IL13RA2 promotes progression of infantile haemangioma by activating glycolysis and the Wnt/β-catenin signaling pathway

Background:Interleukin 13 receptor subunit alpha 2(IL13RA2)plays an essential role in the progression of many cancers.However,the role of IL13RA2 in infantile haemangioma(IH)is still unknown.Materials and Methods:IL13RA2 expression in IH tissues was analyzed using western blot,qRT-PCR,and immunofluorescence.The role of IL13RA2 in haemangioma-derived endothelial cells(HemECs)was determined following knockdown or overexpression of IL13RA2 using CCK-8,colony formation,apoptosis,wound healing,tubule formation,Transwell,and western blot.Results:IL13RA2 expression was upregulated in IH tissues.IL13RA2 overexpression promoted proliferation,migration,and invasion of HemECs and induced glycolysis,which was confirmed with a glycolysis inhibitor.Specifically,IL13RA2 interacted withβ-catenin and activated the Wnt/β-catenin pathway in HemECs,which were involved in the above-mentioned effects of IL13RA2.Conclusions:These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.

Intralesional corticosteroid injections for infantile hemangioma

Infantile hemangiomas(IHs) are the most common benign soft-tissue tumors in infancy;about 10%–15% of them may result in various complications that require active management. The current first-line treatment for IH is oral propranolol;however, some studies recommend intralesional corticosteroid injections for small, limited, deep, or prominent tumors because of concern regarding serious systemic complications related to propranolol. This review summarizes and analyzes the current clinical studies on corticosteroid injections in IHs, discusses treatment norms, and explores future research directions.

Prenatal ultrasound diagnosis of congenital infantile fibrosarcoma and congenital hemangioma: Three case reports

BACKGROUND Congenital infantile fibrosarcoma(CIF)and congenital hemangioma(CH)have similarities on prenatal ultrasound and are rare.CASE SUMMARY We report 3 cases of fetuses with superficial hypervascular tumors,confirmed by postnatal pathology as CIF(1 case)and CH(2 cases,including 1 in a twin fetus).In Case 1,a mass with a rich blood supply in the fetal axilla was discovered by prenatal ultrasound at 28+0 wk of gestation.The postpartum pathological diagnosis was CIF,the mass was surgically removed,and the prognosis of the child was good.In Case 2,at 23+1 wk of gestation,a mass was discovered at the base of the fetus’s thigh on prenatal ultrasound.The postpartum pathological diagnosis was CH.After conservative treatment,the mass shrank significantly.Case 3 occurred in a twin fetus.At 30+0 wk of gestation,prenatal ultrasound revealed a bulging mass with a rich blood supply on the abdominal wall of one of the fetuses.Three weeks later,the affected fetus died,and the unaffected baby was successfully delivered by emergency cesarean section.The affected fetus was pathologically diagnosed with CH.CONCLUSION Prenatal ultrasound can provide accurate information,such as the location,size and blood supply of a surface mass in a fetus.We found similarities between CIF and CH in prenatal ultrasound findings.Although it is difficult to distinguish these conditions by prenatal ultrasound alone,for superficial hypervascular tumors that rapidly increase in size in a short period,close ultrasound monitoring of the fetus is required to quickly address possible adverse outcomes.

Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test?

BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their occurrence.AIM To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT.METHODS Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure.During each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was monitored.Coronary spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic changes.ACh was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,respectively.Coronary arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group MH.Those who did not occur coronary spasms at any ACh dose were designated as group N.RESULTS Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group MH.Baseline Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.

Mechanism of acupuncture for limb spasm of post-stroke spasticity based on GABA and BDNF/Trkb-KCC2 signaling pathway

Background:To investigate the effects of acupuncture on post-stroke limb spasm model rats and the underlying mechanism.Methods:A total of 50 Sprague-Dawley rats were randomly divided into three groups,Control group(10),Model group(20)and Zhishen Tiaoxing(ZSTX)acupuncture group(20).Middle cerebral artery occlusion was conducted in SD rats to establish post-stroke limb spasm rats,which were treated with ZSTX acupuncture.Behavioral assays were determined by the Narrow ally test,the limb muscle tension was detected by the BL-420S test system,and infarct volume was assessed after the cerebral infarction by 2,3,5-triphenyltetrazolium chloride staining.Heterogeneous neurotransmitterγ-aminobutyric acid(GABA)and its receptors GABAA and GABAB in the cerebral cortex of the infarct area were determined by immunofluorescence assay.The release of Trkb and K-Cl cotransporter isoform 2 was detected by an immunofluorescence double labeling study.Western Blot was utilized to measure the expression of BDNF and Trkb.Results:The results showed that the behavioral assays in post-stroke limb spasm rats were significantly improved by the treatment of ZSTX acupuncture.14 days of ZSTX acupuncture can effectively inhibit muscle tone and decrease Infarct volume,which was measured with BL-420S biological function experiment system and triphenyltetrazolium chloride.Meanwhile,the results of Double-Label Immunofluorescence Assays showed that ZSTX acupuncture improved the expression of GABA,GABAA,GABAB,BDNF,and K-Cl cotransporter isoform 2.Double-Label Immunofluorescence Assays and WB results showed that 14 days ZSTX acupuncture declined the expression of Trkb.Conclusions:Our results suggest that 14 days of ZSTX acupuncture can significantly improve post-stroke limb spasm.Meanwhile,the pathogenesis of post-stroke limb spasm and the efficacy of ZSTX acupuncture involve metabolic pathways of neurotransmitters,and electro-acupuncture can treat post-stroke limb spasm by regulating BDNF/Trkb-KCC2 signaling pathway.

Brain MRI Findings in Infantile Spasm: Outcome Correlations in a Patient Cohort

Background: Infantile spasm is a type of pediatric seizure often associated with a negative prognosis. The aim of this study was to evaluate the role of Magnetic Resonance Imaging (MRI) in categorization and neurodevelopmental outcomes in children with infantile spasm. Materials and Methods: A retrospective study of the clinical charts and MRI findings of infants diagnosed with infantile spasm between December 2007 and February 2014. Results: A total of 26 children (16 males;1.6/1) were included: 8 of unknown etiology and 18 with a genetic/structural-metabolic causes. Unknown etiology cases revealed normal brain MRI in 5/8 (62.5%). In the genetic/ structural-metabolic group, only 2/18 (11.1%) had normal imaging. Abnormal imaging findings significantly correlated with genetic/structural-metabolic infantile spasm which had unfavorable neurodevelopmental outcome. Conclusion: Neuroimaging conveys substantial information to the further categorization of children with infantile spasm, providing not only relevant information of the underlying cause but also the prediction of the neurodevelopmental outcome.

Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.

Infantile hepatic hemangioendothelioma:A clinicopathologic study in a Chinese population

AIM:To investigate whether the clinicopathologic features of infantile hemangioendothelioma(IHE) of the liver in a Chinese population are similar to the features observed in other races.METHODS:The clinical data,radiological findings,histopathological changes and outcome of 12 cases of IHE diagnosed by the Department of Pathology,West China Hospital over the last 10 years were analyzed retrospectively.Immunohistochemical studies were carried out using antibodies against CD31,CD34,Factor Ⅷ,cytokeratin 8 and cytokeratin 18.RESULTS:The 12 patients were aged from fetal to 5 years(three males and nine females).The tumor was presented with different clinical manifestations,mainly as an asymptomatic,palpable,upper abdominal mass,except for the two fetuses who were detected antena-tally by ultrasound.In one patient,this presentation was accompanied by an initial severe pneumothorax.No symptoms of congestive heart failure were present and neither congenital abnormalities nor vascular tumors in the skin or other organs were found.Laboratory abnormalities included leukocytosis(40%),anemia(60%),thrombocytosis(60%),hyperbilirubinemia(16.7%),abnormal liver function(50%) and increased α-fetoprotein(80%).Based on radiological findings and gross specimens,the tumor presented as a solitary lesion or a multifocal space-occupying lesion.The tumor size ranged from 5.0 cm × 3.5 cm × 2.0 cm to 13.8 cm × 9.0 cm × 7.7 cm,and the 0.2-1.1 cm nodules were diffusely distributed within the multifocal tumor.Seven cases were surgically resected,three cases underwent biopsy and the two fetuses were aborted.Histologically,nine cases were classified as typeⅠ and three as type Ⅱ,presenting aggressive morphologic features,immature vessels,active mitosis and necrosis.An inflammatory component,predominantly eosinophilic granulocytes,sometimes obscured the nature of the tumor.Ten patients are alive after a follow-up of 1-9 years.Based on immunohistochemistry,the endothelial cells in all cases were positive for CD31,CD34 and polyclonal factor Ⅷ antigen,whereas the scattered hyperplasia bile ducts were positive for cytokeratin 8 and cytokeratin 18.CONCLUSION:The clinical manifestations of IHE are non-specific.There is no significant correlation between histological type and prognosis.The clinicopathologic features of IHE in Chinese patients may provide a clue to further evidence-based studies.

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment

AIM To investigate the impact of fecal microbiota transplantation(FMT) treatment on allergic colitis(AC) and gut microbiota(GM).METHODS We selected a total of 19 AC infants,who suffered from severe diarrhea/hematochezia,did not relieve completely after routine therapy or cannot adhere to the therapy,and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT,and GM composition was assessed for infants and donors using 16 S r DNA sequencing analysis.RESULTS After FMT treatment,AC symptoms in 17 infants were relieved within 2 d,and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to followup. During follow-up,one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16 S r DNA analysis in ten AC infants,most of them(n = 6) had greater GM diversity after FMT. As a result,Proteobacteria decreased(n = 6) and Firmicutes increased(n = 10) in post-FMT AC infants. Moreover,Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level,Bacteroides(n = 6),Escherichia(n = 8),and Lactobacillus(n = 4) were enriched in some AC infants after FMT treatment,but the relative abundances of Clostridium(n = 5),Veillonella(n = 7),Streptococcus(n = 6),and Klebsiella(n = 8) decreased dramatically.CONCLUSION FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.

Cardiovascular drugs in the treatment of infantile hemangioma

Since the introduction of propranolol in the treatment of complicated infantile hemangiomas(IH) in 2008, other different beta-blockers, including timolol, acetabutolol, nadolol and atenolol, have been successfully used for the same purpose. Various hypotheses including vasoconstriction, inhibition of angiogenesis and the induction of apoptosis in proliferating endothelial cells have been advanced as the potential beta-blockerinduced effect on the accelerated IH involution, although the exact mechanism of action of beta-blockers remains unknown. This has generated an extraordinary interest in IH research and has led to the discovery of the role of the renin-angiotensin system(RAS) in the biology of IH, providing a plausible explanation for the beta-blocker induced effect on IH involution and the development of new potential indications for RAS drugs such as angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the treatment of IH. This review is focused on the current use of cardiovascular drugs in the treatment of IH.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

Topical Propranolol Hydrochloride Gel for Superficial Infantile Hemangiomas

The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected to the topical propranolol hydrochloride gel intervention in Fuzhou General Hospital of Nanjing Military Commands, China. Changes in size, texture, color, peak systolic velocity of the hemangiomas, resistance index and adverse effects were observed. The results were evaluated by using Achauer system, and responses of IHs to pranpronolol were considered scaleⅠ(poor) in 4 patients (17.24%), scaleⅡ(moderate) in 18 patients (24.14%), scale Ⅲ (good) in 22 patients (44.83%) and scale Ⅳ (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P<0.05), and no differences in response were found among different primary sites (P>0.05). Our study indicates that topical application of 3% propranolol hydrochloride gel is effective and safe in treating IHs.

Clinical observations on the treatment of infantile hemangiomas with topical imiquimod 5% cream

Objective： To observe the efficacy and safety of topical imiquimod 5% cream in the treatment of uncomplicated infantile hemangiomas （IHs）. Methods： A total of 68 IHs were treated with topical imiquimod 5% cream. Among them, 36 were superficial, 22 were mixed, and 10 were deep. The size of IHs ranged from 1.0 cm × 1.5 cm to an area of a whole forearm. All the hemangiomas were in a proliferative stage. Imiquimod was applied 3 times weekly in 44 patients and 5 times weekly in 24 patients for up to 36 weeks. Results： All superficial IHs improved, and 18 achieved complete clinical resolution, 10 had excellent improvement, 5 showed moderate improvements, and 3 patients displayed minimal improvement. Two mixed IHs showed excellent improvement, 3 showed moderate improvement and 5 manifested minimal improvements. The remaining 12 mixed IHs and all deep IHs did not respond to the therapy. The total incidence of local adverse events was 58.82%（40/68）, which included erythema or edema, local itching, incrustation or peeling, erosion or ulceration, although most of these were mild to moderate reactions and did not affect the treatment. Scarring occurred in 2 mixed IHs. No systemic side effects developed. Conclusion： Imiquimod 5% cream may be a safe and effective alternative for the treatment of superficial IHs and some mixed IHs in which the superficial component predominates. An appropriate treatment duration for proliferative IHs treated with this therapy may be 24 weeks. Some local adverse events, such as crusting and erosion with possible scarfing potential may occur and should be addressed by prompt, but temporary, discontinuation of the imiquimod. Topical imiquimod 5% cream can be prudently used in the treatment of IHs larger than 5.0 cm × 5.0 cm in newborns and infants less than 6 months of age. To our knowledge, this is the largest IH group treated with imiquimod that has been reported in the literature to date.

Analysis of the therapeutic evolution in the management of airway infantile hemangioma

AIM: To analyze the evolution in the management of airway infantile hemangioma(AIH) and to report the results from 3 pediatric tertiary care institutions.METHODS: A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed. RESULTS: Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo(range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases(no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients(in 5 of them as a single treatment) with a response rateof 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients(in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo(range, 5-10); complications were not observed. CONCLUSION: Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH.

Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review

BACKGROUND We have previously proved that treatment of thick/deep infantile hemangiomas (IHs) with a long-pulse Alexandrite laser was clinically effective and safe. This article aims to investigate the efficiency of long-pulse Alexandrite laser use in treating thick and high-risk IHs located in particular anatomic areas and provides some new data on this issue. CASE SUMMARY A two-month-old girl with a thick and high-risk IH covering most of the right labia majora was examined in this study. The infant received four treatment sessions at 4- to 6-wk intervals with a long-pulse Alexandrite laser with settings as follows: 3 ms pulse duration, 8 mm spot size, 45 to 50 J/cm2 fluences, and dynamic cooling device (DCD) spray duration of 90 ms with a delay of 80 ms. Following each of the four treatment sessions, the IH showed a remarkable reduction in thickness and size without any sign of relapse. Ten months after the last treatment, the IH had completely regressed without adverse effects. During the laser treatment, no severe side effects were observed;blistering occurred only immediately after treatment and then scabbed over the next day, gradually improving in the following days. CONCLUSION Long-pulse Alexandrite laser treatment may be considered one of the first-line noninvasive therapeutic options for the treatment of thick IH.

Clinical Evaluation of Color Doppler Ultrasound in Selecting the Optimal Treatment Modality for Infantile Hemangioma

Objective We investigated the efficacy and safety of 1064 nm Nd： YAG laser, intense pulsed light （IPL）, and lauromacrogol injection in the treatment of hemangioma, in order to evaluate the value of color Doppler ultrasound guidance in choosing the optimal treatment modality. Methods Infantile patients who were clinical diagnosed as hemangiomas were randomly divided into group A, who had color Doppler ultrasound examinations before the treatment, and group B who had the treatment without ultrasound evaluation. Patients in the group A were assigned into subgroups according to the depth of lesion by sonography： group A-1 for those who had a lesion depth 〈1.2 mm, and took intense pulsed light therapy; group A-2 for those who had a lesion depth ≥1.2mm and 〈 3 mm, and took long pulse 1064 nm Nd：YAG laser therapy; group A-3 for those who had a lesion depth ≥3mm and 〈5 mm, and were treated by IPL combined with long pulse 1064 nm Nd：YAG laser treatment; Group A-4 for those who had a lesion depth ≥5 mm, and took lauromacrogol injection therapy. Patients in the group B took long pulse 1064 nm Nd：YAG laser treatment without preoperative ultrasound evaluation. The efficacy and adverse reactions of the treatments between the groups were evaluated and compared statistically. Results Totally 113 patients with 128 skin lesions were enrolled in this study, 85 in the group A （mean age 6.8±7.9 months） and 28 in the group B （mean age 6.9±9.9 months）. The mean depth of hemangioma was 3.3±1.1 mm in the group A, ranging from 0.5-7.8 mm, with 0.8±0.4 mm, 2.2±0.4 mm, 4.2±0.6 mm and 6.2±0.7 mm in group A1, A2, A3 and A4, respectively. The cure rates and effective rates in the group A were significantly higher than those in the group B （cure rates： 64.5% vs 56.3%, U=3.378, P=0.045; effective rates： 89.5% vs 78.1%, U=4.163, P=0.041）. The adverse effect rates of the group A （vesicle 20.0%, pigmentation 46.9%, scarring 17.7%） were lower than those of the group B （vesicle 21.9%, pigmentation 60.4%, scarring 25.0%）. Incidences of pigmentation and scarring were statistically significantly different （U=3.884, P=0.034, and U=4.016, P=0.032 respectively） between the two groups. Conclusion With the guidance of color Doppler ultrasound, the efficacy and safety of long pulse 1064 nmNd：YAG laser, intense pulsed light, and lauromacrogol injection in the treatment of infantile hemangioma have better outcomes compared to laser treatment alone without preoperative ultrasound examination.

Response to magnesium sulfate and adrenocorticotropic hormone combination therapy for infantile spasms with failed first-line treatments

Importance:Infantile spasm(IS)is a kind of refractory epilepsy.The first-line treatments for IS are adrenocorticotropic hormone(ACTH),oral corticosteroids,and vigabatrin.Objective:This study aimed to evaluate the efficacy of magnesium sulfate and ACTH(MgSO_(4)+ACTH)combination therapy in patients with IS who failed first-line treatments.Methods:In this retrospective study,the clinical data of patients with IS who failed first-line treatments were collected in the Chinese PLA General Hospital.Patients received MgSO_(4)+ACTH combination therapy after first-line treatments failed.The course of treatments was 2 weeks.The therapeutic dose of ACTH and MgSO_(4)was 2.5 U·kg^(-1)·d^(-1)and 0.25 g·kg^(-1)·d^(-1),respectively.Results:A total of 229 patients with IS who failed the first-line treatments were collected.At the end of the MgSO_(4)+ACTH combination treatment,the seizure-free rate was 48.5%(111/229),and the resolution of hypsarrhythmia on electroencephalogram(EEG)was 72.1%(165/229).About 21.4%(49/229)of patients showed side effects,including infectious diseases,hypokalemia,and diarrhea.Interpretation:For patients with IS who failed first-line treatments,in terms of the seizure-free rate and resolution of hypsarrhythmia on EEG,MgSO_(4)+ACTH combination therapy can be considered.

Effect of Topical Propranolol Gel on Plasma Renin,Angiotensin Ⅱ and Vascular Endothelial Growth Factor in Superficial Infantile Hemangiomas

The effect of topical propranolol gel on the levels of plasma renin,angiotensin Ⅱ（ATⅡ） and vascular endothelial growth factor（VEGF） in superficial infantile hemangiomas（IHs） was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment,1 and 3 months after application of topical propranolol gel for the levels of plasma renin,AT Ⅱand VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st,and 3rd month after application was 45%,and 82% respectively. The levels of plasma renin,AT and VEGF in patients preⅡ-treatment were higher than those in healthy infants（565.86±49.66 vs. 18.19±3.56,3.20±0.39 vs 0.30±0.03,and 362.16±27.29 vs. 85.63±8.14,P〈0.05）. The concentrations of VEGF and renin at 1st and 3rd month after treatment were decreased obviously as compared with those pre-treatment（271.51±18.59 vs. 362.16±27.29,and 405.18±42.52 vs. 565.86±49.66 P〈0.05; 240.80±19.89 vs. 362.16±27.29,and 325.90±35.78 vs. 565.86±49.66,P〈0.05,respectively）,but the levels of plasma AT declined slightly Ⅱ（2.96±0.37 vs. 3.20±0.39,and 2.47±0.27 vs. 3.20±0.39,P〉0.05）. It was indicated that the increased renin,AT Ⅱand VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.

The apoptosis in various stages of infantile hemangioma

Objective: To detect the apoptosis in various stages of infantile hemangioma. Methods:Total 52 samples of infantile hemangioma (including 8 fresh samples) were included in this study. Agarose gel electrophoresis, transmission electron microscopy(TEM) and in situ TdT mediated dUTP-biotin nick end labeling(TUNEL) staining were used to observe the apoptosis. H-E staining was used to analyze the number of cells,the number and area of microvessels in hemangiomas. Results: The typical “ladder” occurred in the DNA electrophoresis of the hemangioma tissue in the late proferating stage. Many apoptotic cells were found in infantile hemangiomas with TEM. TUNEL staining identified that there were apoptotic cells througout the pathologic evolution of infantile hemangioma and the AI(%) was the highest in the late proferating stage. There existed close relationship between the AI(%) and the total number of cells in hemangioma. Conclusion: The decrease of cells resulted from the apoptosis may be the major cause of the spontaneous involution of infantile hemangioma.

Dermoscopic Appearances in the Superficial and Deep Type of Infantile Hemangioma

Infantile hemangioma is clinically classified as superficial, superficial and deep (mixed), and deep. Dermoscopy can be used for analyzing vascular structure and for classifying infantile hemangioma. Here, we focus on vascular features of the superficial and deep type of infantile hemangioma and show the three characteristic dermoscopic forms, mostly reddish, diffuse reddish, and cerebriform reddish.