目的 观察低出生体重早产儿应用抗生素后肠道菌群的动态变化。方法 选取2018年6月—2019年7月在广州市第一人民医院住院的10名低出生体重早产儿,在出生时、出生后1~2周、出生后2~3周、出生后3~4周、出生后4~5周、出生后5~6周时分别收集粪便样本,通过16s高通量测序检测患儿粪便菌群变化并统计分析。结果 应用抗生素后的低出生体重早产儿肠道菌群α多样性(Shannon指数、Simpson指数、ACE指数和PD_whole_tree指数)下降(P均<0.05),肠道菌群结构在门、科、属水平均发生改变,其中Alistipes、Bacteroides、Lactobacillus、unidentified_Lachnospiraceae、unidentified_Ruminococcaceae、Alloprevotella、unidentified_Cyanobacteria、Bacillus、Stenotrophomonas和Acinetobacter菌属相对丰度减少(P均<0.05)。结论 低出生体重早产儿应用抗生素后肠道菌群多样性下降,肠道菌群结构发生改变,并在抗生素停用后仍持续,针对性补充益生菌或益生元可能有助于肠道菌群恢复稳态。

Objective To observe the dynamic changes of gut microbiota in premature infants with low birth weight after antibiotics therapy. Methods 10 low birth weight premature infants hospitalized in Guangzhou First People's Hospital from June 2018 to July 2019 were included. Fecal samples were collected at birth, 1~2 weeks after birth, 2~3 weeks after birth, 3~4 weeks after birth, 4~5 weeks after birth and 5~6 weeks after birth, respectively. The changes of fecal microbiota were detected and analyzed by 16s high-throughput sequencing. Results The α-diversity of gut microbiota (Shannon index, Simpson index, ACE index and PD_whole_tree index) in low birth weight preterm infants treated with antibiotics decreased (P<0.05). The structure of gut microbiota changed at phylum, family and genus levels, among which Alistipes, Bacteroides, Lactobacillus, unidentified_Lachnospiraceae, unidentified_Ruminococcaceae, Alloprevotella, unidentified_Cyanobacteria, Bacillus, Stenotrophomonas and Acinetobacter decreased (P<0.05). Conclusion The diversity of gut microbiota in low birth weight preterm infants decreased and the structure of gut microbiota changed after antibiotic therapy. Targeted supplementation of probiotics or prebiotics may contribute to the recovery of gut microbial homeostasis.

目的 探讨先天性肥厚性幽门狭窄(congenital hypertrophic pyloric stenosis,IHPS)中神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)的表达情况,以进一步研究IHPS的发病机制。方法 选取4只Beagle孕犬按3:1分为模型组和对照组,自孕期第1天至分娩前1天,模型组孕犬每天腹腔注射一次L-NAME 6 mg/(kg.d),对照组给予同样方式注射等量的生理盐水。所有新生犬均在生后第31天、38天、45天及52天分别称重,生后52天,选取模型组中体质量增长缓慢的新生犬和对照组新生犬各5只作为实验对象,取幽门组织HE染色后显微镜下测量幽门环肌厚度,免疫组化后运用图像分析技术测定nNOS表达量。结果 与对照组新生犬比较,模型组中新生犬体质量增长慢,幽门环肌增厚,nNOS表达量减少,两组间有差异(P<0.01,P<0.01,P<0.05)。结论 幽门区nNOS表达减少与CHPS相关。

Objective To further study the pathogenesis of infantile hypertrophic pyloric stenosis(IHPS) by analyzing the expression of neuronal nitric oxide synthase(nNOS) in pylorus of CHPS. Methods According to 3:1,four Beagle pregnant dogs were selected and divided into model group and control group,from the first day of pregnancy to the first day before delivery, L-NAME was intraperitoneally injected into pregnant dogs in the model group, dose for 6mg/(kg.d),while normal saline was intraperitoneally injected into pregnant dogs in the control group.The two groups newborn dogs were weighed at 31, 38, 45 and 52 days after birth,At 52 days after birth, 5 newborn dogs were selected respectively between model group and control group as experimental subjects, obtained pyloric tissue for HE staining and measured the muscular thickness of pyloric,The expression of nNOS was determined by image analysis after immunohistochemistry. Results Compared with newborn dogs in the control group, newborn dogs in the model group had slow weight growth, increased pyloric annulus muscle thickness, and decreased expression of nNOS(P<0.01,P<0.01,P<0.05). Conclusion The decreased expression of nNOS in the pyloric region associated with IHPS.

目的 分析神经营养类药物单唾液酸四己糖神经节苷脂(monosialotetrahexosylganglioside,GM1)与胞磷胆碱(citicoline)联合使用在新生儿缺血缺氧性脑病(neonatal hypoxic-ischemic encephalopathy,NHIE)的临床疗效并探讨其可能的作用机制。方法 收集2014年1月—2017年6月在广州市第一人民医院新生儿病房住院的54例新生儿缺血缺氧性脑病患儿的临床资料,将收集到的患儿随机分为2组,对照组27例,治疗组27例。治疗组与对照组的治疗的不同在于前者予以单唾液酸四己糖神经节苷脂GM1联合胞磷胆碱治疗,而对照组仅用单唾液酸四己糖神经节苷脂GM1,无用胞磷胆碱。治疗三个疗程后,比较2组用药前后的临床表现、神经功能评分及MRI变化情况。结果 治疗组中临床总有效24例(88.9%);对照组中总有效17例(63.0%)(P<0.05);经过三个疗程后2组的神经功能评分均有上升,且治疗组的效果更明显(P<0.05);MRI检查示2组较用药前病灶范围减少,水肿减轻,治疗组改善更明显(P<0.05)。即经过三个疗程治疗后,两组患儿病情均有好转,且治疗组疗效更明显。结论 神经营养类药物GM1联合胞磷胆碱通过修复、重构神经元、改善其代谢等促进受损的神经功能的恢复,在新生儿缺血缺氧性脑病的应用中具有良好的疗效。

Objective To analysis the clinical therapeutic effect of monosialotetrahexosylganglioside and citicolineon neonatal hypoxic-ischemic encephalopathy, and explore its possible mechanism.Methods A total of 54 newborn with hypoxicischemic encephalopathy were enrolled from January 2015 to June 2017 in Guangzhou First People's Hospital, and they were divided into control group and treatment group according to the treatment methods, with 27 cases in the control group and 27 cases in the treatment group. Both groups were treated with conventional treatment, the control group added gangliosides, and the treatment group used ganglioside and citicoline. The clinical effects, neurological score and MRI were observed in the two groups.Results The total effective rate was 88.9% in the treatment group,which was higher than 73.0% in the control group (P<0.05). There was no significant difference on neurological score between the two groups before treatment (P>0.05). After treatment, the neurological scores of the two groups were significantly improved, and the score of the treatment group was higher than that of the control group (P<0.05). MRI examinations found that the lesions were significantly improved in the two groups after treatments, and the effect of the treatment group was higher than that of the control group (P<0.05).Conclusion Monosialotetrahexosylganglioside combined with citicolineinthe in treatment of newborn with hypoxicischemic encephalopathy has good effects through repairing and rebuilding the neurons, improving the metabolism to promote the recovery of neurological functions.

目的 探讨分析氨茶碱治疗早产儿呼吸暂停的临床疗效及其在治疗过程中所出现的不良事件。方法 选取2014年9—2016年3月广州市第一人民医院新生儿科接受住院治疗的胎龄＜34周,生后2 h内入住新生儿科的早产儿42例。随机分为对照组和氨茶碱组,对照组(20例)给予保暖、吸氧、补充能量、保持呼吸道通畅、物理刺激等对症治疗,不使用氨茶碱及其它改善呼吸的药物;氨茶碱组(22例)患儿除给予对照组治疗措施外,同时给予氨茶碱静脉滴注,首剂负荷量5 mg/kg,在20min内完成,12 h后以2～2.5 mg/kg维持量,每隔12 h一次。观察两组的疗效与不良影响。结果 ①两组患儿性别、出生胎龄、出生体重、产前孕母糖皮质激素的应用、受孕方式、分娩方式、多胎妊娠、5min Apgar评分、机械通气及CPAP辅助通气例数、低-中流量吸氧(箱内或头罩给氧)例数等方面差异均无统计学意义(P均＞0.05)。②与对照组相比,氨茶碱组早产儿呼吸暂停(AOP)发生的次数较少,AOP消失所需时间较短,差异均有统计学意义(P＜0.05)。③不良影响方面,氨茶碱组脑白质发育不良发生率(63.6%,14/22例)显著高于对照组(25%,5/20例),差异有统计学意义(P＜0.05);两组患儿在听力检查异常、喂养不耐受、血糖紊乱、血脂代谢紊乱、血红蛋白下降、电解质紊乱、出院时体重及住院时间等方面均无统计学意义(P均＞0.05)。④氨茶碱组视网膜发育不完全的发生率(40.9%,9/22例)明显高于对照组(15.0%,3/20例),但差异无统计学意义(P＞0.05)。结论 小剂量氨茶碱在防治AOP方面的作用是值得肯定的,但它有可能增加早产儿脑白质发育不良的风险与视网膜发育不完全的风险。

Objective To investigate the clinical efficacy and adverse effects of aminophylline in prevention of apnea of prematurity. Methods Forty-two infants with gestational age ＜34 weeks admitted to department of pediatrics, Guangzhou first people's hospital between Sep. 2014 and Mar. 2016 were randomly divided into 2 groups: control group and aminophylline group. Control group(n=20): 20 infants received warming, oxygen inhalation, supplement energy, maintain airway patency, physical stimulation, such as symptomatic treatment, without aminophylline or any other drugs for improving breathing. Aminophylline group(n=22): In addition to the control group treatment measures, 22 infants received a loading dose of 5 mg/kg of aminophylline and then maintained by a dose of 2mg/kg with intravenous drip q 12 h. Then we compared the efficacy and adverse effects of the two groups. Results ①There was no significant difference in gender, gestational age, birth weight, maternal antenatal glucocorticoid application, pregnancy(including multiple pregnancy) and delivery,5 min Apgar score, oxygen therapy, the application of mechanical ventilation, nasal continuous positive airway pressure, and the low-medium flow oxygen inhalation between the 2 groups(all P＞0.05). ② Compared with the control group, the incidence of apnea in aminophylline group were significant lower, and the time needed for apnea to disappear were significant shorter(all P＞0.05). ③ The incidence of cerebral white matter development dysplasia of aminophylline group(63.6%,14/22 cases) were significant higher than the control group(25%,5/20 cases, P＜0.05). There was no statistically significant difference in hearing loss, feeding intolerance, blood glucose disturbance, blood lipid metabolism disorder, hemoglobin decrease, electrolyte disorder, body weight at discharge, the duration and cost of hospitalization between the 2 groups(all P＞0.05). ④ The incidence of retinal incompleted development of aminophylline group(40.9%, 9/22 cases) were higher than control group(15.0%, 3/20 cases), but there was no statistical significance between the 2 groups(P＞0.05). Conclusion Effects of aminophylline in treating apnea of prematurity is positive, but it is likely to increase the risk of premature brain white matter development dysplasia and the risk of retinal incompleted development.

目的 了解CHPS患儿经胃镜下幽门肌切开术治疗后幽门部黏膜近期各种并发症的发生情况及对预后的影响。方法 选取2006—2012年我院新生儿科确诊的34例CHPS患儿。以超细胃镜进入十二指肠乳头处,使用电切刀按上行性方向,沿幽门管纵轴切割肥厚狭窄的幽门管黏膜及环形肌以解除幽门部梗阻。术后第1、3、6月复查胃镜。结果 34例CHPS患儿共行胃镜下幽门肌切开术48次,均未发生胃及幽门穿孔、撕裂等严重并发症。24例患儿术后通过胃镜进行了复查,胃镜见幽门部及黏膜改变主要有黏膜充血肿胀、切口未完全愈合、切口疤痕形成、幽门部息肉形成等。结论 经胃镜下幽门肌切开术是一种安全性较高的治疗CHPS的新技术。术后黏膜充血肿胀、切口未完全愈合等幽门部黏膜改变的发生率随时间下降。切口疤痕形成并未影响幽门功能。

目的 探讨新生儿早发型B族链球菌(GBS)败血症的临床特点,提高对本病的认识。方法 选取我院2010—2012年我院新生儿重症监护病房(NICU)收治的新生儿资料,回顾性分析GBS的临床表现、实验室检查、治疗和转归。结果 早发型GBS败血症8例,占住院患儿的6.28‰,均为足月儿,生后24小时内发病,以气促、发绀等呼吸系统症状为主,其中4例出现感染性休克表现;实验室检查提示血常规WBC:2.07~14.1×10⁹/L,＜5×10⁹/L 5例,中性粒细胞绝对值0.54~8.32×10⁹/L。胸部X线提示:肺部纹理粗乱,渗出增多。1例需机械通气辅助呼吸。青霉素联合头孢三代或万古霉素治疗有效,重症感染者需加强支持治疗。结论 应重视新生儿早发型无乳链球菌败血症早期呼吸系统症状,尽早诊断和治疗,降低病死率。

Objective To investigate the clinical features of early-on set neonatal Group B Streptococcal (GBS)septicemia in order to guide the clinical diagnosis and treatment. Methods Retrospectively analysing the clinical presentation, laboratory examination, treatment and prognosis of the 8 cases of all newborns from 2010 to 2012 in our hospital. Results The incidence of neonatal early-on set Group B Streptococcal septicemia was 6.28‰.8 cases were full-term infants in this study.Respiratory symptoms such as anhelation and cyanosis were first signs of early-on set Group B streptococcal septicemia within 24 hours after birth; 4 cases of septic shock. Results of laboratory tests included WBC:2.07~14.1×10⁹/L, in which 5 cases were ＜5×10⁹/L, N 0.54~8.32×10⁹/L. Chest X-ray: lung texture showed coarse and disorderly, leakage was increased. One case needed respiratory support with mechanical ventilation. Intravenous treatment of neonatal GBS with penicillin combined with Vancomycin was effective. Patients of serve infections should be provided supportive care. Conclusion Patients of serve early symptom of respiratory system should be paid attention. Early diagnosis and treatment should be as soon as possible to reduce fatalities.

      目的   探讨神经元型一氧化氮合酶（nNOS）在抑制剂N-硝基-左旋精氨酸甲酯（L-NAME）抑制作用下与新生鼠胃肠道疾病的相关性研究，以进一步研究婴儿肥厚性幽门狭窄（IHPS）等疾病的致病机制。方法   对40只成熟雌性wistar大鼠随机均分4组，怀孕后予怀孕母鼠灌胃，对照组给予生理盐水，低剂量组、中剂量组、高剂量组分别给予L-NAME 60、300、600 mg/（kg·d）L-NAME。新生鼠皮下注射方式，予对照组皮下注射生理盐水，在低剂量组、中剂量组、高剂量组皮下注射L-NAME 25、125、250 mg/（kg·d）L-NAME。统计分析新生鼠幽门中的nNOS表达量、体质量增长情况、胃潴留情况、幽门肌层厚度。结果 （1）低剂量组、中剂量组、高剂量组新生鼠幽门肌层厚度在出生后第1、7、14日龄高于对照组，但组间比较差异无统计学意义（P＞0.05）。（2）与对照组相比，低剂量组、中剂量组、高剂量组的新生鼠出生后第1周体质量增加量更少，胃潴留更明显（P＞0.05）；在出生后的第2周各组体质量增加量差异无统计学意义（P＞0.05）。（3）新生鼠出生后第14天，中剂量组的胃体积大于低剂量组，但低剂量组和对照组之间、中剂量组和高剂量组之间比较差异无统计学意义（P＞0.05）。（4）新生鼠生后第1天，幽门中nNOS的表达被L-NAME以剂量依赖的方式被抑制，随着新生鼠日龄的增长，这种效应逐渐消失。（5）在不同剂量L-NAME的作用下，新生鼠幽门中nNOS表达量、趋势在不同时间点不同。结论 （1）nNOS可以导致新生鼠胃潴留、幽门梗阻，与IHPS相关症状之间存在相关性，但可能不是IHPS病因的唯一分子机制。（2）在新生鼠胃、幽门组织中，nNOS的表达量可以通过负反馈调节机制调节。（3）nNOS表达量上调可能有助于幽门舒张，但可能无法完全逆转IHPS中幽门的进一步肥厚和阻塞。

    Objective  To explore the effect of nNOS on the early postnatal pylorus of neonatal rats under the inhibition of the inhibitor N-nitro-L-arginine methyl ester hydrochloride（L-NAME），in order to further investigate the pathogenic mechanism of infantile hypertrophic pyloric stenosis（IHPS）．Methods  Pregnant female mice were grouped randomly and administered by gavage，with the control group receiving physiological saline，the low-dose，medium-dose and high-dose groups  receiving different doses of L-NAME．For the neonatal rats，the control group was subcutaneously injected with physiological saline，while the low-dose group，medium-dose group，and high-dose group were subcutaneously injected with different doses of L-NAME．The expression of nNOS in the pylorus，weight gain，gastric retention，and pyloric muscle thickness of newborn  rats were statistically analyzed．Results   (1) The thickness of the pyloric muscle layer in the low-dose group，medium-dose group，and high-dose group of newborn rats was higher than that in the control group on the 1st，7th，and 14th day after birth，but there was no significant difference．（2）Compared with the control group，the neonatal rats in the low-dose group，the middle-dose group and the high-dose group gained less weight in the first week after birth，and the gastric retention was more significant．There was no significant difference in weight gain among the groups in the second week after birth．（3）On the 14th day after birth，the gastric volume of the medium-dose group was larger than that of the low-dose group，but there was no statistical difference between the low-dose group and the control group，or between the medium-dose group and the high-dose group．（4）On the first day after birth，the expression of nNOS in the pylorus of neonatal rats was significantly inhibited by L-NAME with dose-dependence，and this effect gradually disappeared with increasing age of neonatal rats．(5) Under the action of different doses of L-NAME，the expression level and trend of nNOS in the pylorus of neonatal mice vary at different time points．Conclusions   (1) nNOS can cause gastric  retention and pyloric obstruction in newborn rats，which is related to IHPS related symptoms，but may not be the only molecular mechanism of IHPS etiology．(2) The expression level of nNOS in the pyloric tissue of newborn mice can be regulated through a negative feedback regulatory mechanism．(3) Upregulation of nNOS expression may contribute to pyloric dilation，but may not completely  reverse thickening and obstruction of the pylorus in IHPS．