New vision of HookEfficientNet deep neural network: Intelligent histopathological recognition system of non-small cell lung cancer.

BACKGROUND: Efficient and precise diagnosis of non-small cell lung cancer (NSCLC) is quite critical for subsequent targeted therapy and immunotherapy. Since the advent of whole slide images (WSIs), the transition from traditional histopathology to digital pathology has aroused the application of convolutional neural networks (CNNs) in histopathological recognition and diagnosis. HookNet can make full use of macroscopic and microscopic information for pathological diagnosis, but it cannot integrate other excellent CNN structures. The new version of HookEfficientNet is based on a combination of HookNet structure and EfficientNet that performs well in the recognition of general objects. Here, a high-precision artificial intelligence-guided histopathological recognition system was established by HookEfficientNet to provide a basis for the intelligent differential diagnosis of NSCLC. METHODS: A total of 216 WSIs of lung adenocarcinoma (LUAD) and 192 WSIs of lung squamous cell carcinoma (LUSC) were recruited from the First Affiliated Hospital of Zhengzhou University. Deep learning methods based on HookEfficientNet, HookNet and EfficientNet B4-B6 were developed and compared with each other using area under the curve (AUC) and the Youden index. Temperature scaling was used to calibrate the heatmap and highlight the cancer region of interest. Four pathologists of different levels blindly reviewed 108 WSIs of LUAD and LUSC, and the diagnostic results were compared with the various deep learning models. RESULTS: The HookEfficientNet model outperformed HookNet and EfficientNet B4-B6. After temperature scaling, the HookEfficientNet model achieved AUCs of 0.973, 0.980, and 0.989 and Youden index values of 0.863, 0.899, and 0.922 for LUAD, LUSC and normal lung tissue, respectively, in the testing set. The accuracy of the model was better than the average accuracy from experienced pathologists, and the model was superior to pathologists in the diagnosis of LUSC. CONCLUSIONS: HookEfficientNet can effectively recognize LUAD and LUSC with performance superior to that of senior pathologists, especially for LUSC. The model has great potential to facilitate the application of deep learning-assisted histopathological diagnosis for LUAD and LUSC in the future.

Antioxidant and neuroprotective activities of Mogami-benibana (safflower, Carthamus tinctorius Linne).

Free radical scavenging activity of the extracts of petals (bud, early stage, full blooming and ending stage), leaf, stem, root and seeds of Mogami-benibana (safflower, Carthamus tinctorius Linne), the contents of the major active components of carthamin and polyphenols, and neuroprotective effect of the petal extracts and carthamin in the brain of mice and rats were examined. Water extracts of Mogami-benibana petals scavenged superoxide, hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and singlet oxygen. The scavenging activities of the extract of safflower petals with various colors showed the order of orange, yellow and white from high to low. This order is consistent with the contents of carthamin, which is a pigment of orange color and is found highest in orange petals and lowest in white petals. There was also a relationship between DPPH radical scavenging activity and carthamin content in the petal extracts of safflower. The neuroprotective effects were examined in cellular and animal models. Mogami-benibana petal extract inhibited glutamate-induced C6 glia cell death, significantly decreased the formation of malondialdehyde in mouse cerebrum, and inhibited the increase in thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebral cortex of rats subjected to an injection of FeCl(3) solution into the sensory motor cortex. Carthamin showed similar effects in inhibiting 8-OHdG by the petal extract in rats. These results suggest that the petal extract of Mogami-benibana has free radical scavenging activity and neuroprotective effect and carthamin is one of the major active components.

Effect of the rhizomes of Atractylodes lancea and its constituents on the delay of gastric emptying.

The effect of rhizomes of Atractylodes lancea on gastric disorders, in particular, the delay in gastric emptying induced by N(G)-nitro-L-arginine in rats, was investigated. Intragastric treatment with an aqueous extract (250 mg/kg) and its lipophilic fractions (4 mg/kg) significantly improved delayed gastric emptying. The major constituents of the lipophilic fraction were two sesquiterpens, hinesol and beta-eudesmol, and four known polyacetylenic compounds, atractylodin, atractylodinol, acetylatractylodinol and 4,6,12-tetradecatriene-8,10-diyne-1,3,14-triol. The activity was found in the four polyacetylenic compounds at a similar potency, but not in the two sesquiterpens. To clarify the effect of the four polyacetylenic compounds in this extract, we attempted to evaluate the activity of atractylodin, as representative, at a dose of 0.2 mg/kg based on the total amounts (0.2 mg/250 mg aqueous extract) of the four polyacetylenic compounds. In addition, atractylodin improved the delay in gastric emptying at between 0.1 and 0.3 mg/kg in a dose-dependent manner. These results suggest that the aqueous extract improved the delayed gastric emptying, and polyacetylenic compounds contributed to its activity.

Intestinal anastomosis surgery with no septic shock primes for a dysregulatory response to a second stimulus.

BACKGROUND: Major surgery is believed to contribute to immune dysregulation and high susceptibility to microbes. Recently, the inflammatory "two-hit" model has been accepted to elucidate development of multiple organ failure in surgical patients. Our purpose was to examine whether intestinal surgery, which causes a minor insult with no septic shock, may modify the immune response to exogenous LPS as a second stimulus. MATERIALS AND METHODS: Using a rat intestinal transection and anastomosis surgery model, we sequentially examined blood cell counts, body temperatures, and plasma cytokines. Rats were administered with LPS intravenously or intratracheally various days after surgery. Phagocytic activity and TNFalpha production in bronchoalveolar lavage (BAL) cells, plasma cytokines, and survival rates were evaluated. RESULTS: The surgery itself caused no severe shock or circulating cytokine elevation, whereas the number of granulocytes in the blood was significantly elevated after surgery. LPS-induced elevation of circulating IFNgamma attenuated 3 days after surgery. In contrast, IL-10 was enhanced 3-10 days after surgery. Hyporesponsiveness of BAL cells to LPS was observed 3 days after surgery but not the next day after surgery. However, rats intratracheally exposed to LPS 10-13 days after surgery exhibited higher mortality. CONCLUSIONS: Although our surgical procedure was not supposed to be a severe insult, it sufficiently primed rats for an altered response to a second stimulus (endotoxin), which included enhanced mortality. This study provided an improved understanding of pathophysiological changes following surgery and described a useful model for developing preventive and therapeutic strategies for complications after surgery.

Effects of rikkunshi-to, a traditional Japanese medicine, on the delay of gastric emptying induced by N(G)-nitro-L-arginine.

We evaluated the effects of Rikkunshi-to and several of its ingredients on the delay of gastric emptying induced by a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine (L-NNA). After oral administration of L-NNA to rats, the gastric emptying rate at 24 h was decreased from 82.8 +/- 2.4% to 53.3 +/- 5.7%. The decrease of the gastric emptying rate induced by L-NNA treatment was markedly ameliorated by administration of Rikkunshi-to (250 and 500 mg/kg, p.o.) in a dose-dependent manner. To identify the active ingredient of Rikkunshi-to, the components were separated according to polarity, and the effects of the respective fractions on gastric emptying were evaluated. Significant efficacy was found in the water and methanol fractions, but not in the 50% aqueous-methanol fraction. Furthermore, hesperidin (1 - 4.29 mg/kg, p.o.) contained in the methanol fraction and L-arginine (4.5 mg/kg, p.o.) contained in the water fraction ameliorated the decrease in the gastric emptying rate induced by L-NNA treatment. These results suggest that Rikkunshi-to ameliorated abnormalities of NO-mediated gastric functions such as delayed gastric emptying, and hesperidin and L-arginine were identified as two of the active ingredients contributing to the ability of Rikkunshi-to to facilitate gastric emptying.

Pharmacological evaluation of Shokyo and Kankyo (1).

Zingiberis Rhizoma (Shokyo, [Japanese characters: see text]) showed significant ameliorative effect on the BaCl2-induced delay of gastric emptying in rat. Bioassay-guided fractionation of the aqueous extract of Shokyo resulted in isolation of 6-gingesulfonic acid (1) and shogasulfonic acid A (3). These compounds significantly improved the delay of gastric emptying on both BaCl2-induced and N(G)-nitro-L-arginine (L-NNA)-induced model in rat. Zingiberis Siccatum Rhizoma (Kankyo, [Japanese characters: see text]) had significant efficacy against castor oil-induced diarrhea. In addition, Kankyo showed the activity increasing intestinal blood flow in normal rat.

Pharmacological characteristics of Ryokan-kyomi-shinge-nin-to, an antiallergic Kampo medicine.

The pharmacological characteristics of Ryokan-kyomi-shinge-nin-to (RKS), a traditional oriental herbal (Kampo) medicine which has been used for the treatment of allergic asthma and rhinitis, were investigated. The number of sneezes by actively sensitized mice after a topical antigen challenge was significantly reduced by pretreatment with RKS (300 and 1000 mg/kg, p.o.). Although RKS did not inhibit the antigen-induced histamine release from rat peritoneal exudate cells (PEC), it significantly inhibited an increase in vascular permeability induced by histamine and serotonin. These results suggest that RKS has antiallergic activity in animals, and the functional antagonism of a histamine response may be one of the mechanisms of its effect. In addition, RKS prevented histamine hypersensitivity in actively sensitized mice. Because RKS did not affect sleeping time induced by pentobarbital in mice and did not inhibit gastric emptying in rats, the drug appears to be useful for treating allergic patients suffering from classical antihistamines side effects such as stomach discomfort or relative drowsiness.