Noncoding telomeric repeat‐containing RNA inhibits the progression of hepatocellular carcinoma by regulating telomerase‐mediated telomere length

Telomeric repeat‐containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor‐1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor‐1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA‐65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.     

[Sar1, Ile4, Ile8]‐angiotensin II Potentiates Insulin Receptor Signalling and Glycogen Synthesis in Hepatocytes

The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]‐angiotensin II (SII Ang II) analogue, that only activate a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance. Here, we studied the effect of SII Ang II on insulin receptor (IR) signalling and glucose metabolism in primary rat hepatocytes. We show that long‐term pre‐treatment of hepatocytes with SII Ang II increased insulin‐stimulated glycogen synthesis, while Ang II and the AT1R antagonist losartan had no effect. Insulin‐stimulated suppression of hepatic glucose output was not affected by Ang II or SII Ang II. It is well known that insulin regulates glycogen synthesis and glucose output through Akt‐mediated phosphorylation of glycogen synthase kinase α/β (GSK3α/β) and forkhead box protein O1 (FOXO1), respectively. In line with this, we show that SII Ang II potentiated insulin‐stimulated phosphorylation of Akt and GSK3α/β, but not FOXO1. Furthermore, we demonstrate that the effect of SII Ang II on insulin‐stimulated signalling and glycogen synthesis was dependent on Src and Gαq, as inhibitors of these proteins abolished the potentiating effect of SII Ang II. Thus, our results demonstrate that SII Ang II may have a positive effect on IR signalling and glucose metabolism in hepatocytes.     

高分辨弥散加权成像在心房颤动导管消融围术期无症状脑栓塞发生的评估价值

目的比较高分辨弥散加权成像（hDWI）和常规DWI（cDWI）检测心房颤动（房颤）导管消融相关无症状性脑栓塞（ACE）的发生率及其特征。 方法连续入组2018年11月至2018年12月南京医科大学第一附属医院的32例房颤消融患者,以及上海市东方医院2019年1月至2019年2月的18例房颤消融患者。消融前24 h进行头颅高分辨率DWI检查以除外近期脑栓塞事件,消融后48 h内重复hDWI和cDWI检查。比较同一患者消融术后hDWI与cDWI中ACE的发生率、数量、大小和位置。 结果与cDWI相比,hDWI显示急性ACE的发生率更高（70%对42%,P<0.001）,ACE病灶数量明显更多（102对42,P < 0.001）,且hDWI测量的病灶尺寸较大（5.42 mm对4.21 mm,P < 0.001）。多因素回归分析显示,左心室射血分数受损（P=0.047）和术中激活凝血时间较低（P=0.003）与ACE发生相关。 结论hDWI能够更好地显示房颤消融相关ACE的发病情况及病灶特点。在评估ACE的研究中应考虑磁共振设置。     

GRIN1突变相关发育迟缓患儿临床特征和基因突变特点分析

目的 对GRIN1基因突变相关发育迟缓患儿的临床特征及基因突变特点进行分析.方法 收集2例发育迟缓患儿的临床资料,对2例患儿及其父母进行靶向基因测序(TGS).结合文献分析发育迟缓患儿的临床特征和基因突变特点.结果 2例患儿均表现为精神发育迟缓、语言落后、运动落后,无特殊面容,无癫痫,其中1例合并矮小症.TGS结果显示...     

A non-invasive model for predicting liver fibrosis in HBeAg-positive patients with normal or slightly elevated alanine aminotransferase

Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population.A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group.The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age −2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] −0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 ×  aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of −2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis.In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.     

Molecular identification of Wolbachia from the filarial nematode Mansonella perstans

Wolbachiae are bacterial endosymbionts of insects and many filarial nematodes whose products trigger inflammation in filarial infections. The dependence of the parasites on their endosymbionts has also led to the use of antibiotics directed against the Wolbachiae, therapy that has been demonstrated to have a profound salutary effect on filarial infections. The identification of Wolbachiae in Mansonella species has been conclusively shown for Mansonella ozzardi (Mo), but not for Mansonella perstans (Mp). Using primers known to amplify the 16S ribosomal DNA of other filarial Wolbachiae, an identical 1393bp band was found in all samples tested. Sequence analysis of these samples demonstrated a single consensus sequence for Mp Wolbachia 16S rDNA that was most similar to Wolbachia sequences from other filarial nematodes. When aligned with the only other Mansonella Wolbachia sequence (Mo) there were only 8 nucleotide differences in the 1369bp overlapping sequence. Phylogenetic dendrograms, examining the relationship of the Mp Wolbachia to other Wolbachia 16S rDNA, showed that the Wolbachia tracked almost identically to the 5S rRNA of their parasite host. Wolbachia surface protein (WSP) was also demonstrated in protein extracted from Mp-containing whole blood. In advance of a treatment trial of Mp, a method for the quantitation of Mp Wolbachia was developed and used to demonstrate not only a relationship between microfilarial numbers and Wolbachia copy numbers, but also to demonstrate the effect of antibiotic on ridding Mp of Wolbachia.     

Dendritic cells, pro-inflammatory responses, and antigen presentation in a rodent malaria infection

Summary: An infection of mice with Plasmodium chabaudi is characterized by a rapid and marked inflammatory response with a rapid but regulated production of interleukin‐12 (IL‐12), tumor necrosis factor‐α (TNF‐α), and interferon‐γ (IFN‐γ). Recent studies have shown that dendritic cells (DCs) are activated in vivo in the spleen, are able to process and present malaria antigens during infection, and may provide a source of cytokines that contribute to polarization of the CD4 T‐cell response. P. chabaudi‐infected erythrocytes are phagocytosed by DCs, and peptides of malaria proteins are presented on major histocompatibility complex (MHC) class II. The complex disulfide‐bonded structure of some malaria proteins can impede their processing in DCs, which may affect the magnitude of the CD4 T‐cell response and influence T‐helper 1 (Th1) or Th2 polarization. DCs exhibit a wide range of responses to parasite‐infected erythrocytes depending on their source, their maturational state, and the Plasmodium species or strain. P. chabaudi‐infected erythrocytes stimulate an increase in the expression of costimulatory molecules and MHC class II on mouse bone marrow‐derived DCs, and they are able to induce the production of pro‐inflammatory cytokines such as IL‐12, TNF‐α, and IL‐6, thus enhancing the Th1 response of naïve T cells. IFN‐γ and TNF‐α play a role in both protective immunity and the pathology of the infection, and the inflammatory disease may be regulated by IL‐10 and transforming growth factor‐β. It will therefore be important to elucidate the host and parasite molecules that are involved in activation or suppression of the DCs and to understand the interplay between these opposing forces on the host response in vivo during a malaria infection.     

Specific effects of endurance and sprint training on protein expression of calsequestrin and SERCA in mouse skeletal muscle

Calsequestrin (CSQ) is the main Ca2? binding protein inside the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. The present study demonstrates the specific effects of different training regimens on CSQ isoform 1 (CSQ1, the primary isoform) and SR Ca2?-ATPase (SERCA1, 2) expression in various skeletal muscles of mouse. CSQ1, SERCA1, and SERCA2 protein expression was determined with Western blot in m. soleus (SOL), m. extensor digitorum longus (EDL), m. gastrocnemius (GAS), m. rectus femoris (RF), and m. tibialis anterior (TA) muscles after completing a 6-week endurance or sprint training program. Endurance training induced decrease in CSQ1 concentration in SOL (p < 0.001) and in SERCA1 levels in GAS (p < 0.05), whereas increase in CSQ1 expression was detected in EDL (p < 0.01). After sprint training the concentration of CSQ1 increased in GAS (p < 0.01) and EDL (p < 0.01). Additionally, sprint exercise induced an increase in SERCA1 in GAS (p < 0.001) and a decline in TA (p < 0.05). SERCA2 was up-regulated with sprint training in GAS (p < 0.01). Myosin heavy chain (MHC) based fibre type composition altered differently depending on the muscle and the training regimen.These results indicate that (1) diverse training strategies used affect differently CSQ1 and SERCA1 concentrations in the skeletal muscle, (2) the regulation of CSQ1 and SERCA1 does not necessary follow the fast-slow definition despite the correlation between MHC isoforms, and (3) the changes in CSQ1 concentration occur prior to SERCA1 or SERCA2.     

镍钛形状记忆合金骨板形状恢复能力测试方法的研究

目的 建立镍钛形状记忆合金骨板形状恢复能力测试方法.方法 首先确定镍钛形状记忆合金骨板形状恢复能力标准评价体系需要测试相变温度、形状恢复力、形状恢复率,然后分别建立骨板相变温度、形状恢复力、形状恢复率的标准测试方法.因各企业生产的镍钛形状记忆合金骨板形状结构不同,为保证测试方法的统一性,测试采用标准试样代替,试样使用原材料与被替代产品的原材料为同一批次,机械加工处理工艺保持一致.结果 根据已上市产品技术文件,镍钛形状记忆合金骨板相变温度Af点为37℃,产品形状恢复率应大于95％.按照本文提供的相变温度、形状恢复力、形状恢复率测试方法,试样测试时恢复至原始形状相对应的温度为37℃,即镍钛形状记忆合金骨板的Af点为37℃;依据镍钛形状记忆合金骨板临床使用时的温度,将试样测试温度设置为37℃,试样在31℃～37℃温度区间恢复力数据曲线一直上升,到达峰值后趋于稳定状态,通过数据分析,峰值的恢复力数据即镍钛形状记忆合金骨板工作时的形状恢复力,试样形状恢复力测试结果平均值为64.18 N;两种试样测试形状恢复率,并计算分析数据,所有试样形状恢复率均大于95％,与厂家提供的技术文件相符合.结论 结果说明提供的镍钛形状记忆合金骨板形状恢复能力(相变温度、形状恢复力、形状恢复率)的测试标准方法,可为企业的质量监管提供依据,为监管部门提供监管指南,按照测试方法通过测试评价后可保证产品临床使用的安全性.     

Long‐TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat

Cross‐talk between adipose tissue and liver is disturbed in the metabolic syndrome. Moreover, the relative fatty acid composition of adipose and liver fat is poorly characterized. Long‐TE ¹H MRS can determine the unsaturation and polyunsaturation of adipose tissue. The aim of this study was to use long‐TE ¹H MRS to determine the composition of liver fat and its relation to adipose tissue composition. Sixteen subjects with increased liver fat (>5%) were recruited for the study. Using TE = 200 ms, we were able to resolve the olefinic (?CH, 5.3 ppm) and water (H₂O, 4.7 ppm) resonances in liver spectra and to obtain a repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%). With TE = 135 ms, the diallylic (?C? CH₂? C?, 2.8 ppm) resonance was detectable in subjects with a liver fat content above 15%. Long‐TE ¹H MRS was also used to determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose tissue in the same subjects. Liver fat was more saturated (double bonds per fatty acid chain, 0.812 ± 0.022) than subcutaneous (double bonds per fatty acid chain, 0.862 ± 0.022, p < 0.0004) or visceral (double bonds per fatty acid chain, 0.865 ± 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R = 0.879, p < 0.0004). The present study introduces a new noninvasive method for the assessment of the composition of liver fat. The results suggest that liver fat is more saturated than subcutaneous or visceral adipose tissue, which may be attributed to differences in de novo lipogenesis. Copyright © 2010 John Wiley & Sons, Ltd.