雾化吸入NO供体对新生猪急性呼吸窘迫综合征炎症反应的干预作用

目的 探讨雾化吸入NO供体对急性呼吸窘迫综合征炎症反应的干预作用机制.方法 健康出生后3～5 d的新生绪45只随机分成5组,A组为对照组:气管插管,接呼吸机;B组为NS组:模型建立后,经呼吸机管道雾化吸入生理盐水30min;C组为模型建立后,经呼吸机管道雾化吸入Neb-SNP(1 mg/ml,0.9%NaCl配制)30 min;D组为模型建立后,经呼吸机管道雾化吸入Neb-SNP(5 mg/ml)30min;E组为模型建立后,,经呼吸机管道雾化吸入Neb-SNP(10mg/ml)30min.各组分30、60、120 min3个时间点各3只测定肺组织核因子(NF)-κB的表达及血清细胞因子TNF-α、IL-12、IL-10的浓度.结果 治疗组肺组织NF-κB表达显著降低(P＜0.05),血清TNF-α、IL-12浓度显著降低(P＜0.05),IL-10浓度明显增高(P＜0.05);Neb-SNP雾化浓度增加,NF-κB表达下降,炎症因子TNF-α、IL-12浓度下降,IL-10浓度升高[C组与D组差异有显著性(P＜0.05),D组与E组差异无显著性(P＞0.05)].结论 Neb-SNP通过下调NF-κB的活性,抑制炎症因子的表达从而减轻急性呼吸窘迫综合征的肺损伤.

Abstract：

Objective To investigate modulatory effects of Neb-SNP on inflammatory response and to explore the protection mechanisms of Neb-SNP in newborn piglets with ARDS. Methods Forty-five neonatal swines were randomly divided into five groups:group A (controlled group ,n = 9), group B (physiological saline group,n =9),group C (Neb-SNP 1 mg/ml,0. 9% NaCl, n = 9), group D (Neb-SNP 5 mg/ml,0. 9% NaCl, n = 9) and group E (Neb-SNP 10 mg/ml,0. 9% NaCl, n = 9). The pathological changes and activity of NF-κB in the lung tissue ,TNF-α ,IL-10 and IL-12 concentrations in serum at 30 minutes,60 minutes and 120 minutes after aerosol inhalation were observed. Results Activity of NF-κB and serum concentrations of TNF-α and IL-12 in the Neb-SNP treated group were lower than group B(P ＜0. 05) ,and serum IL-l0 concentration was obviously higher in the Neb-SNP group(P ＜0. 05). With an increase of Neb-SNP concentration,activity of NF-κB and serum concentrations of TNF-α and IL-12 were obviously increased, while serum concentrations of IL-10 was increased in group D and group E than that of group C (P ＜ 0. 05).Conclusion Inhalation of Neb-SNP reduced lung injury induced ARDS through lowering NF-κB activity and inhibiting expression of harmful inflammatory cytokines.     

硝普钠对乳猪体外循环中肺损伤的保护作用

目的 探讨硝普钠预处理对乳猪体外循环(CPB)中的肺保护作用.方法 20只幼猪,数字随机分为实验组(A组)及对照组(B组).A组CPB前30min股静脉滴入硝普钠(20μg·kg-1·min-1)至实验结束,B组滴入生理盐水.CPB前(T1)、主动脉开放(T2)、CPB后5 min(T3)、20 min(T4)、40 min(T5)、60 min(T6)时点测定气道峰压(Ppk).T1、T3、T6时点行动脉血气分析、血浆TNF-a、IL-6、IL-8、IL-10检测及肺动脉、左心房血中性粒细胞检测.实验结束后,切取3块肺组织行肺湿干比(W/D)测定、光镜及电镜组织形态学观察.结果 中性粒细胞滞留率T6[A组(0.48±0.21),B组(0.77±0.29)]、血清炎症因子水平:TNF-α浓度T3[A组(45.20±14.00)pg/ml,B组(71.19±11.65)pg/ml]、IL-6浓度T3[A组(33.38±9.72)pg/ml,B组(46.09±12.12)pg/ml]、IL-8浓度T3及T6[A组(27.84±11.96)pg/ml、(24.94±1 4.24)pg/ml,B组(56.73±14.78)pg/ml、(40.99±7.94)pg/ml]和IL-10浓度T3[A组(37.88±7.79)pg/ml,B组(27.62±11.53)pg/ml]、氧合指数(OI)T3[A组(463.05±40.50)%,B组(382.62±80.01)%]及动脉-肺泡氧分压比率(Pao2/PAo2)T3及T6[A组(0.75±0.10)、(0.76±0.07),B组(0.56±0.12)、(0.60±0.07)]、气道峰压(Ppk)T3[A组(16.57±1.51)mmHg,B组(23.00±2.00mmHg]以及肺湿干比(W/D)[A组(0.21±0.03),B组(0.27±0.04)].A组与B组相比,差异均有统计学意义.光镜、电镜检查显示A组肺损伤明显减轻.结论 CPB期间,硝普钠预处理能抑制炎症因子上调,减轻急性炎症反应,改善肺功能.

Abstract：

Objective To investigate the protective effects of sodium nitroprusside on lung injury induced by cardiopulmonary bypass (CPB). Methods Twenty piglets were randomly divided into group A (n = 10) and group B (n = 10). The piglets of the group A were administered with sodium nithe end of the experiment. The piglets of group B were continuously injected with saline. Peak pressure (Ppk) of the airway was measured before CPB (T1), at the time releasing aortic cross-clamp,and 5 min (T3), 20 min (T4), 40 min (T5), 60 min (T6) after CPB. The blood gases, neutrophils count and TNF-α, IL-8, IL-6 and IL-10 levels were measured at T1, T3, and T6. Lung tissue was collected to measure the wet to dry weight ratio (W/D). The morphologic changes of the lung were also studied. Results At T3, TNF-α, IL-6, and IL-8 levels, Ppk and W/D ratios of group A were significantly lower than those of group B 33.38 ± 9. 71 pg/ml vs 46. 09 ± 12. 12 pg/ml, 27. 84 ±11. 96 pg/ml vs 40. 99 ± 7. 94 pg/ml, 16. 57 ± 1.51 mmHg vs 23. 00 ± 2. 00 mmHg, 0. 21 ± 0. 03 vs 0. 27 ± 0. 04,respectively). At T3, IL-10, oxygenation index, and alveolar-arterial oxygen ratio of group A were significantly higher than those of group B (37. 88 ± 7. 79 pg/ml vs 27. 62 ± 11. 53 pg/ml, 463. 05 ±40. 50% vs 382. 62 ± 80. 01 %, 0. 75 ± 0. 10 vs 0. 56 ± 0. 12). At T6, the neutrophil sequestration,IL8 level, and alveolar-arterial oxygen ratio of group A were significantly higher than those of group B (0. 48 ± 0. 21 vs 0. 77 ± 0. 29, 24. 94 ± 14. 24 pg/ml vs 40. 99 ± 7. 94 pg/ml, 0. 76 ± 0. 07 vs 0. 60 ±0. 07). Lung morphology study also showed group A had less injury. Conclusions Sodium nitroprusside protects lung from injury by suppressing inflammation on piglets with cardiopulmonary bypass.     

脓毒症患儿营养状况的评估

Objective To investigate the severity of infection which is related with serum albumin,cytokines(IL-6、IL-8 and TNF-α)and the concentration of amino acids,it can be helpful to early find malnutrition in sepsis children and provide theories for nutrition support.Methods This prospective study was performed on hospitalized children who were classified as sepsis group(n = 52)and severe sepsis group(n =41).Control group included 300 healthy children.The serum albumin,cytokines(IL-6,IL-8 and TNF-α)and the concentration of amino acids in different groups were measured before the nutrition support.Results Severe sepsis group were all with hypoproteinemia.The concentration of IL-6,IL-8 and TNF-α in severe sepsis group was(193.95±74.11)ng/L、(481.33±186.58)ng/L、(21.00±9.43)ng/L respectively,which were significantly higher than those of sepsis group and control group(P ＜0.01).The concentration of aspartic acid,argine and glycine in severe sepsis group was(23.6±8.5)μmol/L、(6.1±4.7)μmol/L、(101.4± 60.6)μmol/L respectively,which were significantly lower than those of sepsis group and control group(P ＜ 0.01).Conclusion The concentration of aspartic acid,argine and glycine which influence immunologic responses was significantly lower in severe sepsis group with hypoproteinemia,so early nutritional support can improve clirtical outcome.     

肾上腺素对内毒素致大鼠肠道损害的保护作用

目的 探讨肾上腺素对内毒素(lipopolysaccharide,LPS)所致大鼠肠道损害的保护作用及其作用机制.方法 50只SD大鼠随机分为5组(每组10只):对照组:大鼠静脉输注0.9％生理盐水24 ml/(kg·h);LPS组:大鼠静脉注射LPS 6m/kg后,静脉输注生理盐水2.4 ml/(kg·h);低、中和高剂量肾上腺素组:大鼠静脉注射LPS 6 mg/kg后,分别静脉输注肾上腺素0.12 μg/(kg·min)、0.3μg/(kg·min)和0.6μg(kg· min).在LPS注射前、注射后2h和注射后6h3个时点取血,检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10水平,并在24h观察肠道的组织病理学变化.结果 LPS组大鼠在LPS注射后2h血清TNF-α浓度为(1164±145) ng/L,IL-1β浓度为(521±68)ng/L,IL-10浓度为(303±20) ng/L,较对照组均明显升高(P＜0.05).病理结果显示,LPS组小肠黏膜充血、水肿、出血及炎症细胞浸润,上皮细胞坏死、脱落.高剂量肾上腺素组2h血清TNF-α浓度为(576±105) ng/L,2h和6h的IL-10浓度分别为(424±29) ng/L和(24.5±14) ng/L,与LPS组相比血清TNF-α水平明显降低(P＜0.05)且IL-10水平明显升高(P＜0.05),但IL-1β水平无明显变化(P＞0.05).高剂量肾上腺素组大鼠肠道病理损伤明显减轻.中、低剂量肾上腺素组各时间点血清细胞因子水平与LPS组比较,差异无统计学意义(P＞0.05),未见肠道病理损害减轻.结论 肾上腺素可以通过抗炎作用减轻LPS素诱导的肠道损害.     

Clinical application of a Kirschner wire assisted double - hook water - injection hernia needle in complicated pediatric oblique inguinal hernia北大核心CSCD

Objective To explore the clinical value of single -hole laparoscopic percutaneous extraperitoneal closure operation using a Kirschner wire assisted double - hook water - injection hernia needle in treating complicated pediatric oblique inguinal hernia. Methods The clinical data of 366 children with oblique inguinal hernia treated in the Department of Urology Surgery, Children's Hospital of Nanjing Medical University from December 2020 to October 2021 were retrospectively analyzed. According to the surgical methods, the children were divided into the ordinary crochet needle group and the Kirschner wire assisted group. Children treated by a single - port laparoscopic double hook water -injection hernia crochet needle (309 cases) were classified into the ordinary crochet needle group. Children treated by a single - port laparoscopic Kirschner wire assisted double hook water - injection hernia crochet needle (57 cases) were included in the Kirschner wire assisted group. The independent sample t - test and rank sum test was used to compare the relevant clinical indicators between the two groups. Results Compared with the ordinary crochet needle group, children in the Kirschner wire assisted group were younger at surgery [(2. 87 ± 1. 88) years vs. (4. 91 ±2. 39) years] and had larger hernia sacs [17 303.89(8 622.49, 37 295.42) mm3 vs. 9 650.97(3 849.24, 17 539.51) mm3]. The differences in the age at surgery and hernia sac volume were statistically significant (t - 5. 407, Z - 4. 218;all P <0. 001). There was no significant difference in body mass index between the 2 groups (P > 0. 05). Taking hernias with sac volume > 10 000 mm as huge hernias, there were 70. 18% (40/57 cases) and 47. 25% (146/309 cases) of huge hernias in the Kirschner wire assisted group and the ordinary crochet needle group, respectively. The overall operation time of the Kirschner wire assisted group was significantly longer than that of the ordinary crochet needle group [(20(15, 20) min vs. 15 (15, 20) min] (Z - 2. 842, P < 0. 05). However, the operation time for huge oblique hernias with sac volume > 10 000 mm was not statistically significant between the 2 groups (P >0. 05). No recurrence in both groups was found during 6-1 6 months of follow - up. Conclusions For complicated oblique inguinal hernia in children with a huge hernia or obvious retroperitoneal folds at the internal ring and heavy scar adhesion between the hernia sac and abdominal wall, the insertion of a Kirschner wire can help the hernia crochet needle to traverse the vas deferens and spermatic cord vessels smoothly. As a single port laparoscopic operation, the Kirschner wire assisted hernia crochet needle requires no addition of trocar holes and leaves only a small surgical scar. With good feasibility and safety, it is applicable for clinical popularization. © 2022 Chinese Journal of Applied Clinical Pediatrics. All rights reserved.     

急性脑损伤患儿下丘脑促肾上腺皮质激素释放因子水平的变化

Objective To explore the changes of corticotropin releasing factor (CRF) levels secreted by hypothalamus neuron in children with acute brain injury. Methods Fifty-one intracranial-infection children with brain injury and 11 intracranial-noninfection children with brain injury were chosen from pediatric intensive care unit of our hospital. Severities of their brain damage were evaluated by Glasgow score,and CRF level in cerebrospinal fluid (CSF) and serum TNF-α and IL-6 levels were measured by radioimmunoassay. Results There was no significant difference of Glasgow scores between the intracranial infection group and intracranial-noninfection group ( P = 0. 302 6 ), CSF CRF level of intracranial infection group was significantly lower than that of intracranial-noninfection group ( P ＜ 0. 01 ), serum TNF-α and IL-6 levels of intracranial infection group were significantly higher than those of intracranial-noninfection group ( P ＜ 0. 01,P ＜0. 001 ). As comparing to the children with Glasgow score of 6 ～ 7, the levels of CSF CRF and serum TNF-α and IL-6 in children with Glasgow score of 4 ～ 5 were significantly increased ( P ＜ 0. 05, P ＜ 0. 001 ).Conclusion CSF CRF level of the children with acute brain injury is changing, which may be concerned with the secretion of hypothalamus CRF neuron stimulated by TNF-α, IL-6 and hypoxia stress in children with brain injury.     

Changes of B cell - activating factor and a proliferation - inducing ligand in serum of children with Henoch -Schonlein purpura nephritis北大核心CSCD

Objective To investigate the changes of B cell - activating factor (BAFF) and a proliferation -inducing ligand (APRIL) in serum of children with Henoch - Schonlein purpura nephritis (HSPN), and to explore their role in the pathogenesis of children HSPN. Methods A total of 28 children with HSPN who were before treatment were selected in Department of Pediatrics Nephrology and Rheumatology,Shengjing Hospital of China Medical University from November 2017 to August 2018. Sixteen children with Henoch - Schonlein purpura were selected as HSP group, and 20 healthy children were selected as healthy control group. Followed the HSPN guideline to cure the patients for 6-8 weeks. The clinical data were collected. Serum levels of BAFF and APRIL were measured by adopting enzyme -linked immunosorbent assay (ELISA). Results (1) Changes of serum BAFF level: the serum levels of BAFF in HSPN children were significantly lower than those in the HSP group and the healthy control group [HSPN group (0. 652 ± 0.360) |jLg/L,HSP group (1.276 ±0.459) |jig/L, healthy control group (1. 285 ± 0. 299) |jLg/L, F = 17. 519,P = 0.000]. Moreover, the serum levels of BAFF in before treatment were significantly lower than those in after treatment [before treatment (0. 652 ± 0. 360) |JLg/L, after treatment (0. 860 ±0. 262) |JLg/L, P < 0. 05). However, there were no significant di-fferences in the serum levels of BAFF between HSP group and healthy control group (P >0.05). (2)Changes of serum APRIL level: the serum levels of APRIL in HSPN and HSP children were both significantly higher than those in healthy control group,but there were no marked differences between the 2 groups [HSPN group (2.285 ±1.015) |JLg/L, HSP group (2.609 ±1.264) |jig/L, healthy control group (1.677 ±0. 118) |JLg/L,F =3. 647,P =0. 016]. There were no significant differences in the serum levels of APRIL between before treatment and after treatment [before treatment (2. 285 ±1.015) |JLg/L, after treatment (2. 042 ± 0. 695) |Jig/L, P > 0. 05]. (3) Pearson correlation analysis results showed that the serum levels of BAFF were negatively correlated with 24 h urinary protein, urinary microalbumin, and urine red blood cell count (r = -0. 587, -0.608, -0.515,all P <0. 05). The serum levels of APRIL were positively correlated with serum IgA(r = 0. 588,P < 0. 05). Conclusions The level of serum BAFF decreased and APRIL increased in children with HSPN, which was related to the degree of renal involvement. It suggests that BAFF and APRIL may be related to the pathogenesis of HSPN in children. © 2019 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury北大核心CSCD

Objective To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). Methods A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Results Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF- α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Conclusions Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI. © 2023 Xiangya Hospital of CSU. All rights reserved.     

宫内窘迫与产时窒息对新生儿甲状腺功能的不同影响

Objective To investigate the different influences of pre-and/or postnatal hypoxia on the thyroid function of newborns. Methods Newborn infants of fetal hypoxia and/or birth asphyxia diagnosed and treated in pediatric department of Tianjin Medical University Genera] Hospital during last 5 years ,were assigned into intrauterine distress group (group B,n =87) ,birth asphyxia group (group C,n =36) and both of birth asphyxia and intrauterine distress group (group D,n = 75 ). Normal neonates born during the same period served as control group( group A,n =30). Blood concentrations of T3 ,T4 and TSH were detected by radioimmunoassay. Results The serum levels of T3 ,T4 and TSH in A,B,C,and D groups were (0. 86±0. 22) μg/L, (0. 62±0.21)μg/L,(0. 46±0. 19)μg/L,(0. 54±0. 19)μg/L; (125. 13±36.37)μg/L, (107.46±32.21)μg/L,(74.60±26.52)μg/L, (102.23±30.29) μg/L; (6.28±1.96) μg/L, (4.91±1.69) mIU/L, (8.66±2. 00) mIU/L, (5. 64±1.17 mIU/L). There were significant differences among the 4 groups ( P < 0. 01 ). As compared to A group,the serum T3 and T4 concentrations of B ,C and D groups were significantly decreased (P <0. 01 ,P <0. 05 ). No difference of TSH concentrations was found between A and D groups( ( P > 0. 05),but there was significant decrease in B group and significant increase in C group( P <0. 01 ). Conclusion Preand postnatal hypoxia results in decreases of T3 and T4 values,it is likely that newborns of intrauterine distress have decreased TSH, whereas those of birth asphyxia have increased TSH.     

肾上腺素对内毒素血症大鼠早期炎症因子及急性肺损伤的影响

目的：探讨肾上腺素对内毒素( lipopolysaccharide,LPS)所致大鼠肺损伤的保护作用及其作用机制。方法30只SD大鼠随机分为3组(每组10只)：正常对照组大鼠静脉输注生理盐水2．4 ml/( kg·h);LPS组大鼠静脉注射LPS 6 mg/kg后,静脉输注生理盐水2．4 ml/( kg·h);肾上腺素组大鼠静脉注射LPS 6 mg/kg后,静脉输注肾上腺素0．6μg/( kg·min)。在LPS注射后2 h和6 h通过心导管抽血,ELISA法检测血清肿瘤坏死因子( TNF)-α、白细胞介素( IL)-6和IL-10水平,并在6 h处死大鼠取肺脏组织,分别予肺组织含水量检测,HE染色观察肺组织病理学变化,以及ELISA法检测肺泡灌洗液(BALF)内TNF-α、IL-6和IL-10水平。结果(1)与正常对照组肺含水量(70．19%±5．87%)相比,LPS组肺含水量(85．24%±5．87%)明显升高( P <0．05),与 LPS 组相比,肾上腺素组肺含水量(78．00%±6．41%)明显降低(P<0．05)。(2)病理观察结果显示,LPS组大鼠肺泡隔内毛细血管充血、水肿及炎症细胞浸润,少部分肺组织可见肺不张及肺泡内水肿、出血。肾上腺素组大鼠肺病理损伤较LPS组明显减轻。(3)与LPS组相比,肾上腺素组各时点血清TNF-α及IL-6水平明显降低(P<0．05), IL-10水平明显升高(P<0．05)。(4)与LPS组相比,肾上腺素组大鼠BALF中TNF-α水平降低[(78±9)ng/L vs.(102±16) ng/L],IL-6水平降低[(268±42) ng/L vs.(347±50) ng/L],IL-10水平升高[(210±23)ng/L vs.(146±34) ng/L](P<0．05)。结论肾上腺素可减轻LPS诱导的急性肺损伤,其保护作用可能与降低TNF-α、IL-6水平,升高IL-10水平有关。     

2009甲型H1N1流感患儿免疫功能改变初探

目的 探讨2009甲型H1N1流感(以下简称"甲流")患儿免疫功能及可能的免疫发病机制.方法 深圳市儿童医院2009年11月1日-2010年1月10日甲流住院患儿60例,轻症35例(轻症肺炎),重症25例(重症肺炎或甲流相关性脑病,死亡3例),同年龄正常对照组20例.采用real-time PCR、流式细胞术及ELISA检测外周血单个核细胞胞浆模式识别受体(PRRs)维甲酸诱导基因I/黑色素瘤分化相关基因5(RIG/MDA5)、胞膜PRRs Toll样受体(TLRs)分子及其信号途径传导分子、细胞因子/趋化因子及负性调节因子变化;T、B及NK细胞凋亡及凋亡相关基因TRAIL和CASPASE-3表达.结果 (1)甲流患儿RIG/MDA5表达、TLR2、TLR4表达明显高于正常对照组[TLR2(9.69±3.15)×10-2vs.(3.96±0.83)×10-2,t=10.16,P＜0.05;TLR4(10.23±2.85)×10-2vs.(7.46±2.18)×10-2,t=3.76,P＜0.05],以重症甲流患儿增高为著,RIG/MDA5表达增高最为明显;TLRs途径信号传导分子MyD88、TRAM等表达明显高于轻症甲流患儿.(2)甲流患儿CD3+[(1.22±0.38)×109/Lvs.(3.59±1.10)×109/L,t=9.21,P＜0.05]、CD4+、CD8+T细胞及NK细胞绝对计数明显低于正常对照组,B细胞无明显改变.(3)轻症甲流患儿TNF-α、IL-6、IL-1β等炎症细胞因子血浓度或基因高于正常对照组,重症患儿炎症细胞因子TNF-α[(6.42±1.76)×10-2vs.(9.05±2.51)×10-2,t=4.55,P＜0.05]明显低于正常对照组.IFN-α/β表达持续高于正常对照组,尤以重症甲流患儿为著;IFN-I诱导基因IP-10[(20.52±6.09)×10-2vs(1.18±0.34)×10-2,t=18.74,P＜0.05]、RANTES或iNOS轻症患儿表达高于正常对照组,重症患儿表达则趋于减少.(4)甲流患儿CD3+[(32.90±7.66)%vs.(20.21±6.58)%,t=6.21,P＜0.05]、CD4+、CD8+T细胞、NK细胞凋亡高于正常对照组,以重症患儿更为显著.凋亡相关基因TRAIL和CASPASE-3表达明显高于正常对照组.(5)重症患儿PRRs负性凋节因子SOCS1、SOCS3、IRAK-M、TRAF4及FLN29表达明显高于轻症患儿,抗炎细胞因子IL-10及IL-10/TNFα比值随病情加重增高.结论 甲流患儿机体免疫功能紊乱,轻症患儿处于全身免疫激活状态,重症患儿同时存在免疫激活/免疫抑制反应.     

持续去甲肾上腺素输注对早期脓毒症大鼠肾脏的保护作用及其机制研究

目的探讨持续去甲肾上腺素输注对早期脓毒症大鼠肾脏是否存在保护作用及其可能机制。方法30只SPF级健康雄性SD大鼠采用随机数字表法随机分为5组（6只／组）。对照组：腹腔注射生理盐水,并开始持续输注生理盐水1ml／h。脂多糖（lipopolysaccharide,LPS）组和低剂量、中剂量和高剂量去甲肾上腺素组：腹腔注射LPS10mg／kg,LPS组持续输注生理盐水1ml／h,低、中、高剂量组分别持续输注0．06、0．30、0．60μg／（kg·min）去甲肾上腺素溶液1ml／h,均持续输注24h处死大鼠。检测2、6h大鼠血清炎症因子肿瘤坏死因子（tumor necrosis factor,TNF）-α、白细胞介素（interleukin,IL）-1β、IL-6及IL-10水平,24h大鼠血清C-反应蛋白（CRP）、肌酐（Cr）和尿素氮（BUN）水平,膜电位和氧化应激相关指标,电镜观察肾脏线粒体肿胀程度,显微镜观察肾脏病理变化。结果与对照组比较,2hLPS组TNF—α浓度为（2203．3±1028．7）pg／ml、IL-1β（2214．5±457．0）pg／ml、IL-6（7784．7±248．2）pg／ml及IL-10（1076．1±368．4）pg／ml,均明显升高（P〈0．05）;24hCRP（0．35±0．24）mg／L,Cr（30．8±11．5）μmol／L,BUN（7．7±1．8）mmol／L,一氧化氮（1057．4±172．9）μmol／gprot,均明显升高（P〈0．01）,肾脏线粒体膜电位0．0464±0．0185,明显下降（P〈0．01）。与LPS组比较,2h低剂量组TNF-d浓度为（506．8±301．7）pg／ml、IL-1β（415．6±178．0）pg／ml及IL-α（381．7±171．0）pg／ml,均明显下降（P〈0．05）,24hBUN下降为（5．2±1．4）mmol／L（P〈0．05）,线粒体膜电位上升为0．3474±0．1526（P〈0．05）;2h中剂量组TNF-α浓度为（323．9±227．9）pg／ml、IL-1β（700．0±246．2）pg／ml,IL-10（282．6±134．4）pg／ml,均明显下降（P〈0．05）,24hCRP下降为（0．17±0．08）mg／L（P〈0．05）,线粒体膜电位上升为0．3775±0．1437（P〈0．05）;高剂量组2hTNF-α浓度为（378．7±89．8）pg／ml、IL-1β（945．7±264．4）pg／ml,明显下降（P〈0．05）,24hCRP（0．19±0．12）mr／L、Cr（23．2±3．4）μmol/L均明显下降（P〈0．05）。电镜观察显示LPS组线粒体包膜模糊及基质空泡化、凝固,显微镜观察显示LPS组肾组织间隙水肿,单核-巨噬细胞浸润,肾小球皱缩,肾小管上皮细胞肿胀、空泡变性等,中剂量组病理损伤明显减轻。结论持续去甲肾上腺素输注对早期脓毒症大鼠肾脏有一定的保护作用,其机制与降低炎症因子风暴的水平、减轻氧化应激损害、改善线粒体功能相关。     

新生儿期至青春期血中肉碱和酰基肉碱的变化

目的 用串联质谱测定不同年龄儿童血中游离肉碱和各种酰基肉碱浓度,为诊断肉碱缺乏和各种有机酸和脂肪酸代谢病奠定基础.方法 研究对象是围产期新生儿1376例,大于1周的新生儿49例,小于1岁的婴幼儿64例,1～15岁儿童401例.围产期新生儿是无选择的产院出生儿,包括了少量早产儿和低出生体重儿.其余主要是排除了发热、腹泻、肝病、严重疾病等影响脂肪代谢的门诊小手术的体检儿童.用非衍生法前处理滤纸血片,串联质谱测定其中游离肉碱和30种酰基肉碱浓度.结果 游离肉碱(C0)、短链酰基肉碱(C2、C3、C4、C5)、中链酰基肉碱(C6、C8、C 10)及其烯酰基、羟基、二酰基肉碱和总肉碱水平新生儿阶段较低,1～3个月时最高,之后降低,2～15岁在相同水平维持.长链酰基肉碱(C12、C14、C16、C18)及其烯酰基肉碱、羟基酰基肉碱及其总和新生儿阶段最高,逐渐降低,2～15岁在相同水平维持.游离肉碱浓度(23.387±7.702)μmol/L,(30.064±8.252)μmol/L,(25.021±6.630)μmol/L,总长链酰基肉碱浓度(4.998±1.557)μmol/L,(2.854±0.821)μmol/L,(2.459±0.553)μmol/L,肉碱酰基肉碱总浓度(43.497±12.632)μmol/L,(49.013±12.497)μmol/L,(39.656±9.257)μmol/L在新生儿组、小于1岁组和大于1岁组差异有统计学意义(P＜0.01).围产期新生儿男婴组肉碱(24.115±7.715)μmol/L和肉碱和酰基肉碱总和(43.65±5.252)μmol/L分别高于女婴(22.696±7.246)μmol/L和(41.90±5.038)μmol/L(P＜0.05).新生儿组游离肉碱占总肉碱比值(54.0%±7.1%)明显小于非新生儿组(62.1%±6.1%,P＜0.05),而长链(33.5%±6.0%)、中链(1.3%±0.3%)和短链脂酰基肉碱(11.6%±2.5%)与总肉碱比值分别高于非新生儿组(30.1%±4.9%;0.9%±0.6%;6.5%±2.3%,P＜0.05).结论 1岁以内血中肉碱和酰基肉碱水平和构成变化较大,在评价肉碱营养状态和诊断有机酸和脂肪酸代谢病时要考虑年龄因素.围产期新生儿男婴肉碱和酰基肉碱略高于女婴.     

急性脑损伤患儿下丘脑促肾上腺皮质激素释放因子水平的变化

目的 探讨急性脑损伤患儿下丘脑神经元促肾上腺皮质激素释放因子(CRF)分泌水平的变化.方法 选择我院儿科监护病房51例颅内感染和11例非颅内感染脑损伤患儿为研究对象,用Glasgow评分对其脑损伤严重程度进行评估,用放射免疫法测定脑脊液中CRF水平与血清中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平.结果 颅内感染组和非颅内感染组患儿的Glasgow评分差异无统计学意义(P=0.302 6),颅内感染组患儿的脑脊液中CRF浓度低于非颅内感染组(P＜0.01),TNF-α、IL-6水平高于非颅内感染组(P＜0.01,P＜0.001).与Glasgow评分为6～7分的患儿相比,Glasgow评分为4～5分的患儿脑脊液CRF及血清TNF-x和IL-6水平显著增加(P＜0.05,P＜0.001).结论 颅内感染组和非颅内感染组患儿脑脊液中CRF水平是变化的,这可能与TNF-α、IL-6和低氧应激刺激脑损伤患儿下丘脑CRF神经元分泌有关.

Abstract：

Objective To explore the changes of corticotropin releasing factor (CRF) levels secreted by hypothalamus neuron in children with acute brain injury. Methods Fifty-one intracranial-infection children with brain injury and 11 intracranial-noninfection children with brain injury were chosen from pediatric intensive care unit of our hospital. Severities of their brain damage were evaluated by Glasgow score,and CRF level in cerebrospinal fluid (CSF) and serum TNF-α and IL-6 levels were measured by radioimmunoassay. Results There was no significant difference of Glasgow scores between the intracranial infection group and intracranial-noninfection group ( P = 0. 302 6 ), CSF CRF level of intracranial infection group was significantly lower than that of intracranial-noninfection group ( P ＜ 0. 01 ), serum TNF-α and IL-6 levels of intracranial infection group were significantly higher than those of intracranial-noninfection group ( P ＜ 0. 01,P ＜0. 001 ). As comparing to the children with Glasgow score of 6 ～ 7, the levels of CSF CRF and serum TNF-α and IL-6 in children with Glasgow score of 4 ～ 5 were significantly increased ( P ＜ 0. 05, P ＜ 0. 001 ).Conclusion CSF CRF level of the children with acute brain injury is changing, which may be concerned with the secretion of hypothalamus CRF neuron stimulated by TNF-α, IL-6 and hypoxia stress in children with brain injury.     

足月新生儿肺通气功能肺力学改变与心功能的关系

目的 探讨足月新生儿肺通气功能、肺力学及心功能的变化规律及其相关性.方法 200例足月儿,据日龄分为A、B、C、D四组,其日龄分别为0～24 h、～72 h、～1周、～28 d.采用德国耶格公司Master screen Paed型肺功能仪测定肺通气功能及单次阻断法测定气道阻力、肺顺应性.肺功能主要参数:潮气量(TV)、分钟通气量(MV)、呼吸系统顺应性(Crs)、呼吸系统阻力(Rrs).采用美国SonoSite 180 PLUS彩色多普勒超声诊断仪检测心功能.心功能主要参数:每搏输出量、心输出量(CO).结果 A、B、C、D四组的TV分别为20.2±3.8、21.1±3.7、22.3±4.5、23.9±4.9(ml),C、D组TV与A组比较,D组TV与B组比较,差异有显著性(P＜0.05).Rrs、Crs组间差异无显著性(P＞0.05).A、B、C、D四组CO分别为0.93±0.23、0.93±0.23、1.02±0.21、1.08±0.27(L/min),D组CO与A、B组比较差异有显著性(P＜0.05).CO与Rrs呈负相关(r=-0.16,P＜0.05),与MV、TV、Crs呈正相关(r分别为0.50、0.54、0.13,P均＜0.05).结论 足月儿生后72 h后肺通气功能趋于稳定.左心输出量于生后1周明显增加.肺通气功能和肺力学指标是影响心功能的因素.

Abstract：

Objective To investigate the dynamic change and correlation of the pulmonary ventilative function, mechanic and cardiac function in the term infants. Methods Twenty hundred term infants were divided into A 、B 、C and D groups by age which was 0 ～ 24 h, ～ 72 h, ～ 1 w and 28 d respectively. The lung ventilative and mechanical function were measured respectively by using techniques of tidal breathing flow-volume loop(TBFVL)and the single occlusion. The Master screen Paed-lung function devices of Germanic JAEGER Co. was be used in this study. The parameter of pulmonary function including minute volume(MV) ,tidal volume (TV), respiratory system compliance(Crs) and respiratory system resistance (Rrs). The cardiac function were measured by using SonoSite 180 PLUS color Doppler ultrasonic diagnostic apparatus. The main parameter of cardiac function including cardiac output(CO) and stroke volume(SV). Results The TV of A, B ,C and D group were 20. 2 ± 3.78,21. 1 ± 3.71,22. 3 ± 4. 48 and 23. 9 ±4.90 (ml)respectively, the TV of C and D group were higher than that of A group, and the TV of D group was higher than that of B group (P ＜ 0. 05).There were no significantly difference of Crs, Rrs among A, B, C and D group(P ＞ 0. 05). The CO of A,B,C and D group were 0.93 ±0. 23,0.93 ±0.23,1.02 ±0.21 and 1.08 ±0.27 (L/min) ,the CO of D group was higher than that of A and B groups (P ＜ 0. 05). The CO was negative correlation with Rrs (r = - 0. 16,P ＜ 0. 05) and positive correlation with MV、 TV、 Crs (r was 0. 50、 0. 54、0. 13 respectively, P ＜ 0. 05).Conclusion The lung ventilative function is mature gradually with increasing age. The cardiac output has been obviously improved for postnatal 1 week in the term infants. The pulmonary ventilative function and mechanic parameter are important effective factors of cardiac function.     

克罗恩病和健康儿童血清细胞因子水平的病例对照研究

目的 观察克罗恩病（CD）患儿血清细胞因子水平,探讨细胞因子水平紊乱在儿童克罗恩病发病中的作用。 方法 纳入2013年1月至2015年12月在温州医科大学育英儿童医院（我院）儿内科住院的确诊CD患儿（病例组,根据CD活动度分为不同亚组）和同期在我院门诊体检的健康儿童,采用流式分析技术检测晨起空腹静脉血血清中IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ和IL-17A的水平。 结果 病例组32例,男18例,女14例,年龄（8.5±4.3）岁,其中CD轻度活动亚组12例,CD中重度活动亚组20例;对照组30名,男18名,女12名,年龄（10±3.5）岁。病例组和对照组年龄、性别比较差异无统计学意义（P>0.05）。病例组患儿血清IL-2、IL-4、IL-6、TNF-α和IL-17A水平高于对照组,血清IL-10和IFN-γ水平低于对照组,差异均有统计学意义（P＜0.05）。此外,根据儿童CD活动指数（PCDAI）评分为中重度活动亚组患儿的血清IL-2、TNF-α和IL-17A水平高于轻度活动亚组患儿,差异有统计学意义（P＜0.05）。 结论 与健康儿童相比,CD患儿存在明显的免疫相关细胞因子水平变化,而且疾病活动度不同其细胞因子水平亦有差异,提示细胞因子水平紊乱在儿童CD发病及病情的发展中有重要作用。     

IL-13和TNF-α在肺炎支原体肺炎儿童血清中的表达及意义

目的：观察白细胞介素13（interleukin-13,IL-13）和肿瘤坏死因子α（tumor necrosis factor alpha,TNF-α）在小儿肺炎支原体肺炎中的变化。方法:酶联免疫方法检测40例肺炎支原体肺炎伴喘息患儿、40例肺炎支原体肺炎不伴喘息患儿、其他病原菌感染肺炎40例（普通肺炎组）及40例正常对照组儿童的血清IL-13和TNF-α的浓度。结果:肺炎支原体肺炎患儿血清IL-13、TNF-α的水平高于正常对照组及普通肺炎组;肺炎支原体肺炎伴喘息患者的IL-13、TNF-α的水平分别为214.6±67.2 ng/L,0.55±0.13 ng/L,高于不伴喘息者（189.6±52.1 ng/L, 0.42±0.16 ng/mL）,差异均有显著性（P<0.01）。结论：IL-13、TNF-α浓度增高可能在小儿肺炎支原体肺炎导致喘息样发作中起重要作用。［中国当代儿科杂志,2010,12（4）：275-277］