Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer.

BACKGROUND: ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition (EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction (qPCR) and Western blotting. RESULTS: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. CONCLUSIONS: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.

A Clinical Observation Study for Transnasal Endoscopic Marsupialization in the Treatment of Maxillary Cyst.

The aim of this study was to investigate the feasibility and evaluate the clinical effects of transnasal marsupialization of maxillary cyst under nasal endoscope. Twenty patients with maxillary bone cysts were treated with endoscopic marsupialization. According to the location of the maxillary bone cyst, the opening window was selected in the nasal base or the inferior or middle nasal meatus. The cyst wall of the window was removed, and the fluid was drained out. The diameter of the opening window was more than 1 cm, so that the cyst and the maxillary sinus can be fused into a cavity. This ensured nasal drainage through the cyst cavity and nasal cavity or maxillary sinus. The patients were followed up for 6 to 18 months. No serious complications occurred. The cyst wall epithelialized 2 or 3 months after the operation, and the cyst cavity drained well with no recurrence. Intranasal marsupialization under a nasal endoscope is a feasible alternative for the treatment of maxillary cysts. It makes the procedure simple, safe, less traumatic, has definite clinical effects, and low recurrence rate. Especially suitable for maxillary cysts protruding into the nasal floor or maxillary sinus.

HOXA10 promote pancreatic cancer progression via directly activating canonical NF-κB signaling pathway.

BACKGROUND: Although transcription factor homeobox A10 (HOXA10) plays an important role in regulating the development of the pancreas, a pathway of HOXA10 participates in pancreatic ductal adenocarcinoma (PDAC) progression has not been revealed. METHODS: Immunohistochemistry assays were applied to demonstrate the relationship between HOXA10 expression and PDAC progression. Functional assays were used to illustrate the oncogenic role of HOXA10 in PDAC progression. Regulatory mechanisms of HOXA10 induced IKKß gene transcription and the nuclear transcription factor kappa B (NF-κB) signal pathways activation were also investigated in PDAC cells. RESULTS: In the current study, we show that HOXA10 expression increased in PDAC with higher tumor stage and poor patient survival in public RNA-seq data suggesting HOXA10 is associated with PDAC progression. HOXA10 promotes PDAC cell proliferation, anchorage colony formation, and xenograft growth by activating canonical NF-κB signaling both in vitro and in vivo. Mechanically, HOXA10 up-regulates IKKß gene transcription directly and subsequently sustain the activation of NF-κB independent of tumor necrosis factor-alpha in PDAC cells. CONCLUSION: Collectively, up-regulation of HOXA10 gene expression promote cell growth and tumor progression through directly activating canonical NF-κB signaling in PDAC.

Glycolysis addiction compensating for a defective pentose phosphate pathway confers gemcitabine sensitivity in SETD2-deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by genetic mutations and/or epigenetic dysregulation. Gemcitabine chemotherapy is the first-line regimen for pancreatic cancer but has limited efficacy. Our previous study revealed the role of SETD2-H3K36me3 loss in the initiation and metastasis of PDAC, but little is known about its role in tumor metabolism. Here, we found that SETD2-deficient PDAC enhanced glycolysis addiction via upregulation of glucose transporter 1 (GLUT1) to meet its large demand for glucose in progression. Moreover, SETD2 deficiency impaired nucleoside synthesis by directly downregulating the transcriptional level of transketolase (TKT) in the pentose phosphate pathway. The metabolic changes confer SETD2-deficient PDAC cells with increased sensitivity to gemcitabine under glycolysis restriction conditions. Collectively, our study provides mechanistic insights into how SETD2 deficiency reprograms glycolytic metabolism to compensate for insufficient nucleoside synthesis, suggesting that glycolysis restriction combined with gemcitabine might be a potential therapeutic strategy for PDAC patients with SETD2 deficiency.

Biodegradation of Terrigenous Organic Matter in a Stratified Large-Volume Water Column: Implications of the Removal of Terrigenous Organic Matter in the Coastal Ocean.

Large amounts of terrigenous organic matter (TOM) are delivered to the ocean every year. However, removal processes of TOM in the ocean are still poorly constrained. Here, we report results from a 339-day dark incubation experiment with a unique system holding a vertically stratified freshwater-seawater column. The quality and quantity of dissolved organic matter (DOM), RNA-based size-fraction microbial communities, and environmental factors were high-frequency-monitored. Microbial processes impacted TOM composition, including an increased DOM photobleaching rate with incubation time. The mixed layer had changed the bacterial community structure, diversity, and higher oxygen consumption rate. A two-end member modeling analysis suggested that estimated nutrient concentrations and prokaryotic abundance were lower, and total dissolved organic carbon was higher than that of the measured values. These results imply that DOM biodegradation was stimulated during freshwater-seawater mixing. In the bottom layer, fluorescent DOM components increased with the incubation time and were significantly positively related to highly unsaturated, oxygenated, and presumably aromatic compound molecular formulas. These results suggest that surfaced-derived TOM sinking leads to increased DOM transformation and likely results in carbon storage in the bottom water. Overall, these results suggest that microbial transforming TOM plays more important biogeochemical roles in estuaries and coastal oceans than what we know before.

Spatial dynamics of active microeukaryotes along a latitudinal gradient: Diversity, assembly process, and co-occurrence relationships.

Recent global warming is profoundly and increasingly influencing the Arctic ecosystem. Understanding how microeukaryote communities respond to changes in the Arctic Ocean is crucial for understanding their roles in the biogeochemical cycles of nutrients and elements. Between July 22 and August 19, 2016, during cruise ARA07, seawater samples were collected along a latitudinal transect extending from the East Sea of Korea to the central Arctic Ocean. Environmental RNA was extracted and the V4 hypervariable regions of the reverse transcribed SSU rRNA were amplified. The sequences generated by high throughput sequencing were clustered into zero-radius OTUs (ZOTUs), and the taxonomic identities of each ZOTU were assigned using SINTAX against the PR2 database. Thus, the diversity, community composition, and co-occurrence networks of size fractionated microeukaryotes were revealed. The present study found: 1) the alpha diversity of pico- and nano-sized microeukaryotes showed a latitudinal diversity gradient; 2) three distinct communities were identified, i.e., the Leg-A, Leg-B surface, and Leg-B subsurface chlorophyll a maximum (SCM) groups; 3) distinct network structure and composition were found in the three groups; and 4) water temperature was identified as the primary factor driving both the alpha and beta diversities of microeukaryotes. This study conducted a comprehensive and systematic survey of active microeukaryotes along a latitudinal gradient, elucidated the diversity, community composition, co-occurrence relationships, and community assembly processes among major microeukaryote assemblages, and will help shed more light on our understanding of the responses of microeukaryote communities to the changing Arctic Ocean.

Top-down controls on nutrient cycling and population dynamics in a model estuarine photoautotroph-heterotroph co-culture system.

Viral lysis and protistan grazing are thought to be the major processes leading to microbial mortality in aquatic environments and thus regulate community diversity and biogeochemical cycling characteristics. Here, we studied nutrient cycling and bacterial responses to cyanophage-mediated photoautotroph lysis and ciliate predation in a model Synechococcus-heterotroph co-culture system. Both viral lysis and Euplotes grazing facilitated the transformation of organic carbon from biomass to dissolved organic matter with convention efficiencies of 20%-26%. The accumulation of ammonium after the addition of phages and ciliates suggested the importance of recycled NH4+ occurred in the interactions between Synechococcus growth and heterotrophic bacterial metabolism of photosynthate. The slower efficiency of P mineralization compared to N (primarily ammonium) indicated that P-containing organic matter was primarily integrated into bacterial biomass rather than being remineralized into inorganic phosphate under C-rich conditions. In the cyanophage addition treatment, both Fluviicola and Alteromonas exhibited rapid positive responses to Synechococcus lysing, while Marivita exhibited an apparent negative response. Further, the addition of Euplotes altered the incubation system from a Synechococcus-driven phycosphere to a ciliate-remodelled zoosphere that primarily constituted grazing-resistant bacteria and Euplotes symbionts. Top-down controls increased co-culture system diversity and resulted in a preference for free-living lifestyles of dominant populations, which was accompanied by the transfer of matter and energy. Our results indicate top-down control was particularly important for organic matter redistribution and inorganic nutrient regeneration between photoautotrophs and heterotrophs, and altered bacterial lifestyles. This study consequently sheds light on marine biogeochemical cycling and the interaction networks within these dynamic ecosystems.

The Calcium Phosphate Modified Titanium Implant Combined With Platelet-Rich Plasma Treatment Promotes Implant Stabilization in an Osteoporotic Model.

ABSTRACT: Osteoporosis as a kind of systemic bone metabolic disease has become one of the most prevalent diseases among the middle- and old-age, characterized with low bone mass and disruptive osseous microenvironment. The poor bone condition both in quantity and quality makes it daunting for osteoporotic patients who are submitted to dental implantation, joint replacement therapy, or orthopedic surgery. Since calcium phosphate (CaP) and platelet-rich plasma (PRP) treatment, all have improving the effect on bone regeneration. Inspired by this fact, the authors introduced a kind of novel implant with CaP modified surface by HPT (hydrothermal & pressure) treatment in this study. After producing, the authors tested its physicochemical properties through scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscope (XPS) and contact-angle measurement. Then the authors desired to investigate the effect of this CaP-modified implant on bone regeneration and stabilization maintenance combined with PRP treatment by establishing an osteoporotic rat model. After 3 months of surgery, the authors collected all the specimens and evaluated new bone formation by micro-computed tomography (micro-CT) analysis, biomechanical test, and histologic assessment. All the results in vivo experiment showed the CaP modified implant combined with PRP treatment could improve the osteoinductive effect under osteoporotic condition, leading to better maintenance for stabilization between bone and implant interface, which might be rendered as a promising clinical method for osteoporotic patients when they receive orthopedic surgeries.

Comparative Study on the Treatment of Ankyloglossia by Using Er:YAG Laser or Traditional Scalpel.

ABSTRACT: The aim of this study was to compare, respectively, postoperative pain, wound healing, and patient satisfaction following lingual frenum extension treated with the Erbium Yttrium aluminum garnet. (Er:YAG) laser or the conventional scalpel. Twenty-eight patients receiving lingual frenectomy were randomly assigned to the Er:YAG laser group (n = 15) or the traditional scalpel group (n = 13). The surgical parameters were set to 3W or 4W basing on types of the lingual frenum when the Er:YAG laser was working. The same procedure was applied to the traditional scalpel group with transverse incision and longitudinal suture. The postoperative pain, wound healing and patient satisfaction were evaluated at 3 hours, 3, 7, and 30 days after operation. The visual analog scale score of postoperative pain in Er:YAG laser group was lower than that in traditional scalpel group at each time point. The wound healing score of the laser group were significantly lower than that of the traditional scalpel group at 3 and 7 days after surgery. There was no significant difference in mental, diet, and language satisfaction between the 2 groups at different time points after operation. In conclusion, Er:YAG laser was superior to the scalpel regarding minor soft-tissue surgery, and it could relieve the pain and discomfort of patients in the early stage of wound.

Phylogeny and Genetic/Morphological Variation of Strombidinopsis minima-like Species (Ciliophora: Choreotrichia).

Six isolates of mineral-enveloped Strombidinopsis minima-like species were collected from the coastal waters across several regions in Korea. Morphological observations and molecular analyses were performed. The ribosomal DNA sequences (including small subunit ribosomal DNA, internal transcriber spacer 1-5.8S ribosomal DNA-internal transcriber spacer 2; and part of large subunit ribosomal DNA) of these six isolates were compared. Their morphological characteristics were also compared with those of S. minima populations reported. The marked genetic differences (with a similarity range of 96.85-98.48%) in SSU rDNA among these S. minima-like entities suggest the existence of multiple species. This finding is also supported by morphological variations detected in this study and reported in the literature (e.g. 15-32 collar membranelles in different populations). In addition, S. minima-like species are clustered with S. batos and S. sinicum, and therefore, our SSU rDNA results support previous results suggesting that the genus Strombidinopsis is not monophyletic in origin. Further collection of morphological and molecular data may facilitate the determination of a new genus carrying mineral-enveloped Strombidinopsis species.

Nonmineralized and Mineralized Silk Fibroin/Gelatin Hybrid Scaffolds: Chacterization and Cytocompatibility In Vitro for Bone-Tissue Engineering.

In this study, nonmineralized silk fibroin/gelatin (SF/G) hybrid scaffolds and the mineralized SF/G/hydroxyapatite (SF/G/HA) hybrid scaffolds were fabricated using vacuum freeze-drying method and biomineralization technique. The morphology and mechanical properties of the 2 hybrid scaffolds were characterized. Furthermore, the cytotoxic profiles of the hybrid scaffolds were investigated in vitro by seeding the human osteoblast cells (hFOB1.19). The 2 hybrid scaffolds were both highly porous and the pore sizes of the SF/G as well as SF/G/HA hybrid scaffolds were 260 ±â€Š58 µm and 210 ±â€Š35 µm, respectively. Compared with the SF/G hybrid scaffold, the SF/G/HA hybrid scaffolds exhibited significantly enhanced compressive strength and modulus. Significant early cell adhesion and proliferation on the SF/G hybrid scaffolds were observed, while SF/G/HA hybrid scaffolds effectively improved osteogenic differentiation of hFOB1.19 after 10 days of coculture. The results confirmed that the 2 hybrid scaffolds were both cytocompatible and had almost no negative effects on the hFOB1.19 in vitro. However, the SF/G/HA hybrid scaffolds tended to be more promising for application in bone-tissue engineering with good mechanical property and osteogenic differentiation.

Pigmented microbial eukaryotes fuel the deep sea carbon pool in the tropical Western Pacific Ocean.

Phototrophic microbial eukaryotes dominate primary production over large oceanic regions. Due to their small sizes and slow sinking rates, it is assumed they contribute relatively little to the downward export of organic carbon via the biological pump. Therefore, the community structure of phototrophic cells in the deep ocean has long been overlooked and remains largely unknown. In this study, we used an integrative approach, including epifluorescence microscopy, sequencing of 18S rRNA and photosystem-II psbA gene transcripts, to investigate phototrophic microbial eukaryotes in samples collected from the tropical Western Pacific Ocean. It was found that: (i) pigmented nano-sized eukaryotes (PNEs) are ubiquitous in the deep Western Pacific Ocean down to 5000 m depth; (ii) the PNE community is dominated by cells 2-5 µm in size; (iii) their abundance is significant, averaging 4 ± 1 (± s.e.) cells ml-1 in waters below 1000 m which is comparable to that of heterotrophic nanoflagellates; (iv) the active pigmented microbial eukaryotes in the deep waters are highly diverse and dominated by Haptophyta followed by Chlorophyta and Bacillariophyta; (v) PNEs in deep waters were likely transported from surface ocean by various fast-sinking mechanisms, thus contributing to the biological pump and fuelling the deep-sea communities by supplying fresh organic carbon.

Comparative study on the incision healing of the palatal mucosa by using Er:YAG laser or traditional scalpel in the SD rats.

The aim of this study was to compare the histology of wound healing following incisions with the scalpel or the Er:YAG laser in the palatal mucosa of SD rats. Two types of wounds were performed with the stainless steel scalpel or the Er:YAG laser in the palatal mucosa of SD rats, while the adjacent untreated palatal mucosa was chosen as control. Rats were sacrificed on day 1, day 3, day 7, and day 30 post-surgery. Biopsy samples from each wound were examined and the expression of IL-1ß and TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA). The early postoperative incision of the scalpel group had obvious bleeding and swelling, while the laser wound mainly covered the surface of white pseudomembrane. The infiltration of neutrophils and lymphocytes in the stroma of the scalpel incision was more than that of the laser group. Compared to the laser group, 1 and 3 days after operation, the TGF-ß1 content of the scalpel group were significantly increased (P = 0.032 and 0.019). Seven days after operation, the TGF-ß1 content of two groups was decreased. TGF-ß1 expression of control group was obviously increased (P > 0.05); 1, 3, and 7 days after operation, the traditional scalpel amount of IL-1ß expression was significantly higher than that of control group (P = 0.000, 0.000, and 0.001). Postoperative day 1, IL-1ß expression of laser group and control group had no significant difference (P = 0.572). Three days after operation, IL-1ß expression of laser incision was increased and was significantly higher than that in control group (P = 0.032), however lower than the scalpel group (P = 0.03). Seven days after operation, the IL-1ß expression of two groups had no significant difference (P = 0.333); however, the IL-1ß expression of two groups were significantly higher than that of the control group (P = 0.02 and 0.001). Compared to the traditional scalpel, the incision of Er:YAG laser has smaller inflammation reaction, more pseudomembrane coverage, and minimal damage of the mucoperiosteal tissue.

A Study on Environmental Factors for Nonsyndromic Cleft Lip and/or Palate.

The aim of the study was to investigate the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCL/P) in Yantai District, China. A retrospective case-control study was carried out. A total of 236 NSCL/P children were selected from Department of Oral and Maxillofacial Surgery of Yantai Stomatological Hospital between September 2013 and December 2016 as cases; 209 controls were chosen from other diagnosis in the same department during the same period. The 2 groups matched age and sex. The parents of participants were inquired regarding the risk factors, and the answers were filled in a questionnaire by physicians. Chi-square and multivariate logistic regression analysis were used to analysis the data. There was significantly increased NSCL/P risk with high maternal age (P =0.002), family history (P = 0.001), abortion history (P = 0.033), poor parental education level (P = 0.008), maternal smoking (P = 0.044), maternal alcohol (P = 0.039), common cold or fever (P = 0.035), drug use (P = 0.006), and maternal stress (P = 0.049). Reduced NSCL/P risk was found with folic acid supplementation (P = 0.005), adequate maternal age (P = 0.002), and high parental education (P = 0.001). The proper amount of folic acid, the appropriate age of childbearing, and the high education were the protective factors of NSCL/P, whereas family history, abortion history, drug use during pregnancy, maternal tobacco and alcohol, and maternal stress were the risk factors for NSCL/P in Yantai District, China.

Distribution and Diversity of Microbial Eukaryotes in Bathypelagic Waters of the South China Sea.

Little is known about the biodiversity of microbial eukaryotes in the South China Sea, especially in waters at bathyal depths. Here, we employed SSU rDNA gene sequencing to reveal the diversity and community structure across depth and distance gradients in the South China Sea. Vertically, the highest alpha diversity was found at 75-m depth. The communities of microbial eukaryotes were clustered into shallow-, middle-, and deep-water groups according to the depth from which they were collected, indicating a depth-related diversity and distribution pattern. Rhizaria sequences dominated the microeukaryote community and occurred in all samples except those from less than 50-m deep, being most abundant near the sea floor where they contributed ca. 64-97% and 40-74% of the total sequences and OTUs recovered, respectively. A large portion of rhizarian OTUs has neither a nearest named neighbor nor a nearest neighbor in the GenBank database which indicated the presence of new phylotypes in the South China Sea. Given their overwhelming abundance and richness, further phylogenetic analysis of rhizarians were performed and three new genetic clusters were revealed containing sequences retrieved from the deep waters of the South China Sea. Our results shed light on the diversity and community structure of microbial eukaryotes in this not yet fully explored area.

Multi-gene-based phylogenetic analysis of oligotrich ciliates with emphasis on two dominant groups: Cyrtostrombidiids and strombidiids (Protozoa, Ciliophora).

Phylogenetic analyses of ciliated protists are frequently based on single molecular markers, usually the small subunit ribosomal RNA gene (SSU rDNA), despite the well-known limitations of this approach. Here, 78 new sequences of three linked genes (SSU rDNA, ITS1-5.8S rDNA-ITS2, LSU rDNA) were characterized and applied to phylogenetic analyses of oligotrichs (s. str.). It was found that: (1) three taxa, that is tontoniids, pelagostrombidiids and cyrtostrombidiids should be split from the family Strombidiidae (s. l.), which supports Agatha's classification based on morphological characters; (2) the families Tontoniidae and Cyrtostrombidiidae are both monophyletic whereas Strombidiidae is polyphyletic; (3) the positions of the families Cyrtostrombidiidae and Pelagostrombidiidae varied in different trees although with low support values; (4) the close relationship between Varistrombidium and Apostrombidium is confirmed, which updates the evolutionary hypothesis for oligotrichs based on ciliary patterns; and (5) two relatively stable clades were found in the family Strombidiidae.

Updating Biodiversity Studies in Loricate Protists: The Case of the Tintinnids (Alveolata, Ciliophora, Spirotrichea).

Species determination is crucial in biodiversity research. In tintinnids, identification is based almost exclusively on the lorica, despite its frequent intraspecific variability and interspecific similarity. We suggest updated procedures for identification and, depending on the aim of the study, further steps to obtain morphological, molecular, and ecological data. Our goal is to help improving the collection of information (e.g. species re-/descriptions and DNA barcodes) that is essential for generating a natural tintinnid classification and a reliable reference for environmental surveys. These suggestions are broadly useful for protistologists because they exemplify data integration, quality/effort compromise, and the need for scientific collaborations.

Clinical Outcomes of Infants With Periorbital Hemangiomas Treated With Oral Propranolol.

PURPOSE: Periorbital infantile hemangiomas (IHs) require early intervention because they have the potential risk of causing visual disturbances. In recent years, propranolol has shown promise in the effective management of periocular and periorbital IHs. The objective of our study was to assess the clinical outcomes, efficacy, and safety of propranolol in the management of infants with high-risk periorbital IHs. PATIENTS AND METHODS: This retrospective study was conducted at the Stomatological Hospital affiliated with China Medical University. The medical records of infants with periorbital hemangiomas who were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg per day between January 2014 and June 2015 were reviewed. We excluded infants who did not qualify for propranolol treatment and infants who received previous therapy or other treatments. The records were reviewed for treatment response, adverse events during treatment, length of treatment, and recurrences. Treatment response was classified using a 4-point scale system based on reduction in volume as poor (<25%), moderate (25 to 50%), good (50 to 75%), or excellent (>75 to 100%) and change in color, as well as surface texture, by a panel of 3 plastic surgeons using 2-dimensional photographs, clinical examination, and Doppler ultrasonography measurements taken before and after treatment. RESULTS: Of 38 infants with periorbital hemangiomas, 26 were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg administered once daily. A total of 11 male and 15 female infants with a mean age of 5.2 months (range, 2 to 12 months) were treated. The mean length of treatment was 22 weeks (range, 4 to 41 weeks). Adverse events of diarrhea (n = 3) and sleep changes (n = 1) were encountered during treatment in 4 patients. The overall treatment response was scored as excellent in 17 patients, good in 7, moderate in 2, and poor in 0. No patients required discontinuation of treatment because of adverse events, and there were no cases of recurrence or tumor regrowth noted during the mean follow-up period of 6.5 months (range, 3 to 10 months). CONCLUSIONS: Oral propranolol at a dose of 1.0 to 1.5 mg/kg per day (age ≤3 months, 1.0 mg/kg; age >3 months, 1.5 mg/kg) was effective and well tolerated for the management of 26 Chinese infants with high-risk periorbital IHs. Early intervention should be considered to reduce risk of visual impairment and improve esthetic outcomes.

Oral Propranolol for the Treatment of Infantile Hemangiomas in the Post-Proliferative Phase: A-Single Center Retrospective Study of 31 Cases.

PURPOSE: Infantile hemangiomas (IHs) are the most common benign tumors affecting infants, and most IHs are self-limiting. However, there are cases that require specific treatment. Propranolol is now widely used to treat severe IHs. Several studies have shown the efficacy and limited side effects associated with propranolol as the first-line treatment for IHs. There are a limited number of publications describing the role of propranolol in treating IHs beyond the proliferative phase (>12 months). The purpose of this study was to evaluate the effects and safety of oral high-dose (2.0 mg/kg per day) propranolol for IHs beyond the proliferative phase (>12 months). PATIENTS AND METHODS: This study enrolled patients with IHs who accepted systemic propranolol treatment from the Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated China Medical University. This is a single-center retrospective study conducted from April 2011 to July 2015. All children who were older than 12 months were eligible for the study. Digital photographs taken before and after treatment were analyzed by a panel of 3 plastic surgeons. The esthetic results were evaluated using a 4-point scale and ranked as poor, moderate, good, or excellent. The patient follow-up visits were scheduled monthly, and changes in the size, texture, and color of the lesions were recorded. The adverse effects after medication were evaluated and managed accordingly. RESULTS: We collected data on 31 eligible patients. The 31 patients had 32 hemangiomas (1 female patient had 2 lesions) and were treated with systemic propranolol at a high dose of 2 mg/kg per day. The mean age at the initiation of propranolol therapy was 18.4 months (range, 12 to 48 months), and the mean treatment duration was 10.1 months (range, 8 to 16 months). The treatment responses for the 32 hemangiomas included 17 excellent responses (53.1%), 8 good responses (25%), and 7 moderate responses (21.9%). There were no severe side effects encountered and recurrence was observed in 3 patients during the treatment and follow-up course. CONCLUSIONS: Oral propranolol, 2 mg/kg per day, is a safe and effective treatment for IHs beyond the proliferative phase (>12 months of age) in the Chinese population.