;~lasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs （shRNA） can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 （GRIM-19）. Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium （S. typhimurium） to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitroand in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.

羟基磷灰石纳米粒子携带Si-Star3质粒抑制小鼠前列腺癌生长的体外研究

DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.

Clinical characteristics of intrahepatic biliary papilloma:A case report

BACKGROUND Intrahepatic bile duct papilloma(IPNB)is a rare benign tumour from the bile duct epithelium and has a high malignant transformation rate.Early radical resection can obviously improve the prognosis of patients,but it is difficult to be sure of the diagnosis of IPNB before operating.CASE SUMMARY This study included 28 patients with intraductal papilloma admitted to the First Hospital of Jilin University from January 2010 to November 2020 and recorded their clinical manifestations,imaging features,complications and prognosis.There were 12 males and 16 females with an average age of 61.36±8.03 years.Most patients had symptoms of biliary obstruction.Biliary dilatation and cystic mass could be seen on imaging.After surgery,IPNB was diagnosed by pathology.CONCLUSION IPNB is a rare benign tumour in the bile duct.Early diagnosis and timely R0 resection can improve the prognosis of IPNB.

Novel m.4268T>C mutation in the mitochondrial tRNA^(Ile) gene is associated with hearing loss in two Chinese families

BACKGROUND Herein,we report the genetic,clinical,molecular and biochemical features of two Han Chinese pedigrees with suggested maternally transmitted non-syndromic hearing loss.AIM To investigate the pathophysiology of hearing loss associated with mitochondrial tRNA mutations.METHODS Sixteen subjects from two Chinese families with hearing loss underwent clinical,genetic,molecular,and biochemical evaluations.Biochemical characterizations included the measurements of tRNA levels using lymphoblastoid cell lines derived from five affected matrilineal relatives of these families and three control subjects.RESULTS Three of the 16 matrilineal relatives in these families exhibited a variable seriousness and age-at-onset(8 years)of deafness.Analysis of mtDNA mutation identified the novel homoplasmic tRNA^(Ile) 4268T>C mutation in two families both belonging to haplogroup D4j.The 4268T>C mutation is located in a highly conserved base pairing(6U–67A)of tRNA^(Ile).The elimination of 6U–67A basepairing may change the tRNA^(Ile) metabolism.Functional mutation was supported by an approximately 64.6%reduction in the level of tRNA^(Ile) observed in the lymphoblastoid cell lines with the 4268T>C mutation,in contrast to the wild-type cell lines.The reduced level of tRNA was below the proposed threshold for normal respiration in lymphoblastoid cells.However,genotyping analysis did not detect any mutations in the prominent deafness-causing gene GJB2 in any members of the family.CONCLUSION These data show that the novel tRNA^(Ile) 4268T>C mutation was involved in maternally transmitted deafness.However,epigenetic,other genetic,or environmental factors may be attributed to the phenotypic variability.These findings will be useful for understanding families with maternally inherited deafness.

Clinical characteristics of adult-type annular pancreas:A case report

BACKGROUND Annular pancreas(AP)is a rare congenital abnormal rotation of the pancreas.AP rarely occurs in adults.Pancreatic tumors and ampullary tumors are related to AP,so the discovery and treatment of AP are essential.CASE SUMMARY This study investigated the clinical manifestations,imaging features,complications,and treatment of six patients diagnosed with AP at the Department of Hepatobiliary and Pancreatic Surgery,First Hospital of Jilin University from January 2010 to June 2020.There were four males and two females,with an average age of 56.00±9.86 years old.In this study,abdominal pain and jaundice were the main clinical manifestations.Imaging can show the“crocodile jaw sign”or“double bubble sign”.CONCLUSION For patients with duodenal or biliary obstruction,physicians should give priority to AP when imaging examinations suggest that the duodenum is wrapped with tissue similar to the density of the pancreas.Symptomatic patients should actively undergo surgical treatment.

DEMC: A Deep Dual-Encoder Network for Denoising Monte Carlo Rendering

In this paper, we present DEMC, a deep dual-encoder network to remove Monte Carlo noise efficiently while preserving details. Denoising Monte Carlo rendering is different from natural image denoising since inexpensive by-products (feature buffers) can be extracted in the rendering stage. Most of them are noise-free and can provide sufficient details for image reconstruction. However, these feature buffers also contain redundant information. Hence, the main challenge of this topic is how to extract useful information and reconstruct clean images. To address this problem, we propose a novel network structure, dual-encoder network with a feature fusion sub-network, to fuse feature buffers firstly, then encode the fused feature buffers and a noisy image simultaneously, and finally reconstruct a clean image by a decoder network. Compared with the state-of-the-art methods, our model is more robust on a wide range of scenes, and is able to generate satisfactory results in a significantly faster way.