Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

Aesthetic outcome of intralesional injection of lauromacrogol as a single-agent treatment for uncomplicated infantile hemangiomas: A long-term follow-up study.

Infantile hemangiomas (IH) are at risk of incomplete regression with remnant permanent sequelae, ranging from passive waiting for spontaneous regression to active systemic administration. The application of traditional therapy involving injection of a sclerosing agent is limited due to the difficulty in achieving cosmetic improvement. This study aimed to explore a new injection method that could not only promote tumor regression but also achieve cosmetic improvement. A total of 122 IH (from 109 children) injected intralesionally with lauromacrogol in the Plastic Surgery Department of Fujian Medical University Union Hospital between 1 January 2012 and 1 June 2019 were enrolled in this study. The mean follow-up time was 2.9 years. Of 122 lesions studied, 111 (91.0%) achieved complete regression, 10 (8.2%) achieved significant regression and one (0.8%) achieved moderate regression. In terms of aesthetic appearance, 70 (57.4%) IH had no sequelae and the A score was 5/5. Twenty-one (17.2%) IH had minimal hyperpigmentation, hypopigmentation or telangiectasia and the A score was 4/5. Thirty-one (25.4%) IH had left mild or relatively obvious sequelae and the A score was 1-3/5. None of the 122 IH involved had rebound growth after terminating the treatment. Hyper- or hypopigmentation gradually faded over time and part of the IH had already returned to normal appearance by the time of long-term follow up. The results indicated that this new type of injection therapy significantly promoted the regression of uncomplicated IH and helped achieve the expected cosmetic appearance.

Removal of dissolved sulfides in aqueous solution by activated sludge: mechanism and characteristics.

Activated sludge recycling has been developed as a novel technique to directly prevent volatile sulfides emission from wastewater influents. In this study, mechanisms and characteristics of dissolved sulfides removal in aqueous solution by activated sludge were investigated. When DO content in water was 0.49mg/L, 70% of removed dissolved sulfides were released back from the activated sludge by lowering pH to 1. The SEM/EDS result revealed that removed sulfur was fixed in activated sludge and the XPS result showed that fixed sulfur had an oxidation state of -2. FTIR results showed that primary amine group (R-NH2) could be one of the radical groups bonding sulfides. All these results verified that sulfides removal by activated sludge is primarily attributed to adsorption, rather than biodegradation, under low DO conditions in 40min. The equilibrium isotherm data fit the Langmuir isotherm model well. The maximum adsorption capacity (q0) ranged in 25-38mg/g at temperatures of 10-40°C. The adsorption kinetic data fit the pseudo-second-order model well. The amounts of adsorbed sulfides at equilibrium (qe) were positively proportional to temperature, initial sulfides concentration and agitation speed. These results indicate that sulfides adsorption could be a chemical sorption or ion exchange process.

[Chinese expert consensus on the use of topical timolol maleate treatment of infantile hemangiomas].

Non-selective ß-blocker propranolol has been proved by FDA as the first-line agent for infantile hemangioma (IH) with dramatic response. To reduce the side effects caused by systemic administration of propranolol, timolol maleate treatment has been increasingly used as an alternative to systemic ß-blockers and watchful waiting for many IH patients in recent years. However, the appropriate indications, drug dosage, dosing regimen, time for initiation, optimal duration, monitoring for side effects still remains controversial. To standardize the use of topical timolol in treating IH, avoid overtreatment or under-treatment, as well as minimize complications, a Chinese expert consensus on the use of topical timolol treatment of IH has been approved and written by a multidisciplinary experts group based on an up-to-date literature review and repeated discussion, which can be used to reduce inappropriate variations in clinical practice and to promote the delivery of high quality, evidence-based health care for IH patients.

[Transposition of orbital fat and orbicularis muscle flap over the orbital rim for correction of lower eyelid pouches complicated with lacrimal groove deformity].

OBJECTIVE: To introduce the experience in the treatment of lower eyelid pouches orbital rim. METHODS: An incision was made along the margin of lower eyelid and dissection was performed under the orbicularis muscle to expose the orbital septum and periosteum of lower orbital rim. The fat released from orbital septum was transposed just below the lower orbital rim and fixed on the periosteum. If lacrimal groove deformity was not corrected completely, the musculocutaneous flap, which may be excised beside the incision, was kept to correct the deformities further with only the muscle portion. RESULTS: 72 cases with lower eyelid pouches complicated with lacrimal groove deformities were treated with transposition of orbital fat and orbicularis muscular flaps. Satisfactory results were achieved in all the patients after a follow-up period of 3-6 months. CONCLUSION: It is an effective and feasible technique to correct lacrimal groove deformities with transposition of orbital fat and orbicularis muscular flaps.

[A prospective study of propranolol as first-line treatment for problematic infantile hemangioma in China].

OBJECTIVE: To prospectively assess the efficacy and safety or propranolol as a first-line treatment for problematic infantile haemangioma in China. METHODS: From Mar. 2009 to Feb. 2010, 78 patients with problematic infantile hemangioma were included in the prospective study. The characteristics of the tumor, including sex, age, site, complications, were recorded. The response to treatment at 1 week, at 1 month and at the end of treatment was evaluated. The efficacy of treatment was graded as no response, stabilization, or accelerated regression. The indications for treatment, side effects and relapse after treatment were documented. The mean follow-up period was 16.7 months (range, 12.1-23.6 months). RESULTS: Oral therapy was initiated at mean age of 3.7 months (range, 1.1-9.2 months) as first-line therapy. The mean age at the end of treatment was 11.2 months (range, 5.2-22.3 months). The treatment was lasted for 7.6 months (range, 2. 1-18.3 months). One week after treatment beginning, the hemangioma growth was controlled in all the patients. The accelerated regression was achieved in 88.5% (69/78) of patients after one week of treatment, and 98.7% (77/78) of patients after 1 month of treatment and at the end of treatment. Ulceration was occurred in 14 cases before treatment, which was healed after treatment for 2 months. Minor side effects were happened in 15.4% (12/78) of patients. Rebound growth of lesion was noticed in 35.9% (28/78) of patients. CONCLUSIONS: Propranolol is effective in the treatment of infantile hemangioma with minor side effect. We suggest it should be used as the first-line treatment.

[Clinical application of imiquimod for the treatment of infantile hemangiomas].

OBJECTIVE: To explore the clinical application of imiquimod for the treatment of infantile hemangiomas (IH). METHODS: 320 children with IH, including 250 superficial cases, 20 deep cases, and 50 mixed cases, were treated with 5% imiquimod cream every other day for 16 weeks. The clinical efficacy and side effects were evaluated at one year of age. RESULTS: The total effective rates of the superficial, deep, and mixed IH were 61.2% (153/250), 10.0% (2/20) and 60.0% (30/50) respectively, showing no statistical difference between superficial and deep type (P = 0.874), but significant difference between superficial and mixed (P < 0.01), deep and mixed type (P < 0.01). 56.0% (28/50) of mixed IH showed proliferation of its deep lesions. Slight skin erythema and crusting were the most common side effects. CONCLUSIONS: 5% imiquimod cream is effective and safe in superficial IH and superficial lesions of mixed IH with minimal skin reactions. The dysplasia of local tissue and systemic growth retardation are not found. It should be avoided to apply the cream to IH located around the cavities and skin fold. Imiquimod cream is a simple and convenient home-nursing medication. It can reduce care burden of family. Thus topical use of imiquimod can be considered as a good clinical indication for the treatment of superficial lesions of IH.

[Estrogen on stimulating the angiogenesis of children's hemangioma in vitro].

OBJECTIVE: To demonstrate that estrogen stimulates the angiogenesis of children' s hemangioma. METHODS: A piece of hemangioma biopsy was embedded in fibrin gel, and a model in vitro of angiogenesis of human hemangioma was then established. The angiogenesis of hemangioma in each group was interfered by the estrogen and tamoxifen. There were four groups divided into the followings: the group with estrogen, the group with tamoxifen, the group with estrogen + tamoxifen and the control. The dimension of newborn tubule area in the 3rd, 6th, 9th day after the culture was calculated to compare statistically differences among the groups. RESULTS: In the model of angiogenesis of hemangioma, microvessels grew out from the tissue sample in 2 to 3 days after the culture, and in 8 to 9 days a complex network of microvessels had been shown, the tending to inactivity. On the 3rd,6th and 9th day after the culture the dimension of newborn tubule area of the group of estrogen [(2.84 +/- 0.20) mm2 (12.93 +/- 0.85) mm2 (22.47 +/- 1.40) mm2] were larger than those of the control [(1.98 +/- 0.17) mm2, (7.51 +/- 0.48) mm2, (11.26 +/- 0.73) mm2]. Those of the group of estrogen + tamoxifen [(1.08 +/- 0.11) mm2, (3.54 +/- 0.31) mm2, (5.72 +/- 0.40 mm2] and the group of tamoxifen [(1.13 +/- 0.14) mm2 (4.26 +/- 0.29) mm2, (6.08 +/- 0.42) mm2] were smaller than those of the groups of the estrogen and the control (P < 0.05). CONCLUSIONS: The estrogen may stimulate the angiogenesis of children's hemangioma, and the tamoxifen may reverse the process.

[A three-dimension in vitro model for angiogenesis of hemangioma].

OBJECTIVE: To create a three dimension (3D) in vitro model for angiogenesis of hemangioma. METHOD: The fragment of hemangioma specimen was embedded in fibrin gel to set up the three-dimension (3D) in vitro model for angiogenesis of hemangioma. RESULT: In the model, microvessels grew out from the tissue fragments at the 2nd to 3rd day after culture, and at the 8th to 9th day a compact network of microvessels come into being, then tending to be stationary. The compact network around the tissue fragment was confirmed to be blood vessels by immunohistochemistry and electron microscopy. CONCLUSION: This model helps to study the mechanism of hemangioma angiogenesis and investigate the drugs of anti-angiogenesis.