LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability.

Genomic instability (GIN) is pivotal in regulating tumor drug resistance, which blocked the treatment of triple negative breast cancer (TNBC). Although recent studies implied that non-coding RNA (ncRNA)-mediated autophagy abolishment promoted tumorigenesis by up-regulation of GIN, autophagy was known as a risk factor in tumor drug resistance. However, previous study also pointed that up-regulation of autophagy promoted GIN. Therefore, the relationship between autophagy and GIN is not clear, and more work is needed. And, if an ncRNA is identified to be a co-regulator of autophagy and GIN, it will be a potential therapy target of chemotherapy resistance in TNBC. In our study, we recognized both autophagy-GIN-associated microRNA (mi-26a-5p) by big data analysis, which was prognosis-correlated in breast cancer. Next, we identified the up-stream regulators (long non-coding RNA, lncRNA) and down-stream targets of miR-26a-5p by bioinformatics analysis (online public databases). Finally, we established lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signaling pathway, and verified their functions by cytological, molecular biological and zoological experiments. In general, our study found (1) miR-26a-5p was a protective factor of breast cancer, while OTUD6B-AS1 and MTDH were risk factors; (2) OTUD6B-AS1 was the up-stream regulator of miR-26a-5p verified by luciferase; (3) up-regulation of miR-26a-5p and down-regulation of MTDH promoted cellular cytotoxicity of paclitaxel (PTX) in vitro and in vivo. (4) down-regulation of miR-26a-5p, overexpression of MTDH and OTUD6B-AS1 promoted autophagy and DNA damage; (5) up-regulation of OTUD6B-AS1 and MTDH inhibited DNA damage response (DDR) by inhibiting the phosphorylated activation of RAD51, ATR and ATM.

Clinical Study on Dialectical Treatment of Modified Xiangsha Liu Junzitang to Diabetes Gastroparesis with Weakness Syndrome of Spleen and Stomach / 中国实验方剂学杂志

Objective:This study aims to investigate the clinical efficacy of Modified Xiangsha Liu Junzitang in the treatment of diabetic gastroparesis （DGP） and its influence on gastrointestinal hormones and oxidative stress. Method:In this study， 128 patients were randomly divided into control group （64 cases） and observation group （64 cases） . Patients in two groups took domperidone tablets orally 30 minutes before meals， 10 mg/time， 3 times/day. Patients in control group took Shenling Baizhusan San， 6 g/time， twice a day. Patients in observation group were prescribed addition and subtraction therapy of Modified Xiangsha Liu Junzitang， 1 dose/day. The course of treatment for both groups was 4 weeks. Before and after treatment， scores of gastroparesis cardinal symptom index （GCSI）， and gastric emptying test and electrogastrogram were noted. Before the treatment， scores of traditional Chinese medicine （TCM） syndrome and health survey summary were graded（SF-36）. The levels of gastrin （GAS）， motilin （MTL）， vasoactive intestinal peptide （VIP）， somatostatin （SS）， superoxide dismutase （SOD）， reactive oxygen species （ROS） and malondialdehyde （MDA） were measured before and after treatment. And adverse reactions during treatment were recorded. Result:The scores of postprandial abdominal distension/early satiety， nausea and vomiting， abdominal distention and the total scores of GCSI in the observation group were lower than those in control group （<italic>P</italic><0.01）. The gastric emptying rate in observation group was higher than that in control group （<italic>P</italic><0.01）， and the score of TCM syndromes was lower than that of control group （<italic>P</italic><0.01）. The scores of SF-36 in observation group were higher than those in control group （<italic>P</italic><0.01）. The frequency of gastric electricity and gastric electric vibration before and after the meal in observation group were higher than that in control group （<italic>P</italic><0.01）. The levels of GAS， MTL， VIP， ROS and MDA in observation group were lower than those in control group （<italic>P</italic><0.01）， while the levels of SS and SOD were higher than that of control group （<italic>P</italic><0.01）. The total effective rate in observation group was 93.75% （60/64）， which was higher than 79.69% （51/64） （<italic>χ</italic>²=5.494， <italic>P</italic><0.05） in control group （<italic>P</italic><0.01）. And no adverse reactions were found in the clinical observation. Conclusion:Modified Xiangsha Liu Junzitang combined with prokinetic drugs in the treatment of DGP patients can reduce the clinical symptoms of DGP， enhance gastrointestinal motility， improve the gastric emptying rate， improve the quality of life， regulate the level of gastrointestinal hormones， and reduce the damage of autonomic nerve caused by oxidative stress， with good comprehensive clinical effect and safety in application.

Simple Sample Preparation Method for Direct Microbial Identification and Susceptibility Testing From Positive Blood Cultures.

Rapid identification and determination of the antibiotic susceptibility profiles of the infectious agents in patients with bloodstream infections are critical steps in choosing an effective targeted antibiotic for treatment. However, there has been minimal effort focused on developing combined methods for the simultaneous direct identification and antibiotic susceptibility determination of bacteria in positive blood cultures. In this study, we constructed a lysis-centrifugation-wash procedure to prepare a bacterial pellet from positive blood cultures, which can be used directly for identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and antibiotic susceptibility testing by the Vitek 2 system. The method was evaluated using a total of 129 clinical bacteria-positive blood cultures. The whole sample preparation process could be completed in <15 min. The correct rate of direct MALDI-TOF MS identification was 96.49% for gram-negative bacteria and 97.22% for gram-positive bacteria. Vitek 2 antimicrobial susceptibility testing of gram-negative bacteria showed an agreement rate of antimicrobial categories of 96.89% with a minor error, major error, and very major error rate of 2.63, 0.24, and 0.24%, respectively. Category agreement of antimicrobials against gram-positive bacteria was 92.81%, with a minor error, major error, and very major error rate of 4.51, 1.22, and 1.46%, respectively. These results indicated that our direct antibiotic susceptibility analysis method worked well compared to the conventional culture-dependent laboratory method. Overall, this fast, easy, and accurate method can facilitate the direct identification and antibiotic susceptibility testing of bacteria in positive blood cultures.

Diagnostic strategies and the incidence of prostate cancer: reasons for the low reported incidence of prostate cancer in China / 亚洲男科学杂志(英文版)

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer (IARC), the age-standardized incidence of prostate cancer in China is 1.6/10(5) person years (PY), with a mortality rate of 1.0/10(5) PY and mortality-to-incidence rate ratio (MR/IR) = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia (MR/IR = 0.57) and much higher than that in North America (MR/IR = 0.13). These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen (PSA) screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.