5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH) is a slowly releasing H2S donor with some neuroprotective effect.In order to study the structure-activity relationships,seventeen compounds (Y1-Y17) were synthesized by modification of ADT-OH at the aromatic ring position,and their structures were confirmed by 1H NMR,13C NMR and HR-MS.Among them,6 compounds (Y4,Y13-Y17) were novel compounds.Their effects had been evaluated on HT-22 hippocampal neuron cells damaged by glutamate with MTF method.The pharmacological results demonstrated that all the Y compounds had potent neuroprotection at most of the tested concentrations (1-100 μmol/L).Compounds Y1-Y9 and Y11 significantly improved the survival rates of the damaged cells at 1-100 μmol/L (P ＜0.01).Specially,compounds Y1,Y4,Y6-Y9,Yu are more potent than their parent compound ADT-OH at concentration of 1-10 μmol/L,which is worthy of further study.

Objective To determine the effect and safety of metallic stents in the treatment of acute malignant colorectal obstruction.Methods From May,2000 to June,2003, self-expanding metallic stents were implanted in 15 patients with acute left colonic obstruction caused by malignancies. The postoperative remission and complications were observed.Results Stents were implanted successfully in 12 cases(80.0%,12/15).Of the 12 cases,the obstruction were all disappeared within 24h. No death or colonic perforation happened in this series. Stent migration and anal pain developed each in one case after stent implantation. Elective radical resection was performed on 8 cases after bowel preparation and supportive therapy; and stents reserved permanently in other 4 cases. Conclusions The implantation of self-expanding metallic stents is a safe and effective method for the temporary remission or permanent treatment of acute left-colonic or rectal obstruction caused by malignancies,it can instead of colostomy.

Reticular macular disease (RMD) is a novel, independent macular disease closely related to age-related macular degeneration (AMD). It is currently available to identify RMD through a variety of new imaging techniques.The infrared imaging in the confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography have the highest sensitivity and specificity for the diagnosis of RMD, and the imaging characteristics are significantly different from those of the common drusen.The cause of RMD has a certain correlation with genes, environment, gender, age and systemic diseases, but the specific pathogenesis is still inconclusive.Many studies showing that choroid vascular lesions are closely related, and Bruch membrane lesions may also be the cause of the first appearance of reticular pseudodrusen in some studies.RMD is closely related to advanced AMD, especially geographic atrophy, and some develop advanced wet-AMD.Early intervention may prevent its progression to advanced AMD.In recent years, it has been found to be associated with cardiovascular diseases and some malignant tumors, and may even become a warning sign.Therefore, research on RMD is of increasing importance in clinical implications.In this article, the characteristics of RMD, its clinical and imaging manifestations, changes of visual function and its relationship with fundus and systemic diseases were reviewed.

【Objective】 To explore and verify the mechanism of curcumin’s inhibition of the proliferation of renal clear cell carcinoma （RCCC） based on network pharmacology and bioinformatics. 【Methods】 We screened common target genes of RCCC and curcumin from PharmMapper and GeneCards databases. We used TCGA database data analysis to screen out common target genes which not only differentially expressed between RCCC tissue samples and normal tissue samples but also affected prognosis. We also used STRING platform to construct curcumin-RCCC targets interaction network， used R software to perform GO biological process analysis and KEGG pathway enrichment analysis based on the above-mentioned screening target proteins. After curcumin and/or active oxygen inhibitor N-acetyl-L-cysteine （NAC） were incubated in renal cancer 786-O and ACHN cells， CCK8 was used to detect the effects of different concentrations of curcumin on cell proliferation and cell viability. Reactive oxygen detection kit （DCFH-DA） was used to detect the level of intracellular reactive oxygen species， and malondialdehyde （MDA） determination kit （TBA method） to detect intracellular malondialdehyde changes. 【Results】 PharmMapper website and GeneCards database screened out 109 common targets of curcumin and RCCC. TCGA database data analysis screened out 37 differentially expressed genes （DEGs） that might affect the overall survival of patients. The core target proteins of curcumin screened out by protein-protein interaction （PPI） that inhibited the biological behavior of RCCC mainly involved CASP3， EGFR， CHEK1， HSP90AA1， and AR. GO enrichment analysis identified 213 items， mainly including reactive oxygen species metabolic process， response to steroid hormones， fibrinolysis and other biologically active processes. KEGG enrichment analysis identified 24 items， which were mainly related to pyruvate metabolism， glycolysis/gluconeogenesis， FoxO signaling pathway， colorectal cancer， tyrosine metabolism， IL-17 signaling pathway， apoptosis and other signaling pathways. Curcumin reduced the cell viability of 786-O and ACHN in a time- and dose-dependent manner （P<0.05）. After curcumin was incubated with kidney cancer cells， the level of reactive oxygen species and MDA increased significantly （P<0.05）. The addition of NAC reversed the effect of curcumin on the cell viability of 786-O and ACHN cells （P<0.05）. 【Conclusion】 Curcumin may participate in the oxidative stress pathway to inhibit the proliferation of renal cell carcinoma.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.