SURF1-associated Leigh syndrome: a case series and novel mutations

Leigh syndrome (LS) is a mitochondrial disease that typically presents in infancy with subacute neurodegenerative encephalopathy. It is genetically heterogeneous, but mutations in the complex IV assembly genes, particularly SURF1, are an important cause. In this study, SURF1 gene was sequenced in 590 patients with clinical suspicion of LS, complex IV deficiency, or clinical features of mitochondrial disorders. We identified 21 patients with clinical features of LS who are either homozygous or compound heterozygous for SURF1 mutations. Twenty-two different mutations were identified, including 13 novel mutations. Of the 42 mutant alleles, 36 (86%) are null mutations (frameshift, splicing, or nonsense) and 6 (14%) are missense. We have also reviewed the previously reported SURF1 mutations and observed a clustering of mutation in exon 8 of SURF1, suggesting a vital function for this region. Although mutations in SURF1 have been mainly associated with typical LS, five of the patients in this report had an atypical course of LS. There is no definite genotype-phenotype correlation; however, frameshift mutations resulting in protein truncation closer to the C-terminus may carry a better prognosis.     

Copy number aberrations in combined hepatocellular carcinoma and cholangiocarcinoma

Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is a rare liver cancer which shares unequivocal features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). A greater awareness of genetic relationship between HCC and CC components is limited. To help characterize this rare liver neoplasm, we described clinicopathologic features and evaluated copy number (CN) changes in this study. A total of 13 cases of CHC were collected. Four paired HCC and CC components from four cases were first subject to genome-wide analysis. Nine target genes were subsequently selected for further analysis using quantitative polymerase chain reaction. The paired HCC and CC components in each case had a concordant trend of CN gain or loss in these nine genes. However, the magnitude of concordant CN gain or loss was different. There were significant differences of CN copies between HCC and CC in each case. We demonstrate genetic divergence between HCC and CC components in CHC.     

Calcium phosphate drug nanocarriers with ultrahigh and adjustable drug-loading capacity: One-step synthesis, in situ drug loading and prolonged drug release

Calcium phosphates (CPs) are regarded as the most biocompatible inorganic biomaterials; however, they are limited in the drug-delivery applications, especially for hydrophobic drugs. Achieving high drug-loading capacity and a controllable drug-release property are two main challenges. In this study we report a strategy for the preparation of novel drug delivery systems based on a concerted process in which the formation of the CP nanocarriers and the drug storage are accomplished in one step in mixed solvents of water and ethanol. The key advantage of this strategy is that the formation of CP nanocarriers and in situ loading of the drug occur simultaneously in the same reaction system, which makes it possible to achieve ultrahigh drug-loading capacity and prolonged drug release due to ultrahigh specific surface area and numerous binding sites of the CP nanocarriers. A series of hydrophobic drug-delivery systems with adjustable drug-loading capacities and drug-release rates have been successfully synthesized. In addition, the drug-release kinetics of the as-prepared drug-delivery systems have been found in which the cumulative amount of drug release has a linear relationship with the natural logarithm of release time. FROM THE CLINICAL EDITOR: Calcium phosphates (CPs) are highly biocompatible inorganic biomaterials with thus far limited drug-delivery applications. This study reports the preparation of a novel drug delivery system where the formation of CP nanocarriers and in situ loading of the drug occur simultaneously in the same reaction, enabling ultra-high drug-loading.     

Association of T-helper cell cytokine level with age in patients with biliary atresia: a preliminary study

Background

The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA.

Methods

Twenty-eight patients with BA were divided into three groups according to their age (<?2 months, 2–3 months, and?≥?3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients preoperatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1.

Results

The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged?≥?3 months were significantly higher than those in patients aged?<?2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expression levels in the liver tissue of patients with BA.

Conclusions

The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient’s age into consideration.

     

Clinical characteristic comparison of low birth weight and very low birth weight preterm infants with neonatal necrotizing enterocolitis: a single tertiary center experience from eastern China

Purpose

This study aims to understand the clinical characteristics of preterm neonatal necrotizing enterocolitis (NEC) to improve the medical management level.

Methods

The clinical characteristics of preterm NEC infants with low birth weight (LBW, ≥?1500 g) and very low birth weight (VLBW, <?1500 g) were compared. Then, clinical information, including demographics, surgical interventions and morbidity, were collected.

Results

A total of 149 preterm NEC infants (60 with VLBW and 89 with LBW) were enrolled. Their median birth weight and gestational age were 1600 g and 31 weeks, respectively. Respiratory support and surfactant therapy were more frequent in VLBW infants (90% vs. 38% and 75% vs. 21.3%) than in LBW infants. In addition, 70.5% of these infants were fed by formula before the NEC occurred. Prematurity-associated morbidities were significantly higher in VLBW infants. Furthermore, 12.8% of all NEC infants died at discharge, and mortality was more prevalent in VLBW infants (21.7% vs. 6.7%). The most frequently received surgeries were enterostomy (n?=?58), primary anastomosis (n?=?42), and peritoneal drainage (n?=?2). Multifocal, localized and pan-intestinal disease occurred in 77.5%, 19.6% and three infants, respectively. Furthermore, postoperative complications occurred more frequently in VLBW infants.

Conclusion

The overall mortality was 12.8% for infants who had a larger mean gestational age and birth weight, when compared to that in developed countries. Higher rate of formula feeding might be an important risk factor for NEC development. Furthermore, mortality and morbidities, especially nutrition-associated complications, were more frequent in VLBW infants.

     

全身炎症反应综合征患儿中性粒细胞淋巴细胞CD11b表达意义

目的：探讨全身炎症反应综合征（SIRS）患儿血液中性粒细胞、淋巴细胞CD11b表达对诊断和判断病情的意义。方法：用流式细胞术检测36例SIRS患儿血液中性粒细胞、淋巴细胞CD11b表达水平,28例一般感染性疾病,不符合SIRS诊断标准的患儿作为对照组。比较各指标对诊断SIRS的灵敏度、特异度,评价它们对诊断SIRS和判断病情的价值。结果：急性期SIRS组中性粒细胞CD11b表达为（96.7±8.1）%,高于对照组的（85.1±5.1）%,差异有显著性（P＜0.05）。中性粒细胞CD11b＞92.24%为阳性标准,诊断SIRS敏感性和特异性分别为97.2%,92.9%。急性期SIRS组淋巴细胞CD11b表达为(13.4±8.6)%,对照组为（19.2±6.4）%,差异有显著性（P＜0.05）;其中严重脓毒症组淋巴细胞CD11b表达为（7.3±3.0）%,低于非感染SIRS组的（19.3±2.9）%和脓毒症组的(15.9±12.5)%（P＜0.01）。恢复期SIRS组淋巴细胞CD11b表达为（13.35±4.89）%,对照组为（13.8±4.7）%,差异无显著性（P＞0.05）。结论：中性粒细胞CD11b可作为诊断SIRS的可靠指标,淋巴细胞CD11b表达下调可能是SIRS患儿病情加重的信号。［中国当代儿科杂志,2009,11（7）：540-542］     

Serum soluble ST2 is a promising prognostic biomarker in HBV-related acute-on-chronic liver failure

BACKGROUND: The IL-33/ST2 axis is involved in the patho-genesis of many diseases such as autoimmune diseases, cancer, and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure (HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2 (sST2) in HBV-ACLF.METHODS: Serum levels of IL-33 and sST2 in healthy controls (HC, n=18), chronic hepatitis B (CHB, n=27) and HBV-ACLF (n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS: There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1. However, serum sST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a re-verse correlation between serum sST2 level and the survival of HBV-ACLF patients. The level of serum sST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF non-survivors remained at a high level during the same period. Fur-thermore, serum sST2 level was significantly correlated with laboratory parameters and the most updated prognostic scores (CLIF-C OF score, CLIF-C ACLF score and ACLF grades). The receiver operating characteristics curves demonstrated that serum sST2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sST2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF pa-tients with serum sST2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION: Serum sST2 may act as a promising biomark-er to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.     

后房造漏术联合丝裂霉素C应用治疗晚期新生血管性青光眼疗效观察

目的探讨后房造漏术联合丝裂霉素C应用治疗晚期新生血管性青光眼的临床疗效。方法采用巩膜瓣下后房造漏术联合术中使用丝裂霉素C治疗晚期新生血管性青光眼15例(15只眼),术后对眼压、视力、前房、滤过泡形态进行随诊观察分析。结果15例(15只眼)术后经3～24个月观察随访,术前平均眼压(49.23±10.5)mmHg,术后平均(15.6±7.3)mmHg,手术前后有显著性差异(P<0.05);术后视力提高5只眼,不变7只眼;功能性滤过泡占80.00%。结论该术式在眼压控制、滤过泡形成等方面临床效果好,为安全有效的手术方法。