed miR-25 as a regulator of gastric cancer cell growth and apoptosis through targeting EGR2.

Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy, and the incidence is increasing very fast. Surgical resection and radioactive iodine ablation are major therapeutic methods, however, around 10% of differentiated thyroid cancer and all anaplastic thyroid carcinoma (ATC) are failed. Comprehensive understanding the molecular mechanisms may provide new therapeutic strategies for thyroid cancer. Even though genetic heterogeneity is rigorously studied in various cancers, epigenetic heterogeneity in human cancer remains unclear. METHODS: A total of 405 surgical resected thyroid cancer samples were employed (three spatially isolated specimens were obtained from different regions of the same tumor). Twenty-four genes were selected for methylation screening, and frequently methylated genes in thyroid cancer were used for further validation. Methylation specific PCR (MSP) approach was employed to detect the gene promoter region methylation. RESULTS: Five genes (AP2, CDH1, DACT2, HIN1, and RASSF1A) are found frequently methylated (>30%) in thyroid cancer. The five genes panel is used for further epigenetic heterogeneity analysis. AP2 methylation is associated with gender (P < 0.05), DACT2 methylation is associated with age, gender and tumor size (all P < 0.05), HIN1 methylation is associated to tumor size (P < 0.05) and extra-thyroidal extension (P < 0.01). RASSF1A methylation is associated with lymph node metastasis (P < 0.01). For heterogeneity analysis, AP2 methylation heterogeneity is associated with tumor size (P < 0.01), CDH1 methylation heterogeneity is associated with lymph node metastasis (P < 0.05), DACT2 methylation heterogeneity is associated with tumor size (P < 0.01), HIN1 methylation heterogeneity is associated with tumor size and extra-thyroidal extension (all P < 0.01). The multivariable analysis suggested that the risk of lymph node metastasis is 2.5 times in CDH1 heterogeneous methylation group (OR = 2.512, 95% CI 1.135, 5.557, P = 0.023). The risk of extra-thyroidal extension is almost 3 times in HIN1 heterogeneous methylation group (OR = 2.607, 95% CI 1.138, 5.971, P = 0.023). CONCLUSION: Five of twenty-four genes were found frequently methylated in human thyroid cancer. Based on 5 genes panel analysis, epigenetic heterogeneity is an universal event. Epigenetic heterogeneity is associated with cancer development and progression.

Kinetic Resolution of 2,2-Disubstituted Dihydroquinolines through Chiral Phosphoric Acid-Catalyzed C6-Selective Asymmetric Halogenations.

A novel kinetic resolution of 2,2-disubstituted dihydroquinolines was achieved by regioselective asymmetric halogenations enabled by chiral phosphoric acid catalysis. A series of dihydroquinolines bearing 2,2-disubstitutions were well-tolerated in these reactions, generating both the recovered dihydroquinolines and C-6-brominated products with high enantioselectivities, with s-factors up to 149. In addition, this kinetic resolution protocol is also applicable for 2,2-disubstituted tetrahydroquinoline and asymmetric iodonation reaction.

Asymmetric Synthesis of Hydroquinolines with α,α-Disubstitution through Organocatalyzed Kinetic Resolution.

The first kinetic resolution of hydroquinoline derivatives with α,α-disubstitution has been achieved through asymmetric remote aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. Mechanistic studies suggest a monomeric catalyst pathway proceeding through rate- and enantio-determining electrophilic attack promoted by a network of attractive non-covalent interactions between the substrate and catalyst. Facile subsequent removal and transformations of the newly introduced hydrazine moiety enable these protocols to serve as powerful tools for asymmetric synthesis of N-heterocycles with α,α-disubstitution.

Rheological behaviors of microbial polysaccharides with different substituents in aqueous solutions: Effects of concentration, temperature, inorganic salt and surfactant.

Rheological behaviors of microbial polysaccharides with different substituents in aqueous solutions have been systematically investigated. Both the saccharide side chains and acetyl substituents improve the gelation of welan gum (WG), diutan gum (DG) and gellan gum (GG) in pure water at 25 °C. For the polysaccharides with saccharide side chains (WG and DG), the relationship between the apparent viscosity and concentration conforms to the linear equation, while that of the polysaccharide with acetyl (GG) is exponential. More importantly, the roles of substituents on the stability of the molecular conformation of polysaccharides are significantly depended on the surrounding environment. Disaccharide side chains promote the stability of helical conformation and gel aggregates of GG at high temperature (85 °C) or in the presence of inorganic salts with the ionic strength of 2.0 mol L-1. The stability of gel structure containing acetyl (GG) shows higher temperature/salt sensitivity. Additionally, deacylated gellan gum (GG(d)) solutions transform into hydrogels in the presence of dodecyltrimethylammonium bromide (DTAB). This study will help to obtain a better understanding on the rheological properties of polysaccharides with respect to the conformation and applications.