Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

The Research on Death in King Lear

As one masterpiece by Shakespeare,King Lear has been aroused a hot argument about its miserable ending since it come out to press.This paper will take this controversial ending as the starting point,focus on the seemingly unfair ending of Lear and Cordelia’s tragic death and making a thorough textual study on its death theme.By a systematic and comprehensive analysis of the ending,I attempt to reveal the deep-seated significance behind the characters’forlorn death.The death of Lear and Cordelia are not the absence of“poetic justice”,but an elaborate arrangement by Shakespeare.With the death of a series of characters,the playwright expresses his own understanding on human existence.Shakespeare clearly makes his choice and assents the kindness of human nature.

An Analysis of Interpersonal Function of the Dialogues in the Film The King's Speech

Based on the framework of Halliday's theory of interpersonal function, this study intends to analyze the dialogues in the film The King's Speech from the three aspects of mood type, modal operator and vocative address by adopting both quantitative and qualitative methods. The significances of successful realizations of interpersonal function to the role characterization, plot development and thematic construction in the film are also demonstrated, thus deepening the understanding and appreciation of the film.

基于King达标理论的培训方案对临床护士叙事能力及人文关怀能力的影响

目的:探讨基于King达标理论构建临床护士叙事护理培训方案对临床护士叙事护理能力、人文关怀能力及共情能力的影响。方法:2023年3月—5月选取淄博市某三级甲等医院138名护士,采用随机数字表法分为试验组和对照组。对照组实施常规叙事护理培训,试验组在对照组的基础上实施基于King达标理论指导下的叙事护理方案。采用医学叙事能力量表(NCS)、关怀能力评价量表(CAI)、杰弗逊共情量表(JSE-HP)进行效果评价。结果:干预后,试验组护士NCS、CAI及JSE-HP得分均高于对照组,差异均有统计学意义(P<0.05)。结论:基于King达标理论构建的临床护士叙事培训方案可有效提高临床护士叙事护理能力、促进人文关怀能力并提升护士共情能力。

S-烯丙基巯基半胱氨酸促进CD8+T细胞杀伤功能的机制研究

目的探究S-烯丙基巯基半胱氨酸(S-allylmercaptocysteine,SAMC)对CD8^(+)T细胞杀伤鼻咽癌细胞功能的影响及机制。方法将人鼻咽癌细胞HK-1和C666-1与SAMC共培养,分为0、25、50、100μmol/L SAMC组,Western blot检测肿瘤细胞程序性死亡配体-1(programmed cell death-ligand 1,PD-L1)表达。CD8^(+)T细胞分别与HK-1和C666-1细胞以10∶1的比例共培养并加入0、25、50、100μmol/L SAMC,检测CD8^(+)T对HK-1和C666-1的杀伤能力,酶联免疫法(ELISA)检测干扰素(INF-γ)和肿瘤坏死因子-α(TNF-α)浓度,构建鼻咽细胞HK-1的小鼠皮下移植瘤模型,分为对照组、CD8^(+)T细胞组、SAMC组、SAMC+CD8^(+)T细胞组,各组小鼠治疗期间测量瘤体积,治疗结束后取小鼠肿瘤组织,Western blot检测肿瘤组织中PD-L1表达,ELISA检测小鼠血清INF-γ和TNF-α浓度。结果相比于0μmol/L SAMC组,25、50、100μmol/L SAMC组HK-1和C666-1细胞PD-L1表达均显著下调(P<0.05),相比于0μmol/L SAMC+CD8^(+)T细胞组,25、50、100μmol/L SAMC+CD8^(+)T细胞组HK-1和C666-1细胞培养上清中INF-γ和TNF-α浓度均能显著增加,HK-1和C666-1细胞裂解率显著增加(P<0.01)。相比于对照组,CD8^(+)T细胞组和SAMC+CD8^(+)T细胞组小鼠瘤体积和瘤重显著下降(P<0.05),小鼠血清INF-γ和TNF-α浓度显著增加,相比于CD8^(+)T细胞组,SAMC+CD8^(+)T细胞组小鼠瘤体积和瘤重显著下降(P<0.05),小鼠血清INF-γ和TNF-α浓度显著增加(P<0.05),肿瘤组织PD-L1表达显著下调(P<0.01)。结论SAMC可通过抑制人鼻咽癌细胞PD-L1表达而促进CD8^(+)T细胞的杀伤功能。

基于MRI影像组学构建PD-1/PD-L1抑制剂治疗dMMR/MSI-H直肠癌疗效的预测模型

目的:探讨MRI影像组学模型在程序性细胞死亡蛋白-1(PD-1)/程序性细胞死亡-配体1(PD-L1)抑制剂联合全程新辅助治疗(TNT)局部进展期直肠癌(LARC)的疗效预测价值。方法:收集河南中医药大学第一附属医院PD-1/PD-L1抑制剂联合TNT治疗的80例错配修复基因缺陷(dMMR)/微卫星高度不稳定(MSI-H)基因型中低位LARC患者的临床和影像资料。将入组患者按7∶3比例分为训练集和测试集,提取影像组学特征,从中筛选并构建影像组学模型。描绘影像组学模型的Rad-score与病理金标准之间的受试者工作特征(ROC)曲线,计算曲线下面积(AUC),并评价模型的诊断效能。采用决策曲线分析(DCA)计算风险阈值的范围,并评估临床获益情况。收集湖南省人民医院25例dMMR/MSI-H基因型LARC患者的影像资料作为外部验证集。结果:训练集、测试集及外部验证集三者之间的临床特征无统计学差异(P>0.05)。经过降维处理、t检验及一致性检验以及LASSO交叉验证后,筛选出一阶偏度特征和体积2个特征构建影像组学模型。训练集、测试集和外部验证集的影像组学预测模型ROC曲线的AUC、灵敏度、特异度、阳性预测值和阴性预测值分别为0.920、97.1%、85.7%、91.9%、94.7%;0.885、80.0%、88.9%、92.3%、72.7%;0.875、87.5%、88.9%、93.3%、80.0%。DCA曲线显示,当风险阈值范围为0%~82%时,采用影像组学模型预测LARC患者为病理完全缓解(pCR)的获益大于将所有患者都视为pCR或者无病理完全缓解(npCR)。结论:基于MRI影像组学构建的dMMR/MSI-H型局部进展期直肠癌PD-1/PD-L1抑制剂联合全程新辅助放化疗疗效预测模型,有较大潜力为不同基因分型的直肠癌患者制定个体化治疗策略提供量化依据。

AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义

目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-ligand 1,PD-L1)及肿瘤浸润性淋巴细胞(tumor infiltrating lymphocyte,TIL)在三阴性乳腺癌(triple negative breast cancer,TNBC)表达与临床病理特征和预后的关系。方法:根据苏木精-伊红染色(hematoxylineosin, HE)染色切片评判109例TNBC瘤巢内TIL的比例,采用Leica Bond-Max全自动免疫组化仪检测TNBC组织中AR、SKP2、SOX10、PD-L1的表达。分析以上各生物指标与临床病理特征间的关系,并采用kaplan-Meier、Log-rank进行生存分析。结果:95例患者获得随访,中位随访时间为48个月,中位无病生存时间(disease-free survival, DFS)为42个月,中位总生存时间(overall survival, OS)48个月。在TNBC中,AR阳性表达与淋巴结转移阴性(P=0.009)、肿瘤最大径<2 cm(P=0.008)相关,TIL高表达与低级别TNBC相关(P=0.007),SKP2阳性表达与神经/脉管侵犯阳性(P=0.011)、高级别TNBC相关(P=0.002),SOX10阳性表达与淋巴结转移阳性(P=0.022)、高级别TNBC(P=0.005)相关,PD-L1阳性表达与淋巴结转移阳性(P=0.020)、神经/脉管侵犯阳性(P=0.006)、高级别TNBC(P=0.042)相关。生存分析显示,SKP2、SOX10阳性表达与更差的DFS(P=0.007、P<0.001)和OS(P=0.013、P<0.001)相关,TIL高表达与更好的DFS(P=0.016)及OS(P=0.004)相关。在生物表志物的联合表达中,AR+/SKP2-、AR+/SOX10-与更好的DFS(P=0.004、P<0.001)及OS(P=0.007、P=0.001)相关,SOX10+/低TIL、PD-L1+/低TIL与更差的DFS(P<0.001、P=0.008)及OS(P=0.001、P=0.002)相关,AR-/低TIL者具有更差的OS(P=0.014)。SKP2(HR=4.143,95%CI为1.578~10.875)、SOX10(HR=7.578,95%CI为2.067~27.782)的阳性表达是影响TNBC患者DFS的独立预后因子,SKP2(HR=3.758,95%CI为1.400~10.084)、SOX10(HR=5.131,95%CI为1.316~20.000)及TIL(HR=0.375,95%CI为0.154~0.917)的阳性表达是TNBC患者OS的独立预后因子(P均<0.05)。结论:在TNBC中,AR阳性、TIL高表达与具有更好预后的临床病理特征相关,SKP2、SOX10和PD-L1与具侵袭性的临床病理特征相关。SKP2、SOX10及TIL表达与TNBC预后相关,提示这些生物指标可能成为TNBC新的预后因子,同时它们也有可能成为潜在的治疗靶点。

基于King达标理论的心理干预结合亲情干预模式对BPH患者行PKEP术后恢复情况及GQOLI-74、IPSS评分的影响

目的研究基于King达标理论的心理干预结合亲情干预模式对前列腺增生(BPH)患者行经尿道双极等离子前列腺剜除术(PKEP)术后恢复情况及生活质量综合评定问卷(GQOLI-74)、国际前列腺症状评分(IPSS)的影响。方法选择2017年8月~2019年2月浙江省嘉兴市第二医院收治的BPH患者120例作为研究对象,采用随机数字表法将其分为对照组和观察组,每组60例.两组患者均采取PKEP治疗,手术治疗后,对照组患者采取常规护理措施,观察组患者采取基于King达标理论的心理干预结合亲情干预模式,两组患者的护理时间均为4周。比较两组患者的围术期指标、症状改善情况、并发症、生命质量以及依从性之间的差异。结果两组IPSS评分、最大尿流速(Qmax)、残余尿量(RUV)组内治疗前后比较,差异均有统计学意义(均P<0.05),治疗后两组手术时间、术中出血量、切除组织量、IPSS评分、Qmax、RUV之间比较,差异均无统计学意义(P>0.05);治疗后,两组患者的生命质量评分均升高,且观察组患者的生命质量评分均显著高于对照组,差异有统计学意义(P<0.05),两组患者的遵医嘱服药行为以及不良服药行为、日常生活管理行为、烟酒嗜好管理行为、依从性总分均高于治疗前,且观察组各项评分均高于对照组,差异均有统计学意义(P<0.05)。结论通过对BPH患者基于King达标理论的心理干预结合亲情干预模式护理,患者GQOLI-74、IPSS评分显著改善,患者的并发症显著下降,对患者的治疗具有积极的意义。

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic disrupted healthcare in the United States.AIM To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease(IBD)decedents.METHODS We performed a register-based study using data from the National Vital Statistics System,which reports death data from over 99%of the United States population,from January 1,2006 through December 31,2021.IBD-related deaths among adults 25 years and older were stratified by age,sex,race/ethnicity,place of death,and primary cause of death.Predicted and actual age-standardized mortality rates(ASMRs)per 100000 persons were compared.RESULTS 49782 IBD-related deaths occurred during the study period.Non-COVID-19-related deaths increased by 13.14%in 2020 and 18.12%in 2021[2020 ASMR:1.55 actual vs 1.37 predicted,95%confidence interval(CI):1.26-1.49;2021 ASMR:1.63 actual vs 1.38 predicted,95%CI:1.26-1.49].In 2020,non-COVID-19-related mortality increased by 17.65%in ulcerative colitis(UC)patients between the ages of 25 and 65 and 36.36%in non-Hispanic black(NHB)Crohn’s disease(CD)patients.During the pandemic,deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased.CONCLUSION IBD patients suffered excess non-COVID-19-related death during the pandemic.Excess death was associated with younger age among UC patients,and with NHB race among CD patients.Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

TRUE KINGLY HONOUR IN SHAKESPEARE′S HENRY IV PART I

Honour, one of the eternal themes in Shakespeare, is again in the spotlightin Henry IV Part I. In this play, the rivalry between Prince Hal and Hotspuremerges actually out of their cravings for the title of royal honour and valour.Hotspur appears to be formidable, courageous and energetic. He is exactly

Sudden cardiac death in a case of Crohn's disease with COVID-19: A case report

Rationale:The mechanism of sudden cardiac death in COVID-19 can be multifactorial.Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases.Cytokine storm syndrome and idiosyncratic reaction with mesalazine use may lead to sudden cardiac death in COVID-19.Use of immunosuppressants in hospitalized COVID-19 patients should be continued with caution,especially in patients with inflammatory bowel disease.Patient’s concern:A 75-year-old man who was tested positive for SARS-CoV-2 was admitted with a history of shortness of breath for the last two days.He was a known case of Crohn’s disease treated with mesalazine.Diagnosis:COVID-19 pneumonia with underlying Crohn’s disease leading to sudden cardiac death.Intervention:Remdesivir,antibiotics,steroids,low molecular weight heparin,tablet zinc,tab vitamin C,and other supportive treatment were started.Because of increased inflammatory markers,itolizumab was given to the patient on the 2nd day.Outcome:On the 5th day of the intensive care unit,the patient complained of sudden chest pain with respiratory distress leading to bradycardia and asystole and could not be resuscitated.Lessons:Causes for sudden cardiac death in COVID-19 pneumonia patients with Crohn’s disease is multifactorial.Although mesalazine may be a safe and effective drug in the management of inflammatory bowel disease,it can induce sytokine strom syndrome and idiosyncratic reactions that could be one of the reasons of sudden cardic death.Therefore,we should be aware of its serious and potentially life-threatening complications,especially in COVID-19 infected patients.

Jordan＇s King Hussein＇s Peace Initiative and the Treaty with Israel： Overcoming Domestic and Foreign Pressures

The Wadi ＇Araba peace treaty which Jordan＇s King Hussein signed with Israel on October 26, 1994 became a target of criticism ever since it became known to the Jordanian public. Intense pressure was exerted on the Jordanian government to revoke the treaty even before its signature. The opposition to it reached its peak in the following year, when the tension in the holy sites in Jerusalem mounted. Given the persistence of the Arab-Israeli conflict and the fact that the Palestinian issue remained unresolved, it was clear that the King was aware of the potential danger of signing a peace accord with Israel, and that he was prepared to face criticism not only from the Arab states but also from nationalists, Islamists and Leftists all of whom disapproved of his decision. Yet the King remained undeterred and boldly carried on the discussions that culminated in the peace treaty＇s signature. Bearing in mind the fact the Egypt was the first country to sign a peace treaty with Israel it seemed as if there was little risk involved in the normalization process, and that the opposition to the treaty would soon subside. As it turned out, however, the pressure to abrogate it continues to mount.

＂From a Utopia to a Dystopia＂ On Mark Twain＇s Compliance with and Deviation from Heterotopology in A Connecticut Yankee in King Arthur＇s Court

In this paper, the author intends to parallelize Mark Twain＇s A Connecticut Yankee in King Arthur＇s Court with Foucault＇s theorizations about heterotopia, or heterotopology. For Foucault, heterotopia is a paradox because it is paces that are both real and placeless. Twain＇s novel is a time travel story, which juxtaposes the temporalities of the 6th and 19th centuries. In the story, Hank, the hero, is allowed access to Camelot, King Arthur＇s court. Above all, he has introduced to it quite a few elements of modem technology and civilization. So far Twain seems to have complied with Foucault＇s heterotopology. That is, there is a textual heterotopia created in his novel. However, the last principle of Foucault＇s heterotopology states that a heterotopia can be comparable to a utopia because of its contrastive function. A typical time travel story has the same contrastive function as well. That is, in either case there should be a utopia, a dystopia, or a mixture of them. However, Twain＇s novel fails to contrast the 6th century with the 19th century simply because the heterotopia Hank has created leaps from a utopia to a dystopia. It is at this point where Twain has deviated from heterotopology. The shifting nature of this heterotopia not only disables its contrastive mechanism but also jeopardizes its thematic clarity. Most of all, it indicates that Twain has a considerably ambivalent attitude towards the industrial civilization, and that as a consequence, he is indecisive about the direction of this novel.

Re-Formulation of Mean King’s Problem Using Shannon’s Entropy

Mean King’s problem is formulated as a retrodiction problem among noncommutative observables. In this paper, we reformulate Mean King’s problem using Shannon’s entropy as a first step of introducing quantum uncertainty relation with delayed classical information. As a result, we give informational and statistical meanings to the estimation on Mean King problem. As its application, we give an alternative proof of nonexistence of solutions of Mean King’s problem for qubit system without using entanglement.

TCL——King Brand Colour TV Rivals the World's Famous Brands

World famous colour TVs,such asSony,National and Toshiba,usedto monopolize China’s large-screencolour TV market.But recently the KingBrand colour TV made by the TCL ElectronicsGroup has begun to challenge them.In1995,the TCL King Brand colour TV notonly ranked first for its sales volume on theChinese market among the domestically-produced TVs of its kind,but also

An Analysis of Shakespeare's Treatment of Women in King Lear

This paper analyzes Shakespeare’s different treatment of the male and female antagonists Edmond and Goneril in King Lear from their entrance,actions and ending,aiming at exploring his attitude toward women through the comparative studies of these two equally evil characters with different gender.Through the analysis,the author found that Shakespeare’s treatment of women is different from that of men.He is less tolerant and mercy to women than to men,from which a conclusion can be drawn that Shakespeare cannot totally get rid of the traditional conceptions that women is inferior than men even though he is a humanist.

Linkage between PTK Signaling Pathway “Crosstalking” and Caspase-3/CPP32-like Proteases Activation in Signaling Transduction of CD4^+ T Lymphocytes Apoptosis Induced by Superantigen SEB

Exposure of naive murine CD4 + T lymphocytes to superantigen such as staphylococcal enterotoxin B (SEB) induces a strong proliferative response. Prolonged exposure or subsequent restimulation of the responding T cell population with SEB leads to the apoptotic events of activation-induced cell death (AICD). The signaling mechanism responsible for the AICD is a target of intensive investigation. However, the precise downstream signaling pathways of SEB-induced AICD remains unclear. Our results here show that the sequential activation of caspase-1/ICE-like and caspase-3/CPP32-like cysteine proteases probably plays a role in the signaling transduction of SEB-induced AICD, but caspase-3/CPP32-like proteases activation does not depend on caspase-1-like proteases activation. Herbimycin A, a specific inhibitor of protein tyrosine kinases, inhibit caspase-3/CPP32-like cysteine proteases activation. However, it does not prevent DNA fragmentation of CD4 + T cells apoptosis induced by SEB. These results indicate that protein tyrosine kinases pathway is probably involved in the signaling transduction of CD4 + T cells apoptosis induced by SEB and “crosstalks” with the pathway of caspase-3/CPP32-like proteases activation.

Sun Zhigang's Death and Reform of Detention System

The Measures on Aid and Management for Urban Vagrants and Beggars, issued by the State Council in mid-July, took effect on August 1. It marks a further improvement of China’s mechanism to aid urban vagrants and beggars. The new regulation has been enacted to replace the two-decade-old Measures for the Internment and Deportation of Urban Vagrants and Beggars. This policy reform has stemmed from the astounding case of Sun Zhigang, a young man that was brutally beaten to death while in custody at the Guangzhou Detention Center.