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We firstly disclose single compound yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from Au22Glutathione18 (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication (EC50: ~0.24 M) and intrinsically down-regulates NF{kappa}B pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The lung viral load and inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir while their lung viral load are decreased to same level. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 golden hamsters. One Sentence SummaryWe found that gold cluster molecule directly inhibits SARS-CoV-2 replication and intrinsically suppresses inflammatory cytokines expression in COVID-19 transgenic mouse and golden hamster model, gold cluster providing a better lung injury protection than Remdesivir in COVID-19 golden hamsters via intranasally dropping administration.
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Background: Endoscopic submucosal dissection has become the preferred treatment for early gastric cancer without lymph node metastasis (LNM). The risk of LNM is different among different pathological types of early gastric cancer. Aims: To investigate the risk factors of LNM in patients with early gastric cancer. Methods: The clinicopathological features of 1 093 early gastric cancer patients underwent radical gastrectomy and diagnosed by pathology from January 2005 to December 2019 at Nanjing Drum Tower Hospital and Nanjing Gaochun People's Hospital were retrospectively analyzed. Risk factors of LNM in patients with early gastric cancer were analyzed by univariate analysis and logistic regression model analysis. Results: A total of 1 093 patients with early gastric cancer were enrolled, and positive LNM was found in 154 patients (14.1%). Univariate analysis showed that gender, age, tumor size, tumor location, gross classification, depth of tumor invasion, vascular and nerve invasion, differentiation type, ulcers were related with LNM (P<0.05). Multivariate analysis showed that age (OR=1.654, 95% CI: 1.102-2.480, P=0.015), tumor location (OR=1.617, 95% CI: 1.227-2.131, P=0.001), differentiation type (OR=1.664, 95% CI: 1.205-2.298, P=0.002), depth of invasion (OR=1.569, 95% CI: 1.212-2.030, P=0.001), vascular invasion (OR=10.514, 95% CI: 6.353-17.401, P=0.000) were the independent risk factors of LNM in early gastric cancer. Conclusions: Age, tumor location, differentiation type, depth of invasion, and vascular invasion are the independent risk factors of LNM in early gastric cancer, especially vascular invasion. For patients with vascular invasion, if there are no contraindications, surgical intervention is recommended.
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Aim To study the inotropic action of DMA in normal rat isolated hearts and papillary muscle and search for its primary mechanism.Methods With Lansendorff-perfusion and isolated papillary muscle perfusion,cardiac performance and the systolic function of papillary muscle were measured to estimate the inotropic action of DMA;L-calcium channel blocker and sodium calcium exchanger(NCX)inhibitor were used to search for its primary mechanism.Results ①(1~20)?mol?L-1 DMA exerted a positive inotropic action in normal rat isolated hearts,that is in Langendorff-perfused hearts,DMA enhanced cardiac performance,i.e.LVSP-LVDP,+dp/dtmax,-dp/dtmax significantly(P
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Objective To study the in vitro heating ability of Ni-Cu thermoseeds and their effect on the rabbit liver cells and tissues. Methods The temperature of rabbit liver tissues were monitored under an alternating magnetic field.MTT assay was used to evaluate the in vitro cytotoxicity of the extra-liquid of the Ni-Cu thermoseeds;Hemolytic test was carried out to estimate its blood toxicity;and muscular implantation test was employed to determine the levels of its tissue toxicity.Results The thermoseeds used in this experiment showed a high heating ability in alternating magnetic field in vitro.MTT assay showed that the toxicity of the material on mouse fibroblast(L-929) cell lines was 1 degree,which means non-cytotoxic.Hemolytic test revealed a hemolysis rate(HR) of 3.25%(less than 5%),showing that the thermoseeds had no hemolytic reaction.Muscular implantation test showed different levels of inflammatory reaction in the muscle tissues.Conclusion Thermoseeds induced heating in alternating magnetic field can achieve an appropriate temperature,and the gilded thermoseeds have a high biocompatibility with 1 degree cytotoxicity without leading to hemolytic reaction.
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Objective To evaluate the heating ability of thermoseeds in alternating magnetic field and its therapeutic effects on tumor bearing rats with simultaneously detected immune function. Methods To monitor the temperature increase of thermoseeds in vitro,of which the Curie point was 57 ℃ or 70 ℃.Forty Wistar rats implanted with Walker-256 cells were randomly divided into five groups: C group(control group,10 rats),M group(magnetic control group,5 rats),T group(thermoseeds control group,5 rats) and two heating treatment groups(H1 group,10 rats and H2 group,10 rats).In the H1 group,two thermoseeds with a Curie point at 57 ℃ were implanted into the tumor tissues in each rat with a heating time of 30 minutes,while in the H2 group,two thermoseeds with a Curie point at 70 ℃ were used with a heating time of 6 minutes.Five rats from each group were killed 9 days after the heating therapy to evaluate the volume and weight of the tumor tissues.The peripheral blood T-cells were counted in the rest rats in the H1,H2,and C groups. Results Magnetic inductive heating of the thermoseeds in vitro can reach the Curie point.The median tumor volume in the H2 group was 0.50 cm3(0.00-26.54),which was significantly lower than that in the M group(36.18 cm3,0.96-39.90,Z=2.21,P=0.032).And the weight of the tumors in the H1 and H2 groups was significantly lower than that in the M group [0.96 g(0.00-21.18) in H1 and 0.41 g(0.00-23.40) in H2 vs 31.45 g(1.09-36.09) in M group,Z=2.21 and P=0.032 for both].In the peripheral blood,the percentage of CD4+ T-cells was(22.39?5.27)% in H1 group,and(24.76?5.19)% in H2 group,which were significantly higher than that in C group [(12.07?4.45)%,P=0.01 and 0.003 respectively];and the percentage of CD8+ T-cells in the H2 group was significantly higher than that in the C group [(19.58?4.63)% vs(12.72?3.96)%,P=0.04].Conclusions Thermoseed had a good heating ability in alternating magnetic field and its inductive heating can inhibit tumor growth in Wistar rats and improve the immune function of the rats.
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Aim To investigate the effects and mechanisms of DMA on cardiac function in cardiomegaly rat isolated hearts.Methods With Langendorff perfusion,the changes in the indicators reflecting cardiac function were observed in cardiomegaly rat isolated hearts.Its probable mechanism was explored with calcium channel blocker and sodium calcium exchange(NCX) blockers.Results DMA(0.5～2 ?mol?L~(-1))enchanced cardiac function and exerted positive effects on LVSP-LVDP,+dp/dt_(max)and-dp/dt_(max) in Langendorff-perfused cardiomegaly rat isolated hearts.The effects of DMA on cardiac function in cardiomegaly rat isolated hearts weren′t blocked by nicardipine-one of calcium channel blockers and were blocked by NiCl_2——one of sodium calcium exchange(NCX) blockers.Conclusion DMA can enhance systolic and diastolic function in cardiomegaly rat isolated hearts.By agitating NCX,DMA enhances cardiac function in cardiomegaly rat isolated hearts,independent of L-calcium channel.
