Aerobic Oxidative Desulfurization by Supported Polyoxometalate Ionic Liquid Hybrid Materials via Facile Ball Milling.

With the increasingly strict limitations on emission standards of vehicles, deep desulfurization in fuel is indispensable for social development worldwide. In this study, a series of hybrid materials based on SiO2-supported polyoxometalate ionic liquid were successfully prepared via a facile ball milling method and employed as catalysts in the aerobic oxidative desulfurization process. The composition and structure of prepared samples were studied by various techniques, including FT-IR, UV-vis DRS, wide-angle XRD, BET, XPS, and SEM images. The experimental results indicated that the synthesized polyoxometalate ionic liquids were successfully loaded on SiO2 with a highly uniform dispersion. The prepared catalyst (C16PMoV/10SiO2) exhibited good desulfurization activity on different sulfur compounds. Moreover, the oxidation product and active species in the ODS process were respectively investigated via GC-MS and ESR analysis, indicating that the catalyst can activate oxygen to superoxide radicals during the reaction to convert DBT to its corresponding sulfone in the fuel.

Multi-Layer Graph Attention Network for Sleep Stage Classification Based on EEG.

Graph neural networks have been successfully applied to sleep stage classification, but there are still challenges: (1) How to effectively utilize epoch information of EEG-adjacent channels owing to their different interaction effects. (2) How to extract the most representative features according to confused transitional information in confused stages. (3) How to improve classification accuracy of sleep stages compared with existing models. To address these shortcomings, we propose a multi-layer graph attention network (MGANet). Node-level attention prompts the graph attention convolution and GRU to focus on and differentiate the interaction between channels in the time-frequency domain and the spatial domain, respectively. The multi-head spatial-temporal mechanism balances the channel weights and dynamically adjusts channel features, and a multi-layer graph attention network accurately expresses the spatial sleep information. Moreover, stage-level attention is applied to easily confused sleep stages, which effectively improves the limitations of a graph convolutional network in large-scale graph sleep stages. The experimental results demonstrated classification accuracy; MF1 and Kappa reached 0.825, 0.814, and 0.775 and 0.873, 0.801, and 0.827 for the ISRUC and SHHS datasets, respectively, which showed that MGANet outperformed the state-of-the-art baselines.

Hybrid zeolite-based ion-exchange and sulfur oxidizing denitrification for advanced slaughterhouse wastewater treatment.

The discharge of slaughterhouse wastewater (SWW) is increasing and its wastewater has to be treated thoroughly to avoid the eutrophication. The hybrid zeolite-based ion-exchange and sulfur autotrophic denitrification (IX-AD) process was developed to advanced treat SWW after traditional secondary biological process. Compared with traditional sulfur oxidizing denitrification (SOD), this study found that IX-AD column showed: (1) stronger ability to resist NO3- pollution load, (2) lower SO42- productivity, and (3) higher microbial diversity and richness. Liaoning zeolites addition guaranteed not only the standard discharge of NH4+-N, but also the denitrification performance and effluent TN. Especially, when the ahead secondary biological treatment process run at the ultra-high load, NO3--N removal efficiency for IX-AD column was still ~100%, whereas only 64.2% for control SOD column. The corresponding average effluent TN concentrations for IX-AD and SOD columns were 5.89 and 65.55 mg/L, respectively. Therefore, IX-AD is a promising technology for advanced SWW treatment and should be widely researched and popularized.

Individualized surgery combined with radiotherapy and triamcinolone acetonide injection for the treatment of auricular keloids.

BACKGROUND: Although multiple methods have been proposed to treat auricular keloids, low curative effects and high recurrence rates are currently major clinical problems. Thereinto, surgery combined with radiotherapy and triamcinolone acetonide injection is considered to be the proper choice for comprehensive treatment of auricular keloids. This study aimed at evaluating the therapeutic effect of individualized surgery combined with radiotherapy for the treatment of auricular keloids. METHODS: From February 2014 to February 2017, 67 patients with 113 auricular keloids in total were enrolled in this study. According to specific conditions of lesions, the local tissue and patients' individual wishes, different surgical methods were selected to analyze the scar excision and repairment of the defect. Within 24 h after the keloid was excised, 5 MeV electron beam irradiation by the linear accelerator was used by radiotherapy with a total dose of 20 Gy at interval of 1 day for 10 consecutive times. Triamcinolone acetonide was injected immediately after surgery, and per month afterward in the following three months. RESULTS: 113 keloids in total were received treatment. The follow-up period was 24 months. Fourteen keloids (12.39%) showed subjective recurrence with a success rate of 87.61%. Wilcoxon matched-pairs rank-sum test was used to compare the differences of the 24-month postoperative VSS scores and the preoperative VSS scores. The VSS scores were as follows: 82 keloids (72.57%) scored less than 5 points (good result), 21 keloids (18.58%) scored 6 to 10 points (fair result), and only 10 keloids (8.85%) scored more than 10 points (bad result). The effective rate was 91.15%. CONCLUSIONS: Individualized surgery combined with early postoperative radiotherapy and triamcinolone acetonide injection is an ideal treatment method to ensure good auricular appearance, low incidences of complications and recurrence based on effective treatment of auricular keloids.

Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells.

Exosomes exhibit great therapeutic potential in bone tissue engineering. The study aimed to investigate whether the exosomes derived from human adipose-derived stem cells (hADSCs-Exos) during different time-span of osteogenic differentiation could promote osteogenesis. The appropriate concentrations of hADSCs-Exos to enhance the proliferation, migration and osteogenesis of hADSCs-Exos were also examined. PKH67 labelled hADSCs-Exos was used to detect the internalization ability of hADSCs. The osteogenic differentiation abilities of hADSCs after treatment with hADSCs-Exos was evaluated by Alizarin red staining (ARS). The proliferation and migration of hADSCs was examined by cell counting kit-8 and wound healing assay, respectively. The expression of exosomal surface markers and osteoblast-related protein of hADSCs was assessed by Western blot. PKH67-labelled exosomes were internalized by hADSCs after 4 h incubation. ARS showed that the amount of mineralized nodules in Exo1-14d group was significantly higher than that in Exo15-28d group. hADSCs-Exos could promote the proliferation and migration capacity of hADSCs. Western blot analysis showed that after hADSCs-Exos treatment, ALP and RUNX2 were significantly enhanced. Specially, the Exo1-14d group of 15 µg/mL significantly upregulated the expression of RUNX2 than the other exosomes treated groups. Our findings suggest that exosomes secreted by hADSCs during osteogenic induction for 1-14 days could be efficiently internalized by hADSCs and could induce osteogenic differentiation of hADSCs. Moreover, administration of Exo1-14d at 15 µg/mL promoted the proliferation and migration of hADSCs. In conclusion, our research confirmed that comprised of hADSCs-Exos and hADSCs may provide a new therapeutic paradigm for bone tissue engineering.

Evaluation of advanced phosphorus removal from slaughterhouse wastewater using industrial waste-based adsorbents.

Slaughterhouse wastewater (SWW) contains high concentrations of phosphorus (P) and is considered as a principal industrial contaminant that causes eutrophication. This study developed two kinds of economical P removal adsorbents using flue gas desulfurization gypsum (FGDG) as the main raw material and bentonite, clay, steel slag and fly ash as the additives. The maximum adsorption capacity of the adsorbent composed of 60% FGDG, 20% steel slag, and 20% fly ash (DSGA2) was found to be 15.85 mg P/g, which was 19 times that of the adsorbent synthesized using 60% FGDG, 30% bentonite, and 10% clay (DSGA1) (0.82 mg P/g). Surface adsorption, internal diffusion, and ionic dissolution co-existed in the P removal process. The adsorption capacity of DSGA2 (2.50 mg P/g) was also evaluated in column experiments. The removal efficiency was determined to be higher than 92% in the first 5 days, while the corresponding effluent concentration was lower than the Chinese upcoming SWW discharge limit of 2 mg P/L. Compared with DSGA1, DSGA2 (synthesized from various industrial wastes) showed obvious advantages in improving adsorption capacity of P. The results showed that DSGA2 is a promising adsorbent for the advanced removal of P from SWW in practical applications.

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma.

Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycling phenotype. Furthermore, we explored the cause of how and why miR-152-5p affected metastasis in depth. Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAFV600-mutant melanoma patients.

Pressure-induced ionic to mixed ionic and electronic conduction transition in solid electrolyte LaF3.

The ionic transport properties of solid electrolyte LaF3 were systematically studied under high pressures up to 30.6 GPa with alternate-current impedance spectra measurements and first-principles calculations. From the impedance spectra measurements, LaF3 was found to transform from pure ionic conduction to mixed ionic and electronic conduction at 15.0 GPa, which results from the pressure-induced structural phase transition from a tysonite-type structure to an anti-Cu3Ti-type structure. F- ion migration can be suppressed by pressure, causing a decrease of the ionic conductivity of LaF3. By first-principles calculations, the pressure-dependent diffusion behaviors of the F- ions can be understood. The increased overlap of electron clouds at the interstitial site between rigid La3+ and liquid F- lattices leads to the appearance of electronic conduction in anti-Cu3Ti-type structured LaF3.

The Effects of Timing of Postoperative Radiotherapy on Hypertrophic Scar in a Rabbit Model.

BACKGROUND Hypertrophic scar is associated with excessive proliferation of fibroblasts, the accumulation of collagen fibers, and angiogenesis associated with chronic inflammation. Scar resection, combined with radiotherapy, is widely used in clinical practice, but timing remains controversial. This study aimed to investigate the association between the timing of postoperative radiotherapy and the effects on hypertrophic scar in a rabbit model. MATERIAL AND METHODS Forty New Zealand white rabbits, 8-12 months old, weighing 1.8-2.3 kg were used in the model of hypertrophic scar and underwent surgical resection with or without postoperative radiotherapy. The study groups included: Group 1, the non-resection group; Group 2, the resection and non-radiotherapy group; Group 3, the immediate postoperative radiotherapy group; Group 4, the 12-hour postoperative radiotherapy group; Group 5, the 24-hour postoperative radiotherapy group; Group 6, the 48-hour postoperative radiotherapy group; Group 7, the 72-hour postoperative radiotherapy group; and Group 8, the 120-hour postoperative radiotherapy group. The rabbit ear skin was observed after treatment, and the hypertrophic scar index (HI), fibroblast numerical area density (NA), and collagen fiber area density (AA) were determined. RESULTS The HI, NA, and AA were significantly lower after 48 hours of postoperative radiotherapy (P<0.05), with the effects occurring mainly within 24 hours. There was no difference in HI, NA, and AA between the radiotherapy and non-radiotherapy groups within 24 hours after surgery. CONCLUSIONS In a rabbit model of hypertrophic scar, surgical resection combined with radiotherapy resulted in an optimal effect within 24 hours after surgery.

Performance enhancement of H2S-based autotrophic denitrification with bio-gaseous CO2 as sole carbon source through new pH adjustment materials.

H2S-based denitrification could achieve synchronous removal of nitrate and H2S and had been regarded as an efficient way for biogas desulfurization and wastewater denitrification. Using CO2 in biogas as carbon source had a potential of saving cost further, but the performance deteriorated due to the drop in pH. Two kinds of nature ore, medical stone and phosphate ore, were added as new pH adjustment materials in this study, and feasibility of using CO2 as sole carbon source for H2S-based denitrification was investigated. As a result, both materials could increase the pH from 4.5 to above 6.0. Compared with medical stone, higher level of pH (up to 6.39) and nitrate removal efficiency (99.1%) were obtained with phosphate ore. In addition, ATP increased more rapidly than the control, reflecting improvement on microbial activities. Therefore, phosphate ore as the pH adjustment material could improve H2S-based denitrification performance obviously.

Stimulation impact of electric currents on heterotrophic denitrifying microbial viability and denitrification performance in high concentration nitrate-contaminated wastewater.

Electric current stimulation has been shown to have a positive influence on heterotrophic denitrifying microbial viability and has the potential to improve wastewater denitrification performance. This study investigated the effects of varying current densities on microbial activity and NO3- removal efficiency under heterotrophic conditions.NO3- removal rate was highest at an applied current density of 400 mA/m2. However, the optimum removal efficiency of total inorganic nitrogen (TIN; 99%) was achieved when the current density was fixed at 200 mA/m2. Accumulation of NH4+-N and NO2--N byproducts were also minimized at this current density. The activity of heterotrophic denitrifying microorganisms was much higher at both 200 and 400 mA/m2. Moreover, the average adenosine-5'-triphosphate (ATP) content (an indicator of cell metabolism) at a current density of 1600 mA/m2 was lower than that under no current, indicating heterotrophic denitrifying microbial activity can be inhibited at high current densities. Hence, direct electrical stimulation on the activity of heterotrophic denitrifying microorganisms in the developed system should be lower than 1600 mA/m2. This study improves the understanding of electric current influence on heterotrophic denitrifying microorganisms and promotes the intelligent application of direct electrical stimulation on wastewater treatment processes.

NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma.

UNLABELLED: Epstein-Barr virus (EBV) expresses few viral proteins in nasopharyngeal carcinoma (NPC) but high levels of BamHI-A rightward transcripts (BARTs), which include long noncoding RNAs (lncRNAs) and BART microRNAs (miRNAs). It is hypothesized that the mechanism for regulation of BARTs may relate to EBV pathogenesis in NPC. We showed that nuclear factor-κB (NF-κB) activates the BART promoters and modulates the expression of BARTs in EBV-infected NPC cells but that introduction of mutations into the putative NF-κB binding sites abolished activation of BART promoters by NF-κB. Binding of p50 subunits to NF-κB sites in the BART promoters was confirmed in electrophoretic mobility shift assays (EMSA) and further demonstrated in vivo using chromatin immunoprecipitation (ChIP) analysis. Expression of BART miRNAs and lncRNAs correlated with NF-κB activity in EBV-infected epithelial cells, while treatment of EBV-harboring NPC C666-1 cells with aspirin (acetylsalicylic acid [ASA]) and the IκB kinase inhibitor PS-1145 inhibited NF-κB activity, resulting in downregulation of BART expression. Expression of EBV LMP1 activates BART promoters, whereas an LMP1 mutant which cannot induce NF-κB activation does not activate BART promoters, further supporting the idea that expression of BARTs is regulated by NF-κB signaling. Expression of LMP1 is tightly regulated in NPC cells, and this study confirmed that miR-BART5-5p downregulates LMP1 expression, suggesting a feedback loop between BART miRNA and LMP1-mediated NF-κB activation in the NPC setting. These findings provide new insights into the mechanism underlying the deregulation of BARTs in NPC and identify a regulatory loop through which BARTs support EBV latency in NPC. IMPORTANCE: Nasopharyngeal carcinoma (NPC) cells are ubiquitously infected with Epstein-Barr virus (EBV). Notably, EBV expresses very few viral proteins in NPC cells, presumably to avoid triggering an immune response, but high levels of EBV BART miRNAs and lncRNAs which exhibit complex functions associated with EBV pathogenesis. The mechanism for regulation of BARTs is critical for understanding NPC oncogenesis. This study provides multiple lines of evidence to show that expression of BARTs is subject to regulation by NF-κB signaling. EBV LMP1 is a potent activator of NF-κB signaling, and we demonstrate that LMP1 can upregulate expression of BARTs through NF-κB signaling and that BART miRNAs are also able to downregulate LMP1 expression. It appears that aberrant NF-κB signaling and expression of BARTs form an autoregulatory loop for maintaining EBV latency in NPC cells. Further exploration of how targeting NF-κB signaling interrupts EBV latency in NPC cells may reveal new options for NPC treatment.

Comparison of particulate pyrite autotrophic denitrification (PPAD) and sulfur oxidizing denitrification (SOD) for treatment of nitrified wastewater.

The use of reduced sulfur compounds as electron donors for biological denitrification has the potential to reduce chemical and sludge disposal costs as well as carry-over of organic carbon to the effluent that often occurs with heterotrophic denitrification. Although a number of prior studies have evaluated sulfur oxidizing denitrification (SOD), no prior studies have evaluated particulate pyrite autotrophic denitrification (PPAD) in continuous flow systems. Bench-scale upflow packed bed reactors (PBRs) were set up to compare denitrification rates, by-product production and alkalinity consumption of PPAD and SOD. At an empty bed contact time of 2.9 h, average NO3--N removal efficiencies were 39.7% and 99.9% for PPAD and SOD, respectively. Although lower denitrification rates were observed with PPAD than SOD, lower alkalinity consumption and reduced sulfur by-product formation (SO42-, S2- and SO32- plus S2O32-) were observed with PPAD. Furthermore, higher denitrification rates and lower by-product production was observed for SOD than in prior studies, possibly due to the media composition, which included sand and oyster shells. The results show that both pyrite and elemental sulfur can be used as electron donors for wastewater denitrification in PBRs.

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.

Synthesis of the New-Type Vascular Endothelial Growth Factor-Silk Fibroin-Chitosan Three-Dimensional Scaffolds for Bone Tissue Engineering and In Vitro Evaluation.

The objective of the study was to discuss the biocompatibility of the vascular endothelial growth factor-silk fibroin-chitosan (VEGF-SF-CS) scaffolds. To offer an ideal scaffold for bone tissue engineering, the author added vascular endothelial growth factor (VEGF) into silk fibroin-chitosan (SF-CS) scaffold directly to reconstruct a three-dimensional scaffold for the first time, SF-CS scaffold was loaded with VEGF and evaluated as a growth factor-delivery device. Human fetal osteoblast cell was seeded on the VEGF-SF-CS scaffolds and SF-CS scaffolds. On VEGF-SF-CS and SF-CS scaffolds, the cell adhesion rate was increased as time went on. Scanning electron microscopy: the cells grew actively and had normal multiple fissions, granular and filamentous substrates could be seen around the cells, and cell microfilaments were closely connected with the scaffolds. The cells could not only show the attached growth on surfaces of the scaffolds, but also extend into the scaffolds. Cell Counting Kit-8 and alkaline phosphatase analysis proved that the VEGF could significantly promote human fetal osteoblast1.19 cells growth and proliferation in the SF-CS scaffolds, but the enhancement of osteoblasts cell proliferation and activity by VEGF was dependent on time.

Oral Propranolol With Topical Timolol Maleate Therapy for Mixed Infantile Hemangiomas in Oral and Maxillofacial Regions.

PURPOSE: The combination treatment for mix infantile hemangiomas (IHs) using oral propranolol with topical timolol maleate was not well documented in the literature. The aim of this study was to evaluate the therapeutic effects and safety of oral propranolol along with topical timolol maleate or oral propranolol alone for treating mixed IHs in the oral and maxillofacial regions. METHODS: Between March 2013 and June 2014, a total of 31 patients with mixed IHs in the oral and maxillofacial regions were recruited to the study and randomly divided into experimental and control groups. Fourteen patients in the experimental group (A) were treated with oral proranolol in combination with topical timolol maleate, and 17 patients in the control group (B) underwent orally proranolol treatment alone. The maximal treatment duration was planned for 8 months. Ultrasonography and serial photographs based on Visual Analogue Scale (VAS) were used to assess the effects of treatment before and after treatment, as well as adverse effects after medication were evaluated and managed accordingly. RESULTS: All patients completed treatment. Among the most patients, there was obvious fading of color or decrease in size of the IHs when compared with pretreatment. There was significant reduction of color fading in A (mean VAS score: 8.36 ± 1.39) than that in B (7.18 ± 1.71) (P = 0.043) after the end of treatment, whereas the reduction of sizes in A (8.00 ± 1.75) had no significant difference than that in B (7.59 ± 1.80) (P= .51). The treatment duration of A (5.64 ± 1.45) was shorter than that of B (6.71 ± 1.10) (P= .037). No major collateral effects were observed in both the groups throughout the course of treatment. CONCLUSIONS: Oral proranolol combined with topical timolol maleate was well tolerated and effective treatment, mild side effects, and especially gave rise to better clinical response in the treatment of mixed IHs than oral propranolol alone.

Circulating Epstein-Barr virus microRNAs miR-BART7 and miR-BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment.

More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein-Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV-harboring NPC and noncancerous NP cells found that miR-BART3, miR-BART7 and miR-BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n = 89), and healthy (n = 28) and non-NPC tumor patient controls (n = 18) found levels of both miR-BART7 and miR-BART13, but not miR-BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR-BART7 and miR-BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miR-BART13, but not miR-BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR-BART7 and miR-BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy.

Topical timolol maleate for superficial infantile hemangiomas: an observational study.

PURPOSE: The objective of this study was to assess the clinical effects and safety of topical timolol maleate for the management of superficial infantile hemangiomas (IHs). MATERIALS AND METHODS: From October 2012 to March 2014, 35 infants (24 girls and 11 boys; 2 to 10 months old; median age, 4.7 months) with superficial hemangiomas were treated with the local application of timolol maleate in the authors' department. Thirty-five lesions were treated using topically administrated timolol maleate every 12 hours for a mean duration of 22 weeks (range, 6 to 45 weeks). Follow-up visits were scheduled monthly and changes in tumor size, texture, and color were recorded. Treatment response was scored according to a 3-point scale system as good, partial, or no response. Adverse effects after medication were evaluated and managed accordingly. RESULTS: All patients completed treatment. Of the 35 hemangiomas, 18 (51.4%) showed a good response, 10 (31.4%) showed a partial response, and 6 (17.2%) had no response. The total response rate was 82.8% (29 of 35). Clinically, no systemic or local side effects caused by timolol maleate were observed in the patients. CONCLUSIONS: Topical timolol maleate could provide an effective and safe alternative to the systemic use of propranolol for the treatment of superficial IHs. Further prospective studies are needed to confirm the efficacy and safety of topical timolol maleate for the treatment of IHs.

Treatment of severe infantile hemangiomas with propranolol: an evaluation of the efficacy and effects of cardiovascular parameters in 25 consecutive patients.

PURPOSE: The aim of this study was to investigate the therapeutic results and effects of propranolol on cardiovascular parameters in infants receiving systemic propranolol for complicated infantile hemangiomas (IHs), as well as to evaluate the adverse effects of propranolol throughout the course of treatment. MATERIALS AND METHODS: Twenty-five consecutive patients who presented with complicated IHs were prospectively recruited into this study between April 2012 and June 2013. All patients were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg, and the drug was taken once per day. The length of treatment was 8.2 months on average and ranged from 6 to 12 months. The follow-up visits were scheduled monthly after discharge. Changes were recorded during the 3-day hospitalization, including systolic and diastolic blood pressures, heart rate, and blood glucose level. The treatment responses were scored according to a 4-point scale system as very good, good, mild, or no response. The adverse effects after medication administration were evaluated and managed accordingly. RESULTS: Of the 25 patients, 8 (32%) had a very good response, 11 (44%) had a good response, and 6 (24%) had a mild response. When pretreatment and post-treatment values were compared, there was no significant decrease in mean systolic and diastolic blood pressures and mean heart rate (all P > .05). The decreases in the cardiovascular parameters were not commonly associated with observable clinical symptoms. No major collateral effects were observed, and no infants were withdrawn from treatment because of side effects. CONCLUSIONS: Fluctuations from the normal ranges of cardiovascular parameters occurred frequently with the initiation of propranolol, but were clinically asymptomatic. Therefore oral propranolol was an effective and safe treatment for IHs, particularly for early intervention suitable for severe IHs.

First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study.

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).