【作者】 张磊；

【导师】 王丽波；

【作者基本信息】 吉林大学 ， 儿科学， 2024， 硕士

【摘要】 研究背景:轮状病毒感染性腹泻(Rotavirus Diarrhea,RD)是常见的轮状病毒(Rotavirus,RV)感染性消化道疾病,其发病率高和传染性强对患者健康构成了严重威胁。目前,全球范围内,RV是导致5岁以下儿童急性胃肠炎的主要原因之一,尤其在发展中国家,其对儿童健康的影响尤为显著。感染性腹泻不仅会引起肠内症状,也会导致多种肠外表现。目前对于RD相关肠外表现的流行病学研究鲜少,这限制了研究者们对RD的致病机制的深入理解以及肠外表现的防治策略的制定。长春地区具有独特的气候和地理特征,在RD的流行病学分布方面,存在明显的区域性和季节性特点。因此,有必要就长春地区RD的肠道外表现的特征关系进行分析。目的:本研究目的在于描述在吉林大学第一医院就诊的长春部分地区RD的临床特征,比较其与非RD所致感染性腹泻的临床特征差异;进一步分析RD的基因分型,结合肝功能、心肌酶谱特征、心脏超声及心电图表现,揭示不同基因型RD与肠道外器官损伤的关系。方法:本研究收集了2023年1月至2023年12月在吉林大学第一医院因感染性腹泻入院的病历资料及其粪便样本100份,样本保存在-70℃下备用。依据是否属于RD将其分为RD组、非RD组,各50例(发病季节、性别、年龄分布具有相似性),比较两组患者疾病严重程度(Vesikari评分)、肠道外损伤情况,分析长春地区RD与其他病原体感染性腹泻的临床特征差异。后续使用荧光PCR法确定50例RD患儿的G基因、P基因分型情况。并结合患者肝功能、心肌酶谱中肌酸激酶(Creatine kinase,CK)、乳酸脱氢酶(Lactate dehydrogenase,LDH)、肌酸激酶同工酶(Creatine kinase-MB,CK-MB)、α-羟丁酸脱氢酶(α-hydroxybutyric dehydrogenase,α-HBDH)差异、心电图、心脏超声检查情况,采用pearson相关性分析确定各基因分型与心肌酶谱相关生化因子的相关性。结果:(1)临床特征调查结果:RD病例在冬春季节高发,夏秋季节有所下降,且男性患儿的感染率略高于女性(男性26例,女性24例)。长春地区RD的病例中,患儿年龄大部分集中在6个月～12个月,9个月达峰值。RD的腹泻严重程度发现,多数患儿以中度为主,其次为轻度,重度患儿少见。比较不同腹泻严重程度间发生率差异存在统计学意义(χ~2=626.666,P<0.001)。腹泻严重程度以中度为主,重度较少见。RD组心肌损害的发生率显著高于非RD组,P<0.001,此外,不同年度间病毒分型存在显著差异,特别是G2、G4、P4型在各年度变化显著。RD组的QT间期延长发生率也显著高于非RD组(P=0.012);RD组的CK、CK-MB、ALT和AST水平均显著高于非RD组(P值分别为0.004、0.000、0.041和<0.001);肝脏损害和代谢性酸中毒在非RD组中的发生率较高,但仅代谢性酸中毒在统计学上达到显著性差异(P=0.042)。(2)RD的基因分型与心肌损伤关系结果:50例RD患儿中P8分型占比高于其他分型,其次是G9P8分型,而G9、G2相对较少。不同基因分型间的心肌酶谱指标,仅在CK-MB方面存在显著差异,且G2明显高于其他基因分型。观察长春地区RV的基因分型的心电及超声检查结果不难发现,QT间期延长、心电轴右偏、低电压、心包腔微量积液在不同基因分型患儿间比较并未产生明显差异性。仅G2分型与CK-MB间存在显著正相关,P8分型、G9分型、G9P8分型与各心肌酶谱相关指标间无明显相关性。结论:本研究初步揭示了吉林大学第一医院就诊的长春部分地区RD患者的临床特征和基因分型特点,明确了RD的腹泻严重程度及肠外表现特点,并初步发现CK-MB与G2基因分型关系,为RD的预防和治疗提供了科学依据。未来的研究可进一步探索RD基因型与疾病严重程度及治疗预后之间的关系,以期为临床提供更精准的指导。更多还原

【Abstract】 Background:Rotavirus Diarrhea(RD)is a common gastrointestinal disease caused by rotavirus(RV).Due to its high prevalence and contagious nature,RD significantly threatens patient health.Currently,rotavirus is one of the leading causes of acute gastroenteritis in children under five years old worldwide,with a particularly severe impact in developing countries.RD not only leads to intestinal symptoms but also various extra-intestinal manifestations.The scarcity of epidemiological studies on these extra-intestinal manifestations has limited researchers’ ability to fully understand RD’s pathogenic mechanisms and develop effective prevention and treatment strategies.The city of Changchun,located in the subtropics,has distinctive climatic and geographical characteristics.The epidemiological distribution of RD in this region shows clear regional and seasonal variations.Therefore,it is crucial to investigate the relationship between the characteristics of RD’s extra-intestinal manifestations and the specific conditions in Changchun.Objective:The purpose of this study was to describe the clinical characteristics of RD in Changchun in the First Hospital of Jilin University,compare the clinical characteristics of infectious diarrhea caused by non-RD,further analyze the genotyping of RD,and reveal the relationship between liver function,myocardial enzyme profile,cardiac ultrasound and intestinal organ damage.Methods:In this study,100 medical records were collected for infectious diarrhea from January 2023 to December 2023,and the samples were kept at-70℃ for reserve.According to whether RD was divided into RD group and non-RD group,and 50cases(similar season,sex and age distribution),the disease severity(Vesikari score)and intestinal injury in the two groups were compared,and the clinical characteristics of RD and other pathogens infectious diarrhea were analyzed.The G gene and P genotyping of 50 RD children were determined using fluorescent PCR.And creatine kinase(Creatine kinase,CK),lactate dehydrogenase(Lactate dehydrogenase,LDH),creatine kinase isozyme(Creatine kinase-MB,CKMB),α-hydroxybutyrate dehydrogenase(α-hydroxybutyric dehydrogenase,α-HBDH)difference,ECG,cardiac ultrasound examination,The correlation of each genotyping with the myocardial enzyme profile and related biochemical factors was determined using pearson correlation analysis.Results:(1)Survey results of the clinical characteristics: the incidence of RD cases is high during the winter and spring months and decreases in summer and autumn.Additionally,the infection rate of male children is slightly higher than that of female children(26 males and 24 females).The majority of RD cases in Changchun were observed in children aged between six and 12 months,with a peak incidence at nine months.The severity of diarrhoea in RD was predominantly moderate in most children,followed by mild,and severe was rare.A statistically significant difference was observed in the incidence of diarrhoea between the different levels of diarrhoea severity(χ2=626.666,P < 0.001).The severity of diarrhoea was predominantly moderate,with severe cases being less common.The incidence of myocardial damage in the RD group was significantly higher than that in the non-RD group(P<0.001).Furthermore,there was a significant difference in viral typing between different years,with notable changes in the G2,G4 and P4 types from one year to another.Furthermore,the incidence of prolongation of the QT interval in the RD group was significantly higher than that in the non-RD group(P=0.012).Additionally,the levels of CK,CK-MB,ALT and AST were significantly higher in the RD group than in the non-RD group(P values of 0.The incidence of liver damage and metabolic acidosis was higher in the non-RD group,although only metabolic acidosis reached a statistically significant difference(P=0.042).These findings indicate the epidemiological characteristics and potential genetic background of RD in Changchun,offering valuable insights for the prevention and treatment of this condition.(2)The relationship between genotyping and myocardial injury in RD was investigated.The proportion of P8 typing was higher than that of other typing in 50 children with RD,followed by G9P8 typing.The number of cases of G9 and G2 was relatively low.Significant differences in myocardial enzyme profile indexes were observed between different genotypes,with the exception of CK-MB,where G2 exhibited a significantly higher value than other genotypes.A review of the electrocardiographic and ultrasonographic results of RD genotypes in Changchun revealed that prolonged QT interval,rightward deviation of the electrocardiographic axis,low voltage,and micropericardial effusion did not produce significant differences in the comparison between children with different genotypes.A significant positive correlation was observed between G2 and CK-MB,while no significant correlation was evident between P8,G9,and G9P8 and cardiac enzyme profiles.Conclusion:This study preliminarily revealed the clinical characteristics and genotyping characteristics of RD patients in parts of Changchun in the First Hospital of Jilin University,clarified the severity of diarrhea and parenteral manifestations of RD,and preliminarily found the relationship between CK-MB and G2 genotyping,which provided a scientific basis for the prevention and treatment of RD.Future studies could further explore the relationship between RD genotype and disease severity and treatment prognosis,in order to provide more accurate clinical guidance.更多还原