Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Treatment strategy for pancreatic head cancer with celiac axis stenosis in pancreaticoduodenectomy:A case report and review of literature

BACKGROUND During pancreaticoduodenectomy in patients with celiac axis(CA)stenosis due to compression by the median arcuate ligament(MAL),the MAL has to be divided to maintain hepatic blood flow in many cases.However,MAL division often fails,and success can only be determined intraoperatively.To overcome this problem,we performed endovascular CA stenting preoperatively,and thereafter safely performed pancreaticoduodenectomy.We present this case as a new preoperative treatment strategy that was successful.CASE SUMMARY A 77-year-old man with a diagnosis of pancreatic head cancer presented to our department for surgery.Preoperative assessment revealed CA stenosis caused by MAL.We performed endovascular stenting in the CA preoperatively because we knew that going into the operation without a strategy could lead to ischemic complications.Double-antiplatelet therapy(DAPT)–which is needed when a stent is inserted–was then administered in parallel with neoadjuvant chemotherapy(NAC).This allowed us to administer DAPT for a sufficient period before the main pancreaticoduodenectomy procedure while obtaining therapeutic effects from NAC.Subtotal stomach-preserving pancreaticoduodenectomy was thenperformed.The operation did not require any unusual techniques and was performed safely.Postoperatively,the patient progressed well,without any ischemic complications.Histopathologically,curative resection was confirmed,and the patient had no recurrence or complications due to ischemia up to six months postoperatively.CONCLUSION Preoperative endovascular stenting,with NAC and DAPT,is effective and safe prior to pancreaticoduodenectomy in potentially resectable pancreatic cancer.

circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

LINC00609 inhibits A549 cells progression through the regulation of miR-128-3p/RND3 axis

Background:Long-chain non-coding RNA(lncRNA)LINC00609 is a potential tumor suppressor,but the mechanism of action in non-small cell lung cancer(NSCLC)is yet to be understood.Objectives:The effects of LINC00609 on A549 cell proliferation,apoptosis,and cell cycle arrest were investigated.Methods:The LINC00609 levels in NSCLC and normal tissues were analyzed by bioinformatics.Expressions of LINC00609,miR-128-3p,and Rho family GTPase 3(RND3)in NSCLC cells(A549)were determined by qRT-PCR.Bioinformatics analysis predicted target genes and dual-luciferase reporter assays to ensure that LINC00609 targeted miR-128-3p and miR-128-3p targeted RND3.The proliferation of cells was determined using EDU and CCK-8.Flow cytometry was used to evaluate cell apoptosis rate and cell cycle.The western blotting assay identified proteins related to proliferation and apoptosis.Results:In NSCLC tissues,LINC00609 was expressed in low levels,while its high expression was associated with a higher survival rate.LINC00609 affected cell proliferation,apoptosis,cell cycle arrest,and expression of related proteins.Dual-luciferase reporter assay showed that LINC00609 binds specifically to miR-128-3p,and miR-128-3p binds to RND3.MiR-128-3p overexpression could neutralize the effects of LINC00609.A siRNA targeting RND3 could reverse the effect of the miR-128-3p inhibitor.Silencing RND3 resulted in a decrease in apoptosis rate and the number of cells in the S-phase and an increase in the number of cells in the G1-phase.Furthermore,phosphorylation levels of the AKT protein and mTOR protein,and Bcl2 expression,increased;however,the expression of RND3,Bax,and caspase3 decreased.Conclusions:LINC00609 regulated miR-128-3p/RND3 axis to modulate A549 cell proliferation,apoptosis,and cell cycle arrest.In the case of NSCLC,LINC00609 could be a potential target for therapy.

The Electric-Field Controllable Non-Volatile 35° Rotation of Magnetic Easy Axis in Magnetoelectric CoFeB/(001)-Cut Pb(Mg_(1/3)Nb_(2/3))O_3-25%PbTiO_3 Heterostructure

Using in situ electric-field-modulated anisotropic magnetoresistance measurement, a large reversible and non- volatile in-plane rotation of magnetic easy axis of -35° between the positive and negative electrical poling states is demonstrated in C040Fe40B20//（001）-cut Pb（Mgl/3Nb2/3）O3-25PbTiO3 （PMN-PT）. The specific magneto- electric coupling mechanism therein is experimentally verified to be related to the synchronous in-plane strain rotation induced by 109° ferroelastic domain switching in the （001）-cut PMN-PT substrate.

Activity of the Fungicide JS399-19 Against Fusarium Head Blight of Wheat and the Risk of Resistance

This report reviews the characteristics of JS399-19, a novel cyanoacrylate fungicide. JS399-19 strongly inhibits the mycelial growth of the fungal plant pathogens of the genus Fusarium and exhibits great potential in controlling Fusarium head blight （FHB） on wheat and other cereals. The mode of action of JS399-19 is evidently different from that of benzimidazole （for example, carbendazim） and other sort of fungicides, making it a possible replacement for carbendazim in China to manage carbendazim-resistant subpopulations of Fusarium graminearum and F. asiaticum. JS399-t9 has excellent protective and curative activity against these pathogens. Incorrect use of this fungicide, however, is likely to select for resistance. Among JS399-19-resistant mutants of F. asiaticum induced in the laboratory, the resistant level of mutants was high and the phenotype of resistance against JS399-19 was conferred by a major gene by genetic analysis. The fitness of laboratory-induced JS399-19-resistant mutants of F. asiaticum was nearly equal to that of their parents. JS399-19 lacks cross resistance with other sort fungicides. To control FHB with JS399-19 and to delay the development of the fungicide-resistance, farmers should use tank mixtures containing JS399-19 and carbendazim, metconazole, tebuconazole, or prothioconazole.

Expression,Purification and Structural Characterization of Mouse Talin-1 Head Δ139-168

Talin-1 head(hereinafter referred to as TH)is the head structure of talin protein,which contains a four-point-one-protein/ezrin/radixin/moesin(FERM)domain.Its F1 domain contains an unstructured loop of 30 amino acids(139-168),which does not interact with other domains.Because TH doesn’t get the crystal structure and whether the unstructured loop has obvious influence on the TH secondary structure,therefore,the truncated talin-1 headΔ139-168(hereinafter referred to as THΔ)was constructed and its structure and the impact of stability after truncation were analyzed.Molecular biology and structural biology methods were used to construct prokaryotic expression vectors of TH and THΔ,explore and optimize the expression conditions of recombinants,and they were purified by affinity chromatography and FPLC gel filtration chromatography.Finally,a large number of stable,high-purity protein samples were prepared successfully.The physicochemical properties and structural stability of the proteins were investigated by dynamic light scattering and circular dichroism.The results showed that the THΔsecondary structure of the truncated body did not change significantly,the structural stability was enhanced and the resistance to guanidine hydrochloride and high temperature was stronger.

The Changes of Baroreflex Sensitivity During Head-up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

Objective To study thechanges of baroreflex sensitivity (BRS) during head - up tilt test (HUT) in patients with vasovagal syncope (VS), and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS. Methods Forty - two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head - up tilt testing, Ante-cubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin , serum nitric oxide (NO), serum NE were measured, the BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results (1) During the syncope, the BRS significantly reduced in HUT(+) group than baseline. At the end of tilt, the level of plasma ET, serum NO in patients with positive HUT significantly increased compared with baseline or normal controls, and the plasma concentration of NE also had the trend of increase. (2) By multiple regression analysis, a significant negative correlation was found between baroreceptor sensitivity and the plasma ET, NO at the end of HUT in patients with positive HUT, but there was no relationship between BRS and NE. Conclusions During the syncope occure, the BRS in patients with VS decreased significantly compared with normal controls. The abnormal plasma ET, NO concen-tration might contribute to the mechanism of VS.

C1-2哑铃型肿瘤的手术治疗

目的：研究C1-2哑铃型肿瘤的手术方式以及手术对颈椎稳定性的影响。方法：回顾分析北京大学第三医院神经外科2007年1月至2010年7月收治的C1-2哑铃型肿瘤手术病例共16例,根据肿瘤的大小和侵及范围选择不同手术方式切除肿瘤。常规病人先行俯卧位,首先行后正中半椎板入路切除椎管内外肿瘤,充分显露肿瘤后,切除硬膜外部分,待有足够空间,再切除硬膜下部分;如果肿瘤在椎管内部分超过椎管的一半以上,则须切除部分C1-2棘突基底以利显露手术区域,以防脊髓损伤。硬膜如有缺损则需修补,肌肉缝合要做到解剖复位,以利颈椎的稳定性;如果肿瘤侵及椎管外超过4 cm或完全包绕椎动脉Ⅰ期手术无法全切,则需再联合侧方入路切除肿瘤。结果：共治疗C1-2哑铃型肿瘤16例,其中神经鞘瘤12例,脊膜瘤3例,神经节细胞瘤1例;全切除14例,次全切除2例。病人术后颈部疼痛、上肢肌肉无力等症状均有明显缓解。术后随访348个月,未出现颈椎不稳定和肿瘤复发。结论：后正中半椎板入路或联合侧方入路能较好地切除C1-2哑铃型肿瘤,同时能较好地保持颈椎的稳定性。

短链脂肪酸-酰化淀粉对小鼠抑郁样行为的缓解及机制

大量研究证实“微生物-肠-脑轴”在抑郁症的发生发展中发挥重要作用,而肠道微生物产生的短链脂肪酸(short chain fatty acids,SCFAs),更是参与神经调控作用的关键分子。该研究首次采用SCFA-酰化淀粉在大肠定点释放5类短链脂肪酸,探究其对慢性应激诱导的抑郁症状的缓解及机制。以雄性C57BL/6 J小鼠为研究对象,通过为期5周的慢性不可预知温和应激构建抑郁小鼠模型,通过旷场实验、高架十字迷宫实验和强迫游泳实验对小鼠的抑郁样行为进行评价。同时对小鼠应激激素、神经递质水平及相关酶的表达水平进行检测。结果显示,乙酸、异丁酸和丁酸能在不同程度上减轻小鼠抑郁样行为,其可能机制与SCFAs修复下丘脑-垂体-肾上腺轴反馈调节障碍、恢复5-羟色胺的正常代谢相关。该研究为抑郁症的营养干预提供了新的理论依据。

福建姜黄挥发油化学成分的HS-SPME-GC-MS分析

采用水蒸气蒸馏法提取福建姜黄挥发油,应用顶空固相微萃取进样结合气相色谱-串联质谱联用技术(HS-SPME-GC-MS)分析姜黄挥发油的化学成分。结果表明:姜黄挥发油含有量为7.2%(mL/g),从姜黄挥发油中共分出62个色谱峰,初步鉴定出了其中的51种化学成分,占总挥发油总量的98.41%。在鉴定的化合物中,主要为单萜类化合物和倍半萜类化合物,其中新发现一种主要成分为β-柏木烯,相对含量占比高达26.58%,这可作为福建姜黄挥发油的特征成分和主要品质指标。本研究结果将为福建姜黄植物药材的品质评价提供科学依据。

Preoperative defining system for pancreatic head cancer considering surgical resection

AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing “resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly”. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size ≥ 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 ≥ 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.

颅脑放疗中保护下丘脑-垂体轴功能的意义及研究现状

放射治疗是绝大多数颅脑及头颈部肿瘤治疗的重要手段之一,对提高患者的生存率、减少局部复发及改善疾病症状有不可替代的作用。然而,颅脑放疗后可能会出现不同程度的不良反应,其中以下丘脑-垂体(the hypothalamo-pituitary,HT-P)轴相关内分泌功能障碍较为常见。本文通过文献复习阐明放疗引起HT-P相关神经内分泌功能障碍的影响因素、病理机制及筛查手段,从而强调在颅脑放疗中下丘脑-垂体功能保护的重要性。同时,对比不同放疗技术在颅脑放疗中实现保护下丘脑-垂体功能的应用现状,由此展望未来该领域研究方向。

Shock index and its variants as predictors of mortality in severe traumatic brain injury

BACKGROUND The increase in severe traumatic brain injury(sTBI)incidence is a worldwide phenomenon,resulting in a heavy disease burden in the public health systems,specifically in emerging countries.The shock index(SI)is a physiological parameter that indicates cardiovascular status and has been used as a tool to assess the presence and severity of shock,which is increased in sTBI.Considering the high mortality of sTBI,scrutinizing the predictive potential of SI and its variants is vital.AIM To describe the predictive potential of SI and its variants in sTBI.METHODS This study included 71 patients(61 men and 10 women)divided into two groups:Survival(S;n=49)and Non-survival(NS;n=22).The responses of blood pressure and heart rate(HR)were collected at admission and 48 h after admission.The SI,reverse SI(rSI),rSI multiplied by the Glasgow Coma Score(rSIG),and Age multiplied SI(AgeSI)were calculated.Group comparisons included Shapiro-Wilk tests,and independent samples t-tests.For predictive analysis,logistic regression,receiver operator curves(ROC)curves,and area under the curve(AUC)measurements were performed.RESULTS No significant differences between groups were identified for SI,rSI,or rSIG.The AgeSI was significantly higher in NS patients at 48 h following admission(S:26.32±14.2,and NS:37.27±17.8;P=0.016).Both the logistic regression and the AUC following ROC curve analysis showed that only AgeSI at 48 h was capable of predicting sTBI outcomes.CONCLUSION Although an altered balance between HR and blood pressure can provide insights into the adequacy of oxygen delivery to tissues and the overall cardiac function,only the AgeSI was a viable outcome-predictive tool in sTBI,warranting future research in different cohorts.

基于RANKL/RANK/OPG信号轴探讨骨痹通消颗粒对激素性股骨头坏死模型小鼠的治疗作用

目的观察骨痹通消颗粒对激素性股骨头坏死模型小鼠的治疗作用,并从核因子-κB受体活化因子配体/核因子-κB受体活化因子/骨保护素(RANKL/RANK/OPG)信号轴探讨其作用机制。方法采取腹腔注射脂多糖和臀肌注射醋酸泼尼松龙复制激素性股骨头缺血坏死(SONFH)动物模型,经核磁共振鉴定后,将模型复制成功的60只小鼠分成模型(MC)组、骨痹通消颗粒(GBTX)组及通络生骨胶囊(PC)组,每组20只,另设12只正常小鼠作为空白对照(NC)组。分别予以对应组灌胃相应药物12周后麻醉状态下取材,观察各组小鼠治疗前后的一般行为;酶联免疫吸附试验(ELISA)检测各组小鼠的骨碱性磷酸酶(BALP)和I型氨基端延长肽(PINP)含量;Western blotting和实时荧光定量聚合酶链反应(qRT-qPCR)检测各组RANK、RANKL、OPG、磷脂酰肌醇特异性磷脂酶Cγ2(PLCγ2)、组织蛋白酶K(CTSK)、抗酒石酸酸性磷酸酶(TRAP)的蛋白和基因表达。结果核磁共振显示,模型复制成功后的小鼠左侧髋部呈高信号状态。与NC组比较,MC组BALP、PINP水平,以及OPG蛋白和基因相对表达量均降低(P<0.05),RANK、RANKL、PLCγ2、CTSK、TRAP蛋白和基因相对表达量均升高(P<0.05);与MC组比较,GBTX组和PC组BALP、PINP水平,以及OPG蛋白和基因相对表达量均升高(P<0.05),RANK、RANKL、PLCγ2、CTSK、TRAP蛋白和基因相对表达量均下降(P<0.05);与GBTX组比较,PC组OPG、RANK、RANKL、CTSK、TRAP蛋白和基因相对表达量,以及PLCγ2蛋白相对表达量差异均无统计学意义(P>0.05),而PC组PLCγ2基因相对表达量较GBTX组下降(P<0.05)。结论骨痹通消颗粒可能通过上调OPG表达,抑制RANK、RANKL、PLCγ2、CTSK和TRAP表达,从而改善股骨头坏死情况。

轻小型高精度机载稳定云台设计与研究

为降低无人机在飞行过程中的抖动对图像采集造成的极大影响,设计了一款轻小型、高精度、大负载的三轴云台。从稳定云台的结构设计、静力学仿真、动力学仿真、样机组装、挂飞试验等方面进行了全流程研究,为机载稳定云台的研发提供了系统的研究方法,具有重要的参考价值。

三孔式纵轴截割头的研制

作为煤矿采掘机械中破岩落煤的核心部件,悬臂式掘进机截割头的联接方式分为平键联接、花键联接、方孔联接等。针对单孔式花键联接截割头存在的联接牢固性差、截割头大端处易磨损及截割头内部易进煤尘等问题,研制了三孔式纵轴截割头。采用最佳稳定性的三孔式联接、新型耐磨块结构及可拆卸式半环的防尘装置,提高了截割头的截割效率和使用寿命,在煤岩截割过程中具备较高的可靠性和稳定性。为纵轴式截割头的研发提供了一种思路和参考,具有一定的实用和推广价值。

基于PowerInspect五轴在机检测(OMV)的运用研究

本研究项目探讨了如何实现工艺和质量控制自动化,基于数控加工质量控制缺环的解决。在机检测技术(OMV)作为先进的数控加工质量控制技术,可以直接在机床上对工件进行检测,获取定位数据,并根据零件当前状态调整加工程序。这种技术可以大大提高生产自动化能力,减少人工干预和错误率,提高生产效率和产品质量。对于复杂、无传统找正特征的零件,自适应加工技术具有显著优势。

一种面向门窗加工的四轴机头加工机构研究

随着现代建筑业的迅猛发展,门窗加工的精度与效率要求不断提高,传统的三轴加工设备已经不能完全满足行业对复杂造型和高精度门窗的制作需求。围绕一种新型的四轴机头加工机构进行研究,通过技术革新提高门窗加工的自动化和智能化水平。文章详细分析了四轴机头加工机构的技术特点,探讨其结构设计、控制系统及性能优势,并针对现有技术的局限性提出改进措施。通过实际的性能测试,验证了该机构在门窗加工中的应用潜力和实际效益。

航向测量系统中三轴磁传感器标定的等效两步法

针对航向测量系统中三轴磁传感器误差参数标定问题提出了等效两步法。通过奇异值分解将测量模型等效为一组坐标变换,分析误差参数的几何意义及等效变换方法的意义与特点,依据几何意义将标定过程分为两步进行,即等效传感器坐标系标定及等效非对准标定。利用椭球面方程系数计算等效传感器坐标系误差参数,明确椭球法标定参数的几何意义;应用主成分分析法进行等效非对准标定,分析传统主成分分析法产生符号错误及非正交问题的原因与影响,并研究符号修正与正交修正方法。等效两步法的标定过程不需要航姿参考、地磁信息及辅助传感器,实验表明其航向角校正精度与点积不变法相当。