白细胞介素17在乙肝肝纤维化中的表达及意义

目的:探讨白细胞介素17(IL-17)与慢性乙型肝炎病毒(HBV)相关件肝病特别足乙肝肝纤维化发生的相关性.方法:酶联免疫吸附试验(ELISA)及逆转录一多聚酶链反应(RT-PCR)法分别测定36例慢乙肝、42例肝硬化(Child-pughA、B、C分别为15、12、15例)、34例原发性肝癌、30例慢性重型乙型肝炎及20例健康对照者血清中的IL-17和外周血单个核细胞(PBMC)中IL-17mRNA水平及肝硬化Child-pugh分级患者血清中的IL-17和肝纤维化指标Ⅳ型胶原(C-Ⅳ),层黏连蛋白(LN),透明质酸(HA)的浓度.结果:与正常对照组相比,血清IL-17和PBMC中IL-17mRNA.水平在4组病人中表达升高(P<0.01);与其他各组相比,IL-17及mRNA水平在肝硬化中升高尤其明显(P<0.01).肝硬化患者血清IL-17及肝纤维化指标水平在Child-pugh C组高于Child-pugh A和Child-pugh B组,Child-pugh B组高于Child-push A组(P<0.01).IL-17水平与Child-push分级评分及C-Ⅳ,LN,HA浓度均呈正相关(r=0.582、0.568、0.682、0.764,P<0.01).结论:IL-17在慢性HBV相关性肝病尤其是乙肝肝硬化中表达明显升高,IL-17可能与慢性HBV相关性肝病尤其是乙肝肝纤维化的发生有明显的相关性.     

儿童慢性乙肝肝组织病理与相关标志物的研究

目的 分析乙肝病毒核内共价闭合环状DNA（HBV cccDNA）、肝纤维化血清标志物、乙肝病毒基因型与肝脏纤维化和炎症活动度的相关性,以了解其在乙肝诊断中的价值,指导治疗和预后.方法 2008年4月至2011年8月于甘肃省人民医院儿科和兰州大学第一医院感染科门诊就诊和住院的乙肝及HBV携带患儿为慢性乙肝组和HBV携带组,选择同期健康查体儿童为对照组.检测慢性乙肝组、HBV携带组和对照组血清HA、LN、PCⅢ和CⅣ.依据病情严重程度,慢性乙肝组进一步分为轻度、中度和重度亚组;慢性乙肝组和HBV携带组检测血清HBV cccDNA和HBV基因型;分析HBV cccDNA、肝纤维化血清标志物、HBV基因型与肝脏纤维化和炎症活动度的相关性.结果 46例患儿进入分析,男34例,女12例,年龄1～16岁,平均年龄（11.8±3.7）岁.HBV携带组20例,慢性乙肝组26例（轻度13例、中度8例、重度5例）,对照组20例.①随乙肝临床分度加重,血清HA、LN、PCⅢ和CⅣ呈升高趋势,以重度乙肝亚组上升最为明显;②随肝组织纤维化程度与炎症活动度的增加,血清HA、LN、PCⅢ和CⅣ呈升高趋势;③血清HBV cccDNA阳性组与阴性组在肝组织炎症活动度〈G2级比例的差异无统计学意义（29/35 vs 9/11,P=0.963）;在肝组织纤维化〈S2期比例的差异无统计学意义（31/35 vs 9/11,P=0.736）;④HBV B基因型患儿肝炎症活动度和纤维化程度显著高于C基因型.结论 血清HBV cccDNA水平与肝纤维化和炎症活动度无相关性;血清HA、LN、PCⅢ和CⅣ,HBV基因型与肝纤维化和炎症活动度有较好的相关性.临床可结合病毒复制水平、丙氨酸氨基转移酶、肝纤维化血清标志物及HBV基因分型综合判断肝损害程度.     

肝硬化患者肝活检组织中IL-8 mRNA表达

目的 探讨肝硬化患者外周血IL-8含量及肝活检组织中IL-8 mRNA的表达.方法 筛选典型HBV感染后肝硬化患者,以ELISA法检测血清IL-8水平;实时PCR检测肝活检组织中IL-8mRNA含量,以lg cDNA/Ig GAPDH(甘油醛-3-磷酸脱氢酶)代表其mRNA水平.结果 肝硬化患者血清IL-8及肝活检组织中其mRNA水平分别为(431.39±97.39)μg/L、1.3647±0.2203,与对照组比较差异有统计学意义(P<0.01);肝活检组织HBV-DNA(+)者血清IL-8及肝活检组织内其mRNA水平分别为(502.43±102.24)μg/L、1.5142±0.2245,与HBV-DNA(-)者相比,差异有统计学意义(P<0.01,P<0.05).丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)升高者血清IL-8及肝活检组织内其mRNA明显升高,与对照组差异有统计学意义(P<0.01).结论 肝硬化患者外周血IL-8及肝活检组织内IL-8 mRNA表达增高,并与肝内HBV复制水平、肝细胞损伤程度密切相关.IL-8参与肝内局部炎性浸润,有可能在介导肝炎后肝硬化进展中起一定作用.     

乙型肝炎肝硬化患者乙型肝炎病毒DNA水平与肝纤维化程度的关系

目的 探讨乙型肝炎肝硬化患者乙型肝炎病毒(HBV)DNA水平与肝纤维化程度的关系及其临床意义.方法 回顾性分析2004年至2006年本科室收治的263例乙型肝炎肝硬化住院患者的临床资料.所有患者均进行肝功能Child-Pugh分级,检测HBV DNA、HBV血清标志物、透明质酸(HA)、人Ⅲ型前胶原(Hpc-Ⅲ)、Ⅳ型胶原(Ⅳ-C)、层粘蛋白(LN);行腹部超声检测脾大小、门静脉内径、脾静脉内径;胃镜检查食管静脉曲张程度,并记录常见并发症.根据HBV DNA水平分为4组:G1组,HBV DNA＜103拷贝/ml;G2组,HBV DNA 103～＜105拷贝/ml;G3组,HBV DNA 105～＜107拷贝/ml;G4组,HBV DNA≥107拷贝/ml.比较各组间Child-Pugh分级、肝纤维化血清指标和门脉高压指标的差异以及各组肝硬化常见并发症的发生情况.结果 263例患者中217例(82.5%)HBV DNA阳性.不同HBV DNA水平患者之间的Child-Pugh评分分级、HA、Hpc-Ⅲ、Ⅳ-C、LN比较,差异无统计学意义(均P＞0.05).4组患者之间脾大小、门静脉内径、脾静脉内径及食管静脉曲张程度比较,差异无统计学意义(均P＞0.05).4组患者并发症如消化道出血、继发感染、腹水、肝性脑病、肝癌等发生率差异也无统计学意义(均P＞0.05).结论 绝大部分乙型肝炎肝硬化患者HBV DNA阳性,但血清HBV DNA水平高低与肝硬化严重程度及并发症的发生率无明显关联.     

血清肝纤维化指标在各型肝病诊断中的应用

探讨联合检测层粘连蛋白（LN）、IV型胶原（C IV）、血清透明质酸（HA）和Ⅲ型前胶原（PCⅢ）在肝纤维化诊断中的应用价值。采用放射免疫分析法检测143例肝病患者的LN、C IV、HA、PCⅢ,同时与41名健康体检者进行比较。结果显示：各组肝病患者血清肝纤维化指标均高于正常对照组（P〈0.01）,且与慢性肝炎病情严重程度密切相关,在慢性肝炎重度组和肝硬化组中表达最高,以HA、PCⅢ升高最为显著。结论：血清LN、C IV、HA、PCⅢ联合检测可明显提高肝纤维化诊断的准确性和可靠性,对诊断肝纤维化有较高的临床价值,但不能用于慢性肝炎重度和肝硬化的鉴别诊断。     

HA、LN及PⅢP检测在CHB患者肝纤维化的早期诊断中的价值分析

目的:探讨透明质酸(Hyaluronic Acid,HA)、人层黏连蛋白(Laminin,LN)及三型前胶原末端肽(Pciiinp,PⅢP)检测对慢性乙型肝炎(Chronic Hepatitis,CHB)患者肝纤维化的早期诊断价值.方法:回顾性分析2019 年 8 月-2021 年 3 月期间收治经穿刺活检证实CHB患者 63 例的临床资料.另选取同期健康体检者 58例为对照组.分析CHB患者的进展阶段;比较各阶段CHB患者和对照组血清HA、LN及PⅢP水平、肝纤维化分期与HA、LN及PⅢP的水平关系、肝功能(Child-Pugh,CHILD)分级与血清HA、LN及PⅢP的水平关系;HA、LN及PⅢP联合检测对CHB患者肝纤维化的诊断价值.结果:以组织穿刺活检为金标准比较,HA、LN 及 PⅢP 联合检测诊断准确率、灵敏度、特异度分别为 83.82%(57/68)、94.82%(55/58)、40.00%(2/5).肝硬化组血清HA、LN及PⅢP水平均显著高于慢性乙型肝炎重度组、中度组、轻度组和对照组(P＜0.05).肝纤维化分期S4 期血清HA、LN及PⅢP水平均显著高于S2-S3、S0-S1 期和对照组(P＜0.05).CHILD分级C级组血清HA、LN及PⅢP水平均显著高于S2-S3、S0-S1 和对照组.结论:血清HA、LN及PⅢP参与CHB患者肝纤维化的发生与发展,能作为早期疾病诊断CHB肝纤维化和评估病情严重程度的重要指标.     

慢性乙肝患者血清CⅣ、PCⅢ、HA和LN测定及其临床意义

目的 :观察慢性乙型肝炎患者血清中Ⅳ型胶原 (CⅣ )、Ⅲ型前胶原 (PCⅢ )、透明质酸 (HA)和层粘蛋白 (LN)的变化及临床意义。方法 :采用放射免疫分析对 172例受检者 (其中乙肝患者 12 9例 ,正常对照者4 3例 )血清中CⅣ、PCⅢ、HA和LN进行检测。结果 :在慢性乙肝患者血清中CⅣ、PCⅢ、HA和LN水平均较正常对照组显著升高 (p <0 0 1)。随着病程的进展 ,CⅣ、PCⅢ、HA和LN四项指标在患者血清中均呈逐渐上升趋势 ,在肝硬化时达到最高。结论 :在慢性乙型肝炎患者中 ,血清CⅣ、PCⅢ、HA和LN等指标 ,可以较好地反映肝纤维化的程度。     

肝豆状核变性患者肝纤维化血清标志物的变化

目的:探讨肝豆状核变性(HLD)患者的肝纤维化血清标志物:透明质酸(HA)、层粘蛋白(LN)和四型胶原(Ⅳ-C)的变化。方法:对186例HLD患者和39例正常对照组用放射免疫分析检测HA、LN和Ⅳ-C水平。结果:HLD组的HA、LN和Ⅳ-C水平分别为(175.12±73.81)μg/L、(128.60±21.36)μg/L和(87.98±32.74)μg/L显著高于正常对照组(P<0.01)。结论:HLD患者肝纤维化血清标志物水平显著升高,其均有不同程度的肝纤维化的存在。     

慢性乙肝患者肝内IL-23/IL-17信号途径与Treg细胞之间的相互作用

目的探讨慢性乙肝患者体内FOXP3蛋白与炎症因子IL-23/IL-17信号途径之间的相互关系。方法采用qPCR、流式细胞术分析了39例慢性乙肝急性发作(ACLF)、56例慢性乙肝(CHB)及32例健康对照(HC)肝组织及外周血中的FOXP3及IL-23/IL-17信号途径相关炎症因子的表达,免疫组化及荧光共聚焦检测FOXP3在肝组织内的表达,定量PCR检测血清HBV DNA水平,酶联免疫吸附试验检测HBsAg浓度,全自动生化仪检测血清谷丙转氨酶(ALT)水平。结果 CHB患者外周血及肝组织内FOXP3 mRNA表达明显升高,肝内的FOXP3表达水平与患者血液中的HBV DNA水平及乙肝表面抗原(HB-sAg)浓度明显呈正相关。与健康对照组相比,慢性乙肝患者肝脏内的IL-23/IL-17信号通路相关的促炎因子也明显升高,且与FOXP3的表达水平升高呈正相关。结论 HBV感染的肝脏内IL-23/IL-17信号通路的活化并没有有效地被宿主的免疫机制如Treg细胞所抑制。因此,IL-23/IL-17信号通路可能是维持HBV病毒持续性感染的一个机制。     

肝纤维化指标的检测及临床意义

目的 研究血清纤维化指标透明质酸（HA）、IV型胶原（Ⅳ-c）、Ⅲ型前胶原肽（PCⅢ）、层粘连蛋白（LN）水平与肝纤维化指标的关系.方法 对确诊的慢性乙型肝炎及肝硬化患者124例和健康人18例,测定血清纤维化指标水平,33例患者进行肝穿行肝组织炎症及肝纤维化分期.血清纤维化指标行统计学分析.结果 血清中HA与CIV水平在慢性肝炎各相平行,而LN与PCⅢ在慢性肝炎病理分期相同时结果一致,在G4期时PCⅢ结果与正常对照相近.四项指标与对照组比较有明显升高.结论 血清纤维化指标与肝纤维化有一定的相关性,这些指标与临床结合对肝纤维化有一定的价值.LN与PCⅢ在慢性肝炎患者分期G_4前与纤维化程度相一致,联合多项指标检测可在一定程度上提高肝纤维化诊断.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.