Circ_0008039 supports breast cancer cell proliferation,migration, invasion,and glycolysis by regulating the miR‐140‐3p/SKA2 axis

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR‐140‐3p, and spindle and kinetochore‐associated protein 2 (SKA2) was detected by qRT‐PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR‐140‐3p and circ_0008039 or SKA2 was verified by dual‐luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR‐140‐3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR‐140‐3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR‐140‐3p and its overexpression partially inhibited the suppressive effect of miR‐140‐3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR‐140‐3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR‐140‐3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR‐140‐3p/SKA2 axis, providing an important theoretical basis for treatment of BC.

Abbreviations

ANOVA

analysis of variance

BC

breast cancer

circRNAs

circular RNAs

DMSO

dimethyl sulfoxide

ECAR

extracellular acidification rate

ECL

enhanced chemiluminescence

FBS

fetal bovine serum

HK2

hexokinase II

MEGM

mammary epithelial growth medium

miR‐140‐3p

microRNA‐140‐3p

MTT

methylthiazolyldiphenyl‐tetrazolium bromide

PBS

phosphate‐buffered saline

PRKAR1B

protein kinase A regulatory subunit R1‐beta

SD

standard ± deviation

SKA2

spindle and kinetochore‐associated protein 2

     

Prevalence and risk factors of restless legs syndrome in peritoneal dialysis patients

Objective To investigate the prevalence of restless legs syndrome (RLS) in peritoneal dialysis patients and analyze the related risk factors. Methods This study was a cross-sectional study. The patients receiving maintenance peritoneal dialysis from January 2017 to December 2017 in the Peritoneal Dialysis Center of the Second Hospital Affiliated to Soochow University were selected as the study subjects. RLS was screened for peritoneal dialysis patients by epidemiological field investigation based on the RLS diagnostic criteria of the International Restless Leg Syndrome Research Group in 2014. Clinical data and laboratory examinations of selected patients were collected and the differences of clinical indicators between RLS and non-RLS patients were compared. The risk factors related to RLS were analyzed by logistic regression. Results Seventy-six cases of RLS were screened out from 396 PD patients. The prevalence of RLS was 19.2%. Compared with non-RLS group, RLS group patients had longer dialysis age, less 24 hours urine volume, and elevated blood intact Parathormone (iPTH) and alkaline phosphatase (AKP) (all P﹤0.05). There was no significant difference in primary disease ratio, sex, age, body mass index, blood pressure, hemoglobin, creatinine, urea nitrogen, uric acid, ferritin, serum iron, transferrin saturation, blood calcium, blood phosphorus, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, eGFR, Kt/V, Ccr between RLS and non-RLS group patients (all P﹥0.05). Multivariate logistic regression analysis showed that long dialysis age (OR=1.010, 95%CI 1.001-1.018, P=0.022) and high blood AKP (OR=1.005, 95%CI 1.001-1.010, P=0.021) were independent risk factors for RLS in peritoneal dialysis patients (both P﹤0.05). Conclusions The prevalence of RLS is high in peritoneal dialysis patients. Long dialysis age and high blood AKP are independent risk factors for RLS.     

Role of Oxalobacter formigenes in preventing calcium oxalate kidney stones

Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults, and study its effect on the the prevention of calcium oxalate kidney stones. Methods OxF was screened and cultured from fresh feces of healthy adults. The rat model of calcium oxalate stone was established by esophageal gavage of 0.8% of ethylene glycol. Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table. Three groups were treated with 106 CFU, 107 CFU, 108 CFU viable OxF every day, respectively, for 4 weeks. The blood and 24-hour urine samples were collected to detect the serum creatinine, urea nitrogen, serum and urine calcium, phosphorus, magnesium and urine oxalate every week. At the end of the 4th week, the rats were sacrificed and the kidney tissues were stained with HE and Yasue. The deposition and content of calcium oxalate crystals were observed under a light microscope. Results The bacteria strain isolated from fresh feces of healthy adults was 100% as same as the known ATCC35274 bacteria strain, which means the strain screened is OxF. Among the 5 groups, there were no significant differences in body weight, Scr, BUN, serum calcium, blood magnesium, blood phosphorus, urinary magnesium and urinary phosphorus. The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P＜0.05). After intervention with OxF solution, the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P＜0.05), while there was no significant difference between the other intervention groups and the model. The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model, but the difference did not reach statistical significance (P＞0.05). The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P＜0.05), and continued to decrease for the next 3 weeks. After 4 weeks of intervention, no crystal formation was observed in the control group under the deflection microscope, but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla. The crystals were piled up and connected to each other. Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys. Compared with the model, there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group, while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P＜0.05). Conclusions OxF are successively screened from healthy adults. Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion, prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats.     

温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响

目的:观察温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响。方法:选取2015年7月至2017年8月青海省中医院收治的高原类风湿关节炎患者132例作为研究对象,随机分为对照组和观察组,每组66例。对照组应用常规西医治疗,观察组在对照组治疗基础上应用温阳补肾法治疗,2组均连续治疗3个月。比较2组治疗后临床疗效,统计2组治疗前后主要临床症状与体征、健康状况评定量表(HAQ)评分和DAS28评分,检测2组治疗前后实验室检查指标、血清25羟维生素D3以及血液流变学指标水平。结果:治疗后,观察组临床治疗总有效率显著高于对照组(P 0. 05); 2组关节肿胀指数、关节疼痛指数、关节压痛指数、晨僵时间、关节功能分级和20 m步行时间均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组HAQ评分、DAS28评分、类风湿因子(RF)、C反应蛋白(CRP)和红细胞沉降率(ESR)水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组血清25羟维生素D3水平均较治疗前显著升高(P 0. 05),且观察组显著高于对照组(P 0. 05); 2组红细胞电泳指数、红细胞压积、血浆黏度、全血低切黏度、全血高切黏度水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05)。结论:温阳补肾法治疗高原类风湿关节炎,疗效满意,同时能明显增加血清25羟维生素D3水平。     

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study

BackgroundThe current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.MethodsTaking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR−), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.ResultsThe accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87–0.91, 0.89–0.92, 0.87–0.91, and 0.86–0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).ConclusionsThe CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.Trial registrationChictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.     

Efficient drug discovery by rational lead hybridization based on crystallographic overlay

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升髓合剂防治化疗后骨髓抑制的临床研究

目的:观察患者临床症状、客观检测指标及用药期间是否出现不良反应等,评价升髓合剂对多西他赛联合顺铂方案(Docetaxel Combined with Cis-platinum,DP)化疗所致骨髓抑制的有效性及安全性。方法:将50例符合标准的恶性肿瘤患者随机分为两组,治疗组和对照组各25例。对照组:DP方案化疗同时加服地榆升白片,治疗组:在DP方案化疗基础上加用升髓合剂。2个周期后观察患者化疗后第3、7、14 d外周血细胞变化及骨髓抑制情况,化疗后中医临床症状评分及疗效以及体力状况评分(Karnofsky,KPS)、体质量变化及其不良反应。结果:①两组化疗完成率观察组明显高于对照组(P<0.05);②观察组血常规中白细胞、中性粒细胞、血小板计数治疗后1周与治疗前比较无统计学意义,(P>0.05),而对照组白细胞、中性粒细胞、血小板计数下降显著,与治疗前差异有统计学意义,(P<0.05);两组相比,化疗后1周观察组血常规白细胞、中性粒细胞、血小板水平明显高于对照组,差距有统计学意义(P<0.05);③化疗后2周观察组白细胞计数升高明显高于对照组,两组差异有显著性(P<0.05);④化疗后中医证候改善方面,观察组症状改善显著(P<0.05)。对照组症状上改善不明显(P>0.05),两组在总体症状改善率方面相比较有显著性差异,治疗组明显优于对照组(P<0.05);⑤治疗组KPS评分明显优于对照组(P<0.05);⑥治疗组不良反应的发生率明显低于对照组(P<0.05)。结论:升髓合剂对于多西他赛联合顺铂化疗方案引起的骨髓抑制等不良反应具有防治作用。     

Role of Aggregatibacter actinomycetemcomitans in glutathione catabolism

Introduction:  Our previous studies demonstrated that three enzymes, γ-glutamyltransferase (GGT), cysteinylglycinase (CGase) and cystalysin, are required for the catabolism of glutathione to produce hydrogen sulfide (H₂S) in Treponema denticola . In this study, we examined glutathione catabolism in Aggregatibacter actinomycetemcomitans .
Methods:  The GGT and CGase of A. actinomycetemcomitans were determined by biological methods and GGT was characterized using a molecular biological approach.
Results:  A. actinomycetemcomitans showed GGT and CGase activity, but could not produce H₂S from glutathione. The addition of recombinant T. denticola cystalysin, an l -cysteine desulfhydrase, to whole cells of A. actinomycetemcomitans resulted in the production of H₂S from glutathione. Subsequently, we cloned A. actinomycetemcomitans GGT gene ( ggt ) and overexpressed the 63 kDa GGT protein. The recombinant A. actinomycetemcomitans GGT was purified and identified. The K _cat/ K _m of the recombinant GGT from N -γ- l -glutamyl-4-nitroaniline as substrate was 31/μ m /min. The activity of GGT was optimum at pH 6.9–7.1 and enhanced by thiol-containing compounds.
Conclusion:  The results demonstrated that A. actinomycetemcomitans had GGT and CGase activities and that the GGT was characterized. The possible role of A. actinomycetemcomitans in glutathione metabolism and H₂S production from oral bacteria was discussed.     

糖尿病病人胰岛素泵应用及相关知识调查

[目的]探讨糖尿病病人应用胰岛素泵强化治疗的相关知识及需求情况.[方法]采用自行设计的问卷调查表,对60例糖尿病胰岛素泵强化治疗病人进行调查.[结果]病人对胰岛素泵了解甚少,相关知识缺乏,希望接受胰岛素泵知识教育.[结论]胰岛素泵应用现状存在较多问题,影响病人血糖的良好控制,应提高病人对胰岛素泵的认可程度和依从性,提高生活质量.