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.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

Black Hole Complementarity in Terms of the Outsider and Insider Perspectives

A complementarity hypothesis concerning outsider and insider perspectives of a gargantuan black hole is proposed. The two thought experiments presented herein are followed by a brief discussion of a new interpretation of black hole interior “space-and-time-reversal”. Specifically, it is proposed that the “singularity” space of the black hole interior is time-like and the expansion time of the black hole interior is space-like. The resemblance of this new insider interpretation to our own expanding and redshifting big bang universe is compelling.

血清抗PLA2R抗体、增殖诱导配体、24 h尿蛋白水平联合检测在特发性膜性肾病中的应用价值

目的:探究在特发性膜性肾病中采用血清抗PLA2R抗体、增殖诱导配体(APRIL)、24 h尿蛋白水平联合检测的应用价值。方法:研究对象为80例特发性膜性肾病患者与30例进行体检健康者。回顾80例患者的病历资料,所有患者的病情均经肾穿刺活检病理检查确诊,并按病理分期分为3组,即病理分期为1期者为观察A组(25例),病理分期为2期者为观察B组(30例),病理分期为3期者为观察C组(25例),健康体检者为对照组。四组参与研究者,均开展血清抗PLA2R抗体、增殖诱导配体(APRIL)、24 h尿蛋白水平检测,对比四组血清抗PLA2R抗体、增殖诱导配体(APRIL)、24 h尿蛋白水平,同时评估联合检测在特发性膜性肾病中的应用价值。结果:特发性膜性肾病患者的抗PLA2R抗体、APRIL、24 h尿蛋白水平明显高于对照组相应指标水平,比较差异具有统计学意义(均P<0.05);三组患者的血清抗PLA2R抗体、APRIL、24 h尿蛋白水平比较差异无统计学意义(均P>0.05),其中观察C组患者以上指标高于观察1、2组,观察B组患者以上指标高于观察A组,比较差异均具有统计学意义(均P<0.05);血清抗PLA2R抗体表达越高,患者的APRIL、24 h尿蛋白水平越高,之间存在明显的正相关关系,比较差异具有统计学意义(均P<0.05)。结论:特发性膜性肾病采用血清抗PLA2R抗体、增殖诱导配体(APRIL)、24 h尿蛋白水平联合检测,不仅可以检测出相关病情,还可以对病情的严重程度进行鉴别诊断。

(R)-3-氨基-3,4-二氢-1-甲氧基喹啉-2(1H)-酮的合成

首先,以D-苯丙氨酸和二碳酸二叔丁酯为起始原料,经过Boc氨基保护合成N-叔丁氧羰基苯丙氨酸;然后N-叔丁氧羰基苯丙氨酸在甲氧氨盐酸盐的作用下生成缩合物2-(N-叔丁氧羰基)-N-甲氧基-3-苯丙酰胺;然后缩合物在催化剂二(三氟乙酸)碘苯的作用下成环生成3-(N-叔丁氧羰基)-3,4-二氢-1-甲氧基喹啉-2(1H)-酮;最后后者经过脱保护合成目标产物。该方法具有操作简单、成本低等优点,四步总收率15.1%,产物经过1H-NMR和MS确认。

H240R和MGF505-7R基因缺失非洲猪瘟病毒的构建及其生长特性的初步研究

为探究H240R和MGF505-7R基因对非洲猪瘟病毒(ASFV)复制水平的影响,本研究采用PCR扩增ASFV HLJ/18株H240R基因和MGF505-7R基因阅读框前后各1000 bp的同源臂,分别克隆至pBS-EGFP及pBS-Mcherry载体中,构建同源臂质粒pBS-GFP-H240R和pBS-Mcherry-MGF505-7R,采用PCR和测序鉴定正确。根据CRISPR/Cas9系统sgRNA设计原则设计分别靶向H240R和MGF505-7R基因的小向导RNA(sgRNA),并克隆至pX330载体中,构建重组质粒pX330-sgH240R和pX330-sgMGF505-7R,经测序鉴定正确后,将线性化的同源臂质粒pBS-GFP-H240R与pX330-sgH240R共转染猪肺泡巨噬细胞(PAM),再以ASFV感染,通过观察荧光并采用噬斑筛选纯化,构建H240R基因缺失病毒ASFV-ΔH240R;采用上述类似的方式构建MGF505-7R基因缺失病毒ASFV-Δ7R;在ASFV-ΔH240R的基础上,将线性化的同源臂质粒pBS-Mcherry-MGF505-7R与pX330-sgMGF505-7R共转染PAM后,再以ASFV-ΔH240R感染,通过观察荧光并采用噬斑筛选纯化,构建双基因缺失病毒ASFV-ΔH240R-Δ7R。上述3株基因缺失病毒均采用PCR和测序鉴定正确后,均以MOI 1感染PAM,24 h后于荧光显微镜观察;同时采用红细胞吸附试验测定不同培养时间的病毒载量即半数红细胞吸附量(HAD50),并绘制各病毒的生长曲线。结果显示,ASFV-ΔH240R、ASFV-Δ7R及ASFV-ΔH240R-Δ7R感染的PAM分别出现绿色荧光、红色荧光及红绿色双色荧光,而ASFV-WT感染的细胞无荧光,表明正确构建各基因缺失病毒。生长曲线测定结果显示,ASFV-Δ7R和亲本病毒生长曲线基本一致,ASFV-ΔH240R复制水平显著低于亲本病毒(P<0.001),ASFV-ΔH240R-Δ7R复制水平显著高于ASFV-ΔH240R(P<0.01),但仍低于亲本株。表明MGF505-7R基因与病毒的复制无关,但H240R基因与病毒的复制有关,在ASFV-ΔH240R的基础上缺失MGF505-7R基因则可部分恢复病毒的复制能力。本研究构建了3株基因缺失ASFV并测定其生长曲线,为进一步研究ASFV基因功能提供了数据参考。

H型高血压合并急性心肌梗死患者外周血Furin、sTWEAK、NLR与心肌损伤指标和预后不良的关系

目的分析H型高血压(HHT)合并急性心肌梗死(AMI)患者外周血弗林蛋白酶(Furin)、可溶性肿瘤坏死因子样凋亡弱诱导因子(sTWEAK)、中性粒细胞/淋巴细胞比值(NLR)与心肌损伤指标和预后不良的关系。方法选取2019年1月—2021年2月北京中医药大学房山医院心血管科收治的HHT合并AMI患者231例为HHT+AMI组,单纯HHT患者77例为HHT组,医院健康体检者52例为健康对照组。比较3组受试者外周血Furin、sTWEAK、NLR及血清心肌损伤指标[肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、N末端脑钠肽前体(NT-proBNP)],并分析外周血Furin、sTWEAK、NLR与心肌损伤指标的相关性。随访1年统计HHT+AMI组患者主要不良心血管事件(MACE)发生情况,采用Logistic回归分析HHT合并AMI患者发生MACE的影响因素,绘制受试者工作特征曲线(ROC)分析三者对HHT合并AMI患者发生MACE的预测价值。结果外周血Furin、sTWEAK、NLR水平比较,HHT+AMI组>HHT组>健康对照组(F/P=981.029/<0.001、1032.486/<0.001、326.617/<0.001),MACE亚组高于非MACE亚组(t/P=19.498/<0.001、17.909/<0.001、2.507/<0.001);HHT+AMI组CK-MB水平高于HHT组和健康对照组,血清cTnI、NT-proBNP水平比较,HHT+AMI组>HHT组>健康对照组(F/P=580.966/<0.001、672.830/<0.001、463.233/<0.001);外周血Furin、sTWEAK、NLR与血清CK-MB、cTnI、NT-proBNP水平均呈显著正相关(Furin:r/P=0.713/<0.001、0.604/<0.001、0.515/<0.001;sTWEAK:r/P=0.412/0.002、0.533/<0.001、0.502/<0.001;NLR:r/P=0.513/<0.001、0.554/<0.001、0.481/<0.001);KillipⅢ/Ⅳ级、Gensini评分高、Furin高、sTWEAK高、NLR高均是导致HHT合并AMI患者MACE发生的独立危险因素[OR(95%CI)=1.725(1.178~2.524)、1.571(1.160~2.128)、2.412(1.527~3.806)、2.204(1.421~3.418)、1.784(1.213~2.624)]。外周血Furin、sTWEAK、NLR及三者联合检测预测HHT合并AMI患者发生MACE的曲线下面积(AUC)分别为0.740、0.715、0.693、0.841,三指标联合预测效能优于各指标单独检测(Z/P=2.038/0.042、2.459/0.014、4.037/<0.001)。结论Furin、sTWEAK、NLR在HHT合并AMI患者外周血中均异常升高,且与心肌损伤、预后不良关系密切,三者联合检测可作为预测HHT合并AMI患者预后不良的参考依据。

Resuscitation therapy for traumatic brain injuryinduced coma in rats:mechanisms of median nerve electrical stimulation

In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually in-creased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our ifndings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the pre-frontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

Dephosphorylation of cardiomyocyte Cx43 is associated with myocardial ischemia and reperfusion injury

Objective：Myocardial ischemia/reperfusion（I/R） injury is the leading cause of death in the world. However, the details of the mechanism of its pathophysiology are still unknown. The present study was designed to investigate the role of connexin 43（Cx43） in acute models of myocardial I/R injury. Methods： Male C57BL/6 mice were subjected to myocardial ischemia（45 min） followed by reperfusion（4 hrs） in vivo. The whole operation was monitored using a two-lead ECG. Hearts were harvested and the level of protein was assessed by western blot analysis. Haematoxylin and Eosin（HE） staining was used to detect the extent of neutrophil infiltration. The expression level of IL-6 was detected by ELISA. Results： A murine myocardial I/R injury model was constructed successfully. Phosphorylated Cx43 decreased 83. 45% while non-phosphorylated Cx43 increased 1.62- fold in the myocardium after I/R injury. Neutrophil infiltration and the expression of the inflammatory cytokine IL-6 increased in the myocardium following I/R. Conclusion： During myocardial I/R injury, cardiomyocyte Cx43 is dephosphorylated, and this may be associated with an inflammatory response.

Mediated protective effect of electroacupuncture pretreatment by miR-214 on myocardial ischemia/reperfusion injury

BackgroundElectroacupuncture 预告的处理在损害和 microRNAs (miRNAs ) 能在心脏的功能的各种各样的方面上扮演的心肌的 ischemia/reperfusion (I/R ) 起一个保护的作用。然而，在由心肌的 I/R 损害上的 electroacupuncture 预告的处理的 cardioprotection 的 miRNAs 的角色仍然保持未知。学习的目的是检验 miR-214 是否被 electroacupuncture.MethodsUsing 老鼠涉及 cardioprotection 心肌的 I/R 模型，我们在心肌的 I/R 损害检验了 electroacupuncture 预告的处理的角色并且在 miR-214 的表示分析了变化。另外， I/R 被在 I/R 损害上在 electroacupuncture 预告的处理的 H9c2 房间文化，和效果上执行氧葡萄糖剥夺(OGD ) 在 vitro 模仿以及 miR-214 的表现水平在 vitro 被检验。而且， miR-214 模仿是进 对待OGD 的 H9c2 房间的 transfected ，我们分析了房间 apoptosis ，喂奶脱氢酶( LDH )和肌酸 kinase ( CK )活动，细胞内部的免费 Ca 2+集中([ Ca 2+]i)以及钠/钙 exchanger 的相对蛋白质层次 1 ( NCX1 )，象BCL2一样 11 ( BIM )，calmodulin依赖的蛋白质 kinase IIδ ；( CaMKIIδ ；)并且在 vivo 结果的 Cyclophilin D ( CypD ) .ResultsThe 表明与 I/R 组相比， electroacupuncture 预告的处理组显示出重要减少的心肌的梗塞尺寸，以及心脏的功能的增加的索引包括心率，意味着动脉的压力， left ；为左室的压力升起并且衰退的室的收缩压力和最大的率( ± ； dp/dt 最大)。另外， electroacupuncture 预告的处理能禁止 I/R 损害导致的 LDH 和 CK 活动的举起。量的 PCR (qPCR ) 结果证明 electroacupuncture 预告的处理能在老鼠对心肌的 I/R 损害向 cardioprotection 提供 miR-214 起来规定。在 vitro，同时， electroacupuncture 预告的处理保护了 H9c2 房间免于导致 OGD 的损害。miR-214 的 Transfection 由减少 apoptosis，减少的 LDH 和 CK 活动在对 H9c2 房间的导致 OGD 的损害上模仿显示出的保护的效果，导致 OGD 的 Ca 2+ 和下面调整的提高的蛋白质 NCX1 铺平的 rescuing， BIM， CaMKIIδ；并且 CypD.ConclusionsOur 调查结果第一证明那个 electroacupuncture 预告的处理在心肌的 I/R 损害支持 miR-214 的表示， miR-214 在心肌的 I/R 损害上贡献 electroacupuncture 的保护的效果。

Cardioprotective effects of Guanxinshutong （GXST） against myocardial ischemia/ reperfusion injury in rats

对 cardioprotective 药的灌注损害的 BackgroundThe 保护的效果最近被评估了并且发现了不适当。Guanxinshutong (GXST ) ，传统的植物的联合和蒙古的药，在在临床的试用对待心绞痛有效、安全。我们在老鼠对心肌的局部缺血和灌注(MI/R ) 损害估计 GXST 的 cardioprotective 效果并且探索它的可能的 mechanism.MethodsForty -- 五只男 Sprague Dawley 老鼠被使随机化进三个组：non-MI/R 组(假冒， n = 15 ) ，与车辆对待的 MI/R 组(控制， n = 15 ) 并且与 GXST 对待的 MI/R 组(药， n = 15 ) 。MI/R 被左前面的下降冠的动脉(男孩) 的结扎导致 30 分钟，在控制和药组由 2/24 小时灌注列在后面。在假冒的组，没有吸藏， LAD 被暴露。GXST 粉末(在药组) 或盐(在控制和假冒的组) 在外科以前从 7 白天经由直接胃的 gavage 被管理。血样品从颈动脉动脉被收集(10 只老鼠各组织) 在 2 小时灌注以后，决定肿瘤坏死 factor-&#x003b1 的层次；(TNF-&#x003b1；) ， interleukin-1&#x003b2；(IL-1&#x003b2；) ， interleukin-6 (IL-6 ) 和用连接酶的 immunosorbent 试金的细胞间的粘附 molecule-1 (ICAM-1 ) 。动物然后被牺牲，心为组织病理学说和西方的污点分析被收获。梗塞尺寸在留下被测量在在 24 小时 reperfusion.ResultsGXST 以后的每个组的五只老鼠显著地减少了 TNF-&#x003b1 的层次；， IL-1&#x003b2；， IL-6， ICAM-1， apoptosis 索引(AI ) 和梗塞缩放。GXST 显然也禁止了原子因素 kappa B (NF-&#x003ba； B ) 活动什么时候与控制组相比(所有 P &#x0003c；0.05 ).ConclusionsGXST 在在老鼠保护心肌层免于 MI/R 损害是有效的。它的可能的 cardioprotective 机制包含煽动性的反应和 apoptosis 追随者 MI/R 损害的抑制。

Swine-origin influenza-virus-induced acute lung injury:Novel or classical pathogenesis?

Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia.Due to their hostrange diversity,genetic and antigenic diversity,and potential to reassort genetically in vivo,influenza A viruses are continual sources of novel influenza strains that lead to the emergence of periodic epidemics and outbreaks in humans.Thus,newly emerging viral diseases are always major threats to public health.In March 2009,a novel influenza virus suddenly emerged and caused a worldwide pandemic.The novel pandemic influenza virus was genetically and antigenically distinct from previous seasonal human influenza A/H1N1 viruses;it was identified to have originated from pigs,and further genetic analysis revealed it as a subtype of A/H1N1,thus later called a swine-origin influenza virus A/H1N1.Since the novel virus emerged,epidemiological surveys and research on experimental animal models have been conducted,and characteristics of the novel influenza virus have been determined but the exact mechanisms of pulmonary pathogenesis remain to be elucidated.In this editorial,we summa-rize and discuss the recent pandemic caused by the novel swine-origin influenza virus A/H1N1 with a focus on the mechanism of pathogenesis to obtain an insight into potential therapeutic strategies.

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.

Ischemia-reperfusion Injury Up-regulates Pim-3 Gene Expression in Myocardial Tissue

This study examined the effect of ischemia-reperfusion injury on the expression of Pim-3 gene in myocardial tissues and their underlying mechanism.Rat models of myocardial ischemia-reperfusion injury were established by ligating the left anterior descending coronary artery of the rats.A total of 30 SD male adult rats were randomly divided into 5 groups:group A (sham operation,n=6);group B (in which the rats were subjected to 15 min of ischemia by ligation of the left anterior descending coronary artery,n=6);group C (in which the rats received 30 min of ischemia,n=6),group D and group E (in which the left anterior descending coronary artery of the rats were ligated for 30 min and then reperfused for 30 min or 120 min,n=6 in each).The left ventricular tissues were removed immediately after the ischemia-reperfusion injury.Neonatal cardiomyocytes were cultured and treated with different concentrations of H 2 O 2 (0,5,10,20 μmol/L) or tumor necrosis factor-α (TNF-α,0,1,5,10 ng/mL).The mRNA and protein expression of Pim-3 gene was determined by using RT-PCR,western blotting and immunohistochemistry.Additionally,neonatal cardiomyocytes were transfected with Pim-3 siRNA,and induced to develop apoptosis by using H 2 O 2.The results showed that normal myocardial tissues expressed a quantity of Pim-3 gene mRNA and protein.Ischemia-reperfusion injury could up-regulate the mRNA and protein expression of Pim-3 gene in myocardial tissues.Furthermore,H 2 O 2 but not TNF-α up-regulated the Pim-3 gene expression in cultured cardiomyocytes.And Pim-3 silencing failed to strengthen the H 2 O 2-inducing apoptosis in cardiomyocytes.It was concluded that ischemia-reperfusion injury up-regulated the Pim-3 gene expression through oxidative stress signaling pathway in myocardial tissues.

Intestinal microflora in rats with ischemia/reperfusion liver injury

Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

保肝药物在2H3R3Z3E3(S3)/4H3R3方案抗结核治疗肺结核致肝损伤患者的效果分析

目的分析益肝灵软胶囊在2H3R3Z3E3(S3)/4H3R3方案抗结核治疗肺结核致肝损伤患者的效果。方法选取2019年1月至2022年12月我院收治的肺结核患者106例,分为对照组和研究组各53例。所有患者均行2H3R3Z3E3(S3)/4H3R3方案抗结核治疗,在此基础上对照组给予复方甘草酸苷片治疗,研究组给予益肝灵软胶囊治疗。对比两组肝损伤发生率,对比两组肝功能指标、免疫指标,对比两组不良反应发生率和治疗有效率。结果研究组肝损伤发生率低于对照组(P<0.05);研究组ALB、ALT、AST、TP以及IgA、IgM、IgG均低于对照组(P<0.05);研究组不良反应发生率低于对照组(P<0.05);研究组总有效率显著高于对照组(P<0.05)。结论采用益肝灵软胶囊治疗2H3R3Z3E3(S3)/4H3R3方案抗结核治疗肺结核致肝损伤患者,可降低肝损伤发生率,改善肝功能与免疫指标,减少不良反应,提高临床疗效。

Effects of prostaglandin E combined with continuous renal replacement therapy on septic acute kidney injury

BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.

Identification of key genes involved in recovery from spinal cord injury in adult zebrafish

Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord injury.The subacute phase after spinal cord injury is critical to the recovery of neurological function,which involves tissue bridging and axon regeneration.In this study,we found that zebrafish spontaneously recovered 44%of their swimming ability within the subacute phase(2 weeks)after spinal cord injury.During this period,we identified 7762 differentially expressed genes in spinal cord tissue:2950 were up-regulated and 4812 were down-regulated.These differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain,axon regeneration,and cell-component morphogenesis.The genes were also mostly involved in the regulation of metabolic pathways,the cell cycle,and gene-regulation pathways.We verified the gene expression of two differentially expressed genes,clasp2 up-regulation and h1m down-regulation,in zebrafish spinal cord tissue in vitro.Pathway enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein,which is responsible for axon extension regulated by microtubules.Down-regulated h1m controls endogenous stem cell differentiation after spinal cord injury.This study provides new candidate genes,clasp2 and h1m,as potential therapeutic intervention targets for spinal cord injury repair by neuroregeneration.All experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical&Pharmaceutical Sciences(approval No.IMPS-EAEP-Q-2019-02)on September 24,2019.

回热器对CO_(2)/R32热泵热水器性能的影响——基于窄点温差分析法

当今,生活热水所消耗的能源越来越多,热泵热水器由于具有显著的节能作用,被广泛应用于热水生产。自然工质CO_(2)较低的临界温度使其容易实现跨临界循环,将其应用于热泵热水器系统中更接近于Lorentz循环,可获得更优的热力学性能。但是,CO_(2)系统还存在着效率较低及运行压力较高的劣势,采用混合工质代替纯质CO_(2)是一种理想的解决方案。尝试用CO_(2)/R32混合制冷剂替代纯质CO_(2)应用于热泵热水器系统,建立相关热力学模型,基于窄点温差分析法,讨论不同组分配比条件下,有、无回热器的系统综合性能并进行详细对比。结果表明,CO_(2)/R32混合制冷剂的最优组分配比为0.84/0.16;回热器对系统热力学完善度提升的幅度很小,最大不超过1.8%,建议系统不采用回热器;CO_(2)/R32可将纯质CO_(2)系统和纯质R32系统的COP h分别提升6.2%和5.7%,还能将CO_(2)系统的运行高压降低13.6%。