Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. @*Materials and Methods@#Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. @*Results@#APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. @*Conclusion@#APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

Tools for large-scale genetic manipulation of yeast genome / 生物工程学报

Large-scale genetic manipulation of the genome refers to the genetic modification of large fragments of DNA using knockout, integration and translocation. Compared to small-scale gene editing, large-scale genetic manipulation of the genome allows for the simultaneous modification of more genetic information, which is important for understanding the complex mechanisms such as multigene interactions. At the same time, large-scale genetic manipulation of the genome allows for larger-scale design and reconstruction of the genome, and even the creation of entirely new genomes, with great potential in reconstructing complex functions. Yeast is an important eukaryotic model organism that is widely used because of its safety and easiness of manipulation. This paper systematically summarizes the toolkit for large-scale genetic manipulation of the yeast genome, including recombinase-mediated large-scale manipulation, nuclease-mediated large-scale manipulation, de novo synthesis of large DNA fragments and other large-scale manipulation tools, and introduces their basic working principles and typical application cases. Finally, the challenges and developments in large-scale genetic manipulation are presented.

MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH), a metabolic disorder consisting of steatosis and inflammation, is considered the hepatic equivalent of metabolic syndrome and can result in irreversible liver damage. Macrophage-stimulating protein (MSP) is a hepatokine that potentially has a beneficial role in hepatic lipid and glucose metabolism via the activation of AMP-activated protein kinase (AMPK). In the current study, we investigated the regulatory role of MSP in the development of inflammation and lipid metabolism in various NASH models, both in vitro and ex vivo. We observed that MSP treatment activated the AMPK signaling pathway and inhibited lipopolysaccharide (LPS)- and palmitic acid (PA)-induced gene expression of pro-inflammatory cytokines in primary mouse hepatocytes. In addition, MSP treatment resulted in a significant reduction in PA-induced lipid accumulation and inhibited the gene expression of key lipogenic enzymes in HepG2 cells. Upon short hairpin RNA-induced knockdown of RON (the membrane-bound receptor for MSP), the anti-inflammatory and anti-lipogenic effects of MSP were markedly ablated. Finally, to mimic NASH ex vivo, we challenged bone marrow-derived macrophages with oxidized low-density lipoprotein (oxLDL) in combination with LPS. OxLDL+LPS exposure led to a marked inhibition of AMPK activity and a robust increase in inflammation. MSP treatment significantly reversed these effects by restoring AMPK activity and by suppressing pro-inflammatory cytokine gene expression and secretion under this condition. Taken together, these data suggest that MSP is an effective inhibitor of inflammation and lipid accumulation in the stressed liver, thereby indicating that MSP has a key regulatory role in NASH.

Effect on the level of T cells immunity and mechanism of apoptosis in the Oral lichen planus patients induced by the total paeony glycoside / 重庆医学

Objective Observe the effect of Total paeony glycoside(TPG)has on the T-cell immune action and apoptosis process of Oral lichen planus patients and analyze the mechanism.Methods 20 OLP patients are recruited into this experiment, each is treated with TPG,and their clinical effect is taken notes of.Observe the apoptosis of OLP lesions from each of the patients before and after the treatment,compare the apoptosis condition and the expression of CD4 + ,CD8 + ,and the CD4 +/CD8 + ratio,to analyze the role TPG plays on the immune expression of T-cell and the effect on apoptosis process.Results TPG improve the clini-cal manifestation of OLP patients significantly,resulting in the decrease of reticulum and erosive areas,and the pain index is de-creased obviously.The expression of CD4 + and CD8 + are decreased in OLP lesions after the treatment of TPG.Conclusion TPG may induce the apoptosis of the T-cell in lamina propria of the OLP lesions to regulate the T-cell immune action of OLP patients, and slow the development of inflammatory process of OLP,and in that way,TPG shows its potential in treating OLP,and this ex-periment can provide the primary evidence.

Application of the standardized nursing ward round in nursing management / 现代临床护理

Objective To probe into the effects of applying standardized nursing ward round in nursing management.Method The nursing ward round was regularly conducted to analyze and discuss the difficulties in intensive care.Results After formulating the nursing ward round,the qualification rate of the basic nursing,specific nursing,the nursing of critical paitents,nursing records and the patient's satisfaction were higher than those before the use of nursing ward round(P<0.05).Conclusion The standardized nursing ward round may strengthen the training of nurses' core ability and the initiative of studying,reduce medical disputes,and improve the satisfaction of patients together with the quality of nursing.

Coblation Nucleoplasty for Lumbar Disc Herniation / 中国微创外科杂志

Objective To explore the efficacy of coblation nucleoplasty for the treatment of lumber disc herniation.Methods A total of 40 patients with lumber disc herniation were treated with coblation nucleoplasty in our hospital.Discogram was taken before the surgery.The patients with negative results were excluded from this series.Results The operation was completed in all the 40 cases(44 interspinous spaces).They were followed up for 2 to 8 months(mean 5 months).According to the Nakano's criteria,the outcome of the surgery was excellent in 8 and good in 29,accounting for 92%(37/40)of the patients.In the patients with central type lumber disc herniation,8(80%,8/10)had excellent or good outcome;whereas,in those with lateral type herniation,97%(29)of the 30 patients had such results.None of this series had complications.Conclusion Coblation nucleoplasty is a simple,safe,and effective surgery with minimal invasion for lumber disc herniation.