目的 分析胎龄≤32 周早产儿血小板减少症的特点,并探讨其与支气管肺发育不良(broncho-pulmonary dysplal-sia,BPD)的相关性.方法 选取 2018 年 9 月～2022 年 2 月徐州医科大学附属医院新生儿重症监护室收治的胎龄≤32 周的早产儿作为研究对象,回顾性收集并分析研究对象生后 4 周内的临床资料,根据生后 4 周内最低血小板计数(platelet count,PLT)进行分组,采用单因素及二元 Logistic回归分析方法,分析各组间临床资料的差异及血小板减少症与 BPD的关系,并比较 BPD 组早产儿与非BPD组早产儿在不同胎龄时血小板减少症构成比及生后4 周内PLT水平.结果 共纳入197 例早产儿,发生血小板减少症 134 例,发生率为 68.0%,轻度、中度及重度血小板减少症分别占 52.2%(70/134)、36.6%(49/134)、11.2%(15/134),生后第1 周 PLT达最低值(180×109/L).单因素分析结果显示,PLT 水平与出生体重、胎膜早破、孕母子痫、坏死性小肠结肠炎(necro-tizing enterocolitis,NEC)、败血症、BPD、红细胞增多症、红细胞输注量、有创呼吸机使用天数等临床因素相关,不同程度血小板减少症患儿 BPD发生率及严重程度差异有统计学意义(P＜0.05).应用 Logistic 逐步回归方法(前进法)筛选自变量,以是否发生BPD作为因变量,构建 Logistic回归模型,结果显示,中重度血小板减少症是 BPD 发生的危险因素(OR = 2.983,95%CI:1.027～8.662,P =0.044).结论 早产儿血小板减少症发生率高,PLT在生后第 1 周最低,中度、重度血小板减少症可能与 BPD 发生相关,在临床实践中应加以关注.

目的 探讨血清24S羟基胆固醇(24S-HC)及其联合S100-β、NSE在预测早产儿脑损伤及评估近期预后中的临床价值.方法 选取2019年9月至2021年3月收治的存在脑损伤高危因素的74例早产儿为研究对象,酶联免疫吸附法(ELISA)检测两组患儿生后1 d的血清24S-HC、S100-β、NSE水平;振幅整合脑电图(aEEG)监测脑功能,Gesell发育量表评估神经发育情况.根据早产儿脑损伤诊断标准分为脑损伤组(34例)及非脑损伤组(40例).比较24S-HC及其联合S100-β、NSE诊断早产儿脑损伤的敏感度、特异度,绘制ROC曲线;并分析脑损伤组24S-HC、S100-β、NSE水平与aEEG评分、Gesell发育量表发育商(DQ)的相关性.结果 ①脑损伤组早产儿血清24S-HC、S100-β、NSE水平均高于非脑损伤组,差异有统计学意义(P＜0.001).②24S-HC、S100-β、NSE及三者联合诊断早产儿脑损伤的敏感度依次为85.3％、79.4％、88.2％、94.1％,特异度依次为82.5％、82.5％、85.0％、92.5％,AUC 值依次为0.888、0.838、0.907、0.975.③24S-HC、S100-β、NSE水平与矫正胎龄足月时aEEG评分及矫正胎龄3个月Gesell各能区的DQ值均呈负相关(P＜0.01),且24S-HC同近期预后的相关性更强.结论 血清24S-HC在早期预测早产儿脑损伤中有较高的敏感度、特异度,且与近期预后密切相关,有一定临床应用价值;进一步联合S100-β、NSE可明显提高诊断效能.

目的 比较容量保证(VG)与压力控制(PC)两种机械通气模式在呼吸窘迫综合征(RDS)早产儿中的应用效果.方法 前瞻性选择2017年03月至2021年04月NICU收治的胎龄<32周或出生体质量<1500 g,需要有创机械通气的RDS早产儿作为研究对象,按简单随机法分为VG组和PC组.比较两组拔管前的呼吸机参数及动脉血气,有创机械通气时间、总呼吸支持时间及平均住院时间,并发症发生率及病死率.结果 最终RDS早产儿79例完成研究,男46例、女33例,平均胎龄(30.1±1.2)周,平均出生体质量(1239.0±158.0)g,VG组36例、PC组43例.与PC组比较,VG组在拔管前的平均气道压较低,有创机械通气时间、总呼吸支持时间以及平均住院时间均缩短,差异有统计学意义(P<0.05).结论 在RDS早产儿的机械通气治疗中,VG通气可能是一种更加安全有效的通气方式,但仍需要大样本、多中心的临床试验证实.

Objective To investigate the relationship between early postnatal fluid load and severe complications such as bronchopulmonary dysplasia（BPD）, neonatal necrotizing enterocolitis（NEC）, brain injury in premature infants（BIPI）, hemodynamically significant patent ductus arteriosus（hsPDA） in preterm infants with very low and extremely low birth weight.Methods A total of 147 preterm infants with birth weight less than 1 500 g and gestational age less than 32 weeks who were hospitalized in the Neonatal Intensive Care Unit of the Affiliated Hospital of Xuzhou Medical University from August 2018 to August 2021 were selected as research subjects. According to the occurrence of diseases, they were divided into two groups: an experimental group and a control group. A case-control retrospective study was conducted to compare the differences in fluid intake between the experimental groups（including the BPD group, the NEC group, the BIPI group, and the hsPDA group） and the control group on days 1, 2, 3, and 4 after birth and the total fluid intake in the first four days. A receiver operating characteristic（ROC） curve was plotted to predict the optimal daily fluid intake and total fluid intake in the first four days after birth for preterm infants with very low and extremely low birth weight.Results The total fluid intake in the BPD group, NEC group, BIPI group and hsPDA group on days 1, 2, 3 and 4 and the first four days after birth were higher than those in the control group, with statistical differences（P＜0.05）. In the NEC group, the cut-off values of fluid intake on days 1, 2, 3 and 4 and the first four days were 98.9 ml/kg, 123.5 ml/kg, 131.3 ml/kg, 147.8 ml/kg and 492.1 ml/kg. In the BPD group, the cut-off values of fluid intake on day1, 2, 3, 4 and the first 4 days were 95.3 ml/kg, 112.1 ml/kg, 123.4 ml/kg, 141.4 ml/kg and 476.2 ml/kg. In the BIPI group, the cut-off values of fluid intake on days 1, 2, 3 and 4 and the first four days were 88.6 ml/kg, 95.4 ml/kg, 120.0 ml/kg and 128.6 ml/kg and 430.9 ml/kg. The cut-off values of fluid intake in the hsPDA group were 98.7 ml/kg, 102.7 ml/kg, 124.0 ml/kg, 140.8 ml/kg and 496.5 ml/kg on days 1, 2, 3 and 4 and the first four days, respectively. The ROC curve showed that the cut-off value of fluid intake on the second and fourth day in the BPD group was 0.87 and 0.86, respectively, with the best reference significance.Conclusions High fluid load in preterm infants with very low and extremely low birth weight may increase the risk of BPD, NEC, BIPI and hsPDA.

目的 探讨未足月胎膜早破(PPROM)早产儿生后肠道菌群的特征及其与早发败血症(EOS)的关系,为EOS的早期诊断和治疗提供依据.方法 选择2019年3月—2020年9月徐州医科大学附属医院新生儿科收治的38例PPROM早产儿,根据EOS诊断标准将其分为EOS组(20例)及非EOS组(18例),另外选择10例正常早产儿作为对照组.利用高通量测序技术检测并分析各组早产儿生后1d内粪便样本菌群的差异.结果 在多样性分析中,3组粪便菌群的Chao1指数差异无统计学意义,EOS组的Shannon指数显著低于非EOS组及对照组,差异有统计学意义(P<0.05).在门水平上,3组之间厚壁菌门、变形菌门和拟杆菌门的相对丰度差异无统计学意义(P>0.05);EOS组的放线菌门相对丰度低于对照组(P<0.05).在属水平上,EOS组的克雷伯菌属相对丰度高于非EOS组及对照组,EOS组的肠球菌属低于非EOS组及对照组,EOS组的梭菌属、乳杆菌属、双歧杆菌属低于对照组,非EOS组的脲原体属及链球菌属高于对照组,差异均有统计学意义(P<0.05).5例血培养阳性患儿所鉴定出的病原菌均为肠道菌群中相对丰度最高的菌属.结论 PPROM早产儿肠道菌群的多样性降低,克雷伯菌属、葡萄球菌属等条件致病菌的相对丰度升高,有益菌的相对丰度降低可能与EOS的发生有关.

目的 探讨血浆中脂氧素A4(LXA4)和基质金属蛋白酶9(MMP9)的动态变化及对早产儿支气管肺发育不良(BPD)的预测价值.方法 选择2018年1—7月入住徐州医科大学附属医院新生儿科32周以下的早产儿50例,根据BPD的诊断标准为BPD组(20例)和非BPD组(30例),采用酶联免疫吸附法(ELISA)检测病儿第1、7、14天血浆中LXA4、MMP9的表达水平.结果 生后第1天BPD组和非BPD组血浆LXA4表达水平[(330.4±21.6)比(321.1±35.9)pg/mL],差异无统计学意义(P>0.05);BPD组第7天LXA4水平为(281.8±7.0)pg/mL,第14天LXA4水平为(188.4±5.7)pg/mL,随着时间推移逐渐下降,各时间点均低于非BPD组,不同时间点之间两两比较均差异有统计学意义,非BPD组LXA4水平逐渐上升,于第7天达到峰值(348.6±4.4)pg/mL,后又逐渐下降至第14天的(270.3±5.4)pg/mL,不同时间点之间两两比较均差异有统计学意义(P<0.05);第1天BPD组和非BPD组血浆MMP9表达水平(23.9±3.9)ng/mL比(25.3±2.6)ng/mL,差异无统计学意义(P>0.05),BPD组血浆MMP9水平逐渐上升,且生后第7、14天BPD组血浆MMP9水平[(32.6±3.9)ng/mL、(39.0±2.1)ng/mL]均高于非BPD组[(28.8±2.9)ng/mL、(32.2±3.4)ng/mL],不同时间点之间两两比较差异有统计学意义(P<0.05).依据BPD组和非BPD组LXA4浓度绘制ROC曲线下面积为0.670(95％可信区间为0.580～0.759),依据BPD组和非BPD组MMP9浓度绘制ROC曲线下面积为0.749(95％可信区间为0.667～0.830).结论 生后7 d检测血浆LXA4和MMP9的表达水平对早产儿支气管肺发育不良有早期预测价值.

目的 探讨早产儿外周血胱抑素C(cystatin C,Cys C)水平变化及其临床意义.方法 选取2018年1月—2018年6月于徐州医科大学附属医院新生儿科住院治疗的早产儿89例,男47例,女42例,平均胎龄(32.78±2.26)周,平均体重(1.94±0.48)kg,采用颗粒增强透射免疫比浊法检测其生后第3天外周血Cys C水平,采用SPSS 18.0软件进行统计学处理,比较不同胎龄、性别、出生体重、生产方式、Apgar评分及母亲有无合并妊娠期高血压、胎膜早破时Cys C水平差异,分析Cys C和胎龄、出生体重、Apgar评分、肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)、血清总胆红素(total bilirubin,TBIL)水平的相关性.结果 早期早产儿Cys C水平明显高于中、晚期早产儿,差异有统计学意义(P<0.05),中、晚期早产儿比较差异无统计学意义(P>0.05);极低出生体重早产儿CysC水平高于低出生体重及正常出生体重早产儿,差异有统计学意义(P<0.05),而低出生体重早产儿与正常出生体重早产儿比较差异无统计学意义(P>0.05);3、5分钟Apgar评分<8分的早产儿Cys C水平明显高于>8分早产儿,差异有统计学意义(P<0.05);母亲合并胎膜早破的早产儿Cys C水平高于无胎膜早破早产儿,差异有统计学意义(P<0.05);不同性别、生产方式、TBIL水平及母亲有无合并妊娠期高血压早产儿Cys C差异无统计学意义(P>0.05).相关分析显示:Cys C水平与Cr、BUN呈明显正相关(P<0.05),与胎龄、出生体重、Apgar评分呈负相关(P<0.05),但相关关系不密切(r<0.5),与TBIL水平无相关性(P>0.05).结论胎龄、出生体重、5分钟Apgar评分、母亲合并胎膜早破均为早产儿Cys C水平的影响因素,胎龄越小、出生体重及5分钟Apgar评分越低早产儿Cys C水平越高,且呈负相关,此类早产儿应高度警惕肾脏损害存在,而性别、生产方式、TBIL水平及母亲合并妊娠高血压对Cys C水平无明显影响.

目的:探讨巨细胞病毒性肝损伤患儿外周血CD4+CD25+调节性T细胞(CD4+CD25+regulatory T cells,Treg)、辅助性T细胞17(Th17)、IL-17及IL-35水平及其临床意义.方法:选取20例巨细胞病毒感染肝损伤患儿为肝损伤组,18例巨细胞病毒感染无肝损伤患儿为非肝损组,同期20例体检健康婴儿为对照组;采用荧光免疫PCR(FQ-PCR)法检测尿HCMV-DNA载量,流式细胞术检测外周血Th17、Treg细胞比例,ELISA法检测血浆IL-17、IL-35浓度,同时测定血清丙氨酸转移酶(ALT)含量,分析细胞比例与细胞因子之间的关联.结果:① 与对照组比较,肝损伤组婴儿外周血Th17细胞比例、IL-17浓度明显升高,且两者呈显著正相关(P均<0.05);② 肝损伤组Treg比例及IL-35浓度显著低于非肝损组和正常对照组,且Treg与IL-35间呈显著正相关(P<0.05);肝损伤组Th17/Treg比值明显高于非肝损组和对照组(P均<0.05).③肝损伤组外周血ALT显著高于非肝损组和对照组(P均<0.05),非肝损组和对照组间ALT无明显差异(P>0.05).结论:IL-17、IL-35与巨细胞病毒感染引起的肝损伤密切相关,Th17/Treg的平衡在维持巨细胞病毒感染患儿机体免疫内环境稳定中起着重要作用.

目的 探究分析巨细胞病毒(CMV)感染患儿发生肝功能损伤的临床特点和危险因素.方法 回顾性分析2015年1月-2017年12月在该院初次确诊为巨细胞病毒感染婴儿的临床资料,分析其临床特点和危险因素.结果 肝功能损伤组患儿与非肝功能损伤组患儿比较,外周血中性粒细胞/淋巴细胞比率(NLR)及CD16+ CD56+ NK细胞比例差异有统计学意义(P＜0.05),而白细胞总数、淋巴细胞计数、中性粒细胞计数、患儿年龄、性别、CMV病毒载量以及炎症指标[C-反应蛋白(CRP)、α-酸性糖蛋白]差异无统计学意义(P＞0.05).结论 NLR及NK细胞比例降低与CMV感染患儿发生肝功能损伤密切相关,同时NLR较传统炎症指标对CMV感染患儿肝功能损伤具有更好的诊断和预测价值.

目的 探讨白细胞介素-33(IL-33)、可溶性致癌抑制因子2(sST2)在婴儿巨细胞病毒(HCMV)肝炎中的表达及意义.方法 选取HCMV感染婴儿40例,其中肝炎组20例,其他疾病组20例;另选择同期健康婴儿20例作为对照组.采用ELISA法检测三组婴儿血浆IL-33、sST2、IFN-γ、IL-4浓度,采用流式细胞术检测外周血Th1、Th2细胞比例.结果 HCMV阳性肝炎组和HCMV阳性其他疾病组患儿的血浆IL-33、sST2、IFN-γ、IL-4浓度及Th1、Th2细胞比例均高于对照组,肝炎组高于其他疾病组.肝炎组和其他疾病组患儿IFN-γ/IL-4及Th1/Th2均低于对照组,肝炎组低于其他疾病组,差异均有统计学意义(P<0.05).HCMV肝炎组血浆IL-33浓度与sST2、IL-4浓度及Th2细胞比例呈显著正相关(P<0.05),与IFN-γ/IL-4、Th1/Th2呈显著负相关(P<0.05).结论 HCMV肝炎婴儿存在Th1/Th2失衡,IL-33可能参与HCMV感染所致Th2优势应答和Th1/Th2失衡.

目的 探讨妊娠期宫内感染对胎龄＜37周早产儿免疫指标的影响及相关机制,为临床诊治提供参考依据.方法 收集2016年10月-2018年4月在徐州医科大学附属医院娩出的早产儿189例为研究对象,其中宫内感染组86例,未感染组103例.比较出生后24 h、7d的外周血T淋巴细胞亚群(CD3+、CD4+、CD8+)、免疫球蛋白(IgG、IgM、IgA)、白细胞介素(IL-6、IL-8、IL-1β)及肿瘤坏死因子(TNF-α)水平.收集脐带血,分离脐带血单个核细胞(UBMC),RT-PCR检测细胞中Tlr2、Tlr4、Socsl、Socs3 mRNA表达水平;使用细菌脂多糖LPS刺激未感染组UBMC,检测不同刺激时间(lh、3h、6h、12 h)的Tlr2、Tlr4、Socs1、Socs3 mRNA表达水平.结果 出生后24h、7d感染组早产儿血清CD3+、CD4+、CD8+水平明显高于未感染组,IgG、IgM、IgG水平明显低于未感染组,IL-6、IL-8、IL-1β、TNF-α水平明显高于未感染组(均P＜0.05).感染组早产儿UBMC中Tlr2、Tlr4、Socs1、Socs3 mRNA表达水平明显高于未感染组(均P＜0.05).LPS刺激各时间点Tlr2、Tlr4、Socs1、Socs3 mRNA表达水平均明显高于空白对照组(均P＜0.05);其中Tlr2 mRNA表达在LPS刺激3h时达到峰值,Tlr4 mR-NA表达在LPS刺激1h时达到峰值,Socs1和Socs3 mRNA表达在LPS刺激3h时达到峰值.结论 宫内感染可引发早产儿体内免疫指标异常改变,其机制可能通过Toll样受体和Socs信号通路调节体内免疫反应.

OBJECTIVE To investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-β1 (TGF-β1), in infants with human cytomegalovirus (HCMV) infection. METHODS Twenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-β1 in plasma were measured using ELISA. RESULTS Compared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-β1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-β1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-β1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-β1 level (P>0.05). CONCLUSIONS There is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.

Objective To investigate the effects of sodium aescinate(SA) on the expressions of absent in melanoma 2(AIM2),Caspase-1 and matrix metallopeptidase 9(MMP-9) in the brain tissues of the mice with cytomegalovirus infection.Methods Fifty-four newborn Balb/c mice were intraperitoneally injected murine cytomegalovirus(MCMV) suspension(TCID50 104.44U/ml,20μl) to establish the mouse models of disseminated MCMV infection,which were randomly and equally divided into three groups of A(model control),B(intraperitoneally injected SA 5mg·kg-1·d-1) and D(intraperitoneally injected ganciclovir 60mg·kg-1·d-1).Another 18 mice were selected as the blank controls(group C).Groups of A and C were intraperitoneally injected an equal volume of normal saline.On the 7th,14th and 21st day after administration,the MCMV-DNA expression in brain tissues was determined by PCR and the protein expressions of AIM2,Caspase-1 and MMP-9 in brain tissues were detected by Western blot.Results The MCMV-DNA expression in brain tissues was seen in groups of A, B and D.At each time point, the MCMV-DNA expression in group B was higher than that in group D(P<0.05), but lower than that in group A(P<0.05).The protein expressions of AIM2,Caspase-1 and MMP-9 in brain tissues were higher in groups of A,B and D than those in group C(P<0.05).At each time point,the protein expressions of AIM2,Caspase-1 and MMP-9 in group D were higher than those in group B,but lower than those in group A(P<0.05).The expressions of AIM2,Caspase-1 and MMP-9 in groups of B and D were lower on the 21st day than those on the 7th day,while group A showed an opposite trend in the expressions of above proteins(P<0.05).Conclusion AIM2,Caspase-1 and MMP-9 are involved in the inflammatory process of MCMV-related brain damage.SA can reduce MCMV-related brain damage by inhibiting neuronal pyroptosis.