To evaluate the current diagnostic criteria in reporting nuclear features of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), nine Asian pathologists with expertise in thyroid reviewed virtual slides of 30 noninvasive follicular patterned thyroid lesions according to the nuclear scoring system originally proposed by an international expert and a more detailed scoring system proposed by the Asian Working Group. The interobserver agreement for nuclear grading score was generally moderate (kappa value = 0.452). The best consistency fell on the chromatin features (kappa value = 0.658–1.000). A fair to moderate interobserver agreement was demonstrated in the evaluation of nuclear elongation, nuclear overlapping, membrane irregularities and distribution of papillary thyroid carcinoma (PTC) type nuclear features. A slight agreement was rendered for the evaluation of the nuclear enlargement. Intraobserver agreement was substantial to perfect when comparing results of both scoring systems. However, both scoring systems were not able to reliably separate NIFTP from an encapsulated follicular variant PTC with minimal lymph node metastasis or BRAFV600E mutation. Although the three‐point nuclear scoring system for the diagnosis of NIFTP is widely used in Asian practice, interobserver variation was considerable. Ancillary immunohistochemical or molecular testing might be helpful in differentiating NIFTP from true PTC.

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Papillary thyroid carcinoma (PTC) is the most commonly diagnosed endocrine cancer, and those with BRAFV600E mutation have high recurrence rate and less favorable clinical behavior. Genistein having anti-carcinoma effects in various types of carcinomas as an estrogen analog, but the mechanism of Genistein in the progression of PTC remains unknown. Genistein significantly inhibits the proliferation and the invasion (P < 0.01), and the apoptosis (P < 0.001) of all tumor cell lines, which was probably due to the inducing of the arrest in G2/M phase of the cell cycle (P < 0.001). The anti-proliferation and apoptosis inducing effects are more obvious in BCPAP, IHH4 cell lines harboring BRAFV600E mutation. Genistein significantly decreased the invasion of PTC cell lines and partially reverses epithelial mesenchymal transition in PTC cell lines. Functional study indicated that small interfering RNA (siRNA) knockdown of β-catenin significantly reverses the effect of genistein on EMT at protein levels. In conclusion, for the first time, our study suggested that genistein has anticarcinoma effect for PTC patients in the range of 2.5 and 80 μg/ml in thyroid carcinoma cells, which was probably through cytoplasmic translocation of β-catenin. Further study will be needed to determine whether genistein could be used in clinical trial of high-risk PTC.

Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A GABA receptor (GABA R) subunits was upregulated in ethanol-treated mice compared with saline-treated controls. Remarkably, pretreatment of mice with GABA (1.5 mg kg body weight, intraperitoneal injection [i.p.]) or with the GABA R agonist muscimol (1.2 mg kg body weight, i.p.) protected the liver against ethanol toxicity and improved liver function, whereas pretreatment of mice with the GABA R antagonist bicuculline (2.0 mg kg body weight, i.p.) worsened the liver function. Further analyses suggest that GABA R-mediated signaling protects the liver from ethanol injury by, at least partially, inhibiting the IRE1α-ASK1-JNK pro-apoptotic pathway in hepatocytes in the process of ethanol-induced endoplasmic reticulum stress response.