Supplementary Figure from Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction
This research aims to analyze the differences in bone healing rate, cytokines content, and growth factor content in rats with fracture and traumatic brain injury. In this study, rat models of tibial fracture (fracture group) and tibial fracture combined with brain injury (combined group) were first constructed. Callus and brain tissue sections of the two groups of rat models were made, and the pathological changes were analyzed by hematoxylin – eosin staining. Tissue sections were made to compare the differences in callus volume, trabecular width, and trabecular bone ratio between the two groups of rats. Taking normal rats as controls, serum samples were collected from rats in the control group, fracture group, and combined group. The differences of levels in nerve growth factor (NGF), insulin-like growth factor 1 (IGF1), bone morphogenetic protein 7 (BMP7), and transforming growth factor β1 (TGFβ1) in serum of different groups of rats were detected by enzyme-linked immunosorbent assay, and the expression of NGF, IGF 1, BMPR7, and TGFβR1 in rat callus was detected by Western-Blot. It was found that the rate of bone healing in the combined group was faster than that in the fracture group. The bone callus volume, trabecular width, and trabecular proportion of the rats in the combined group were significantly higher than those in the fracture group (P < 0.05). The content of NGF, IGF1, BMP7, and TGFβ1 in the serum of the fracture group and the combined group and the expression of their receptor proteins were significantly higher than that of the control group (P < 0.05), but the content of NGF, IGF1, BMP7, and TGF 1 in the serum and the expression of their receptor proteins of the combined group were significantly higher than that of the fracture group (P < 0.05). Accordingly, tibial fractures combined with brain injury can accelerate bone healing, which may be caused by regulating the expression of NGF, IGF1, BMP7, and TGFβ1 and accelerating the binding of its receptors.
Abstract Background and Aims Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. Methods Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. Results Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I–II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. Conclusion Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. Chinese Clinical Trial Registry Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .
Background Chronic liver injury (CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin (DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosis-related molecules. Therefore, we studied the influence of DHM on CLI and pyroptosis. Aim To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of DHM. Methods Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride (CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-β-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related molecules. Results Serum total cholesterol, low density lipoprotein, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and gasdermin D (GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these proteins in the DHM group was lower than that in the vehicle group. Quantitative reverse transcription PCR results showed that the expression of the pyroptosis-related genes caspase-1, NLRP3, GSDMD and interleukin-1β (IL-1β) in the CCl4 group was higher than that in the control group, while there was no significant change in NLRP3 and caspase-1 expression in the DHM group compared with that in the vehicle group, and the expression of GSDMD and IL-1β was decreased. Conclusion DHM improves CCl4-induced CLI and regulates the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic agent for CLI.
Both tea polysaccharides (TPS) and tea polyphenols (TPP) are promising in the treatment of inflammatory bowel disease (IBD). However, the effects of their combination against IBD are still unknown. In the present study, the therapeutic effects of TPS, TPP and TPS + TPP on dextran sodium sulfate-induced colitis in mice were investigated. Our results showed that administration of TPS + TPP achieved the best effects, followed by TPP and TPS, which were evidenced by the restoration of various physical signs (body weight, colon length and disease activity index) and the promoted intestinal barrier function (colon damage, mucin secretion and tight junction proteins expression). Furthermore, TPP and TPS decreased the relative abundance of Proteobacteria and Enterobacteriaceae, while TPP + TPS increased that of Lactobacillaceae and Lactobacillus. In conclusion, TPS together with TPP had greater effects on alleviating colitis and promoting intestinal barrier function. This result is interesting when developing functional foods against colitis.
Supplementary Figure from Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction
Objective To observe the effect and clinical toxicity of pemetrexed combined with carboplatin versus paclitaxel combined with carboplatin with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC).Methods Total of 60 patients stage Ⅲ NSCLC (ⅢA 39 patients,ⅢB 21 patients) were randomly assigned into two groups.Pemetrexed combined with carboplatin group:accepted pemetrexed 500 mg/m2,d1,carboplatin AUC 5,d1,once every 21 days.Paclitaxel combined with carboplatin group:paclitaxel 150 mg/m2,d1,carboplatin AUC 5,d1,once every 21 days.Two groups both accepted 3-D conformal radiation therapy (3D-CRT) during chemotherapy.The total dose was 60 ～ 70 Gy.After radiation therapy,the patients were accepted 2 ～ 3 cycles of chemotherapy.Results The efficacy of pemetrexed combined with carboplatin and paclitaxel combined with carboplatin were 44.83％ and 29.03％ respectively.The disease control rates of two groups were 79.31％ and 67.74％ respectively.The differences were statistically significant (P＜0.05).The adverse reactions of pemetrexed group were rare.Two groups of median progression-free survival were 12.5 and 9.9 months respectively.1 year overall survival was 58.62％ and 48.39％ respectively.The differences were also significant (P＜0.05).Conclusion Pemetrexed combined with carboplatin can be used as stage Ⅲ NSCLC patients treated with concurrent chemoradiation regimens during optimization.Toxicity was tolerable.Pemetrexed group was better than paclitaxel group in disease control rates and survival.
Key words:
Pemetrexed; Paclitaxel; Concurrent chemoradiotherapy; Non-small cell lung cancer
Remote ischemic postconditoning, a phenomenon in which brief ischemic stimuli of 1 organ protect another organ against an ischemic insult, has been demonstrated to protect the myocardium and adult brain in animal models. However, mediators of the protection and underlying mechanisms remain to be elucidated. In the present study, we tested the hypothesis that remote limb ischemic postconditioning applied immediately after hypoxia provides neuroprotection in a rat model of neonatal hypoxia-ischemia (HI) by mechanisms involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.HI was induced in postnatal Day 10 rat pups by unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia and reperfusion on both hind limbs immediately after HI. The opioid antagonist naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist morphine was administered to determine underlying mechanisms. Infarct volume, brain atrophy, and neurological outcomes after HI were evaluated. Expression of phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western blotting.Limb ischemic postconditioning significantly reduced infarct volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone and wortmannin abrogated the postconditioning-mediated infarct-limiting effect. Morphine given immediately after hypoxia also decreased infarct volume. Furthermore, limb ischemic postconditioning recovered Akt activity and decreased Bax expression, whereas no differences in phosphorylated ERK1/2expression were observed.Limb ischemic postconditioning protects against neonatal HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.
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