MicroRNA­203a­3p improves bleomycin and pingyangmycin sensitivity by inactivating the PI3K/AKT pathway in hemangioma.

MicroRNAs (miRs) have been found to play a fundamental role in the pathology and progression of hemangioma. Of note, miR-203a-3p prevents hemangioma progression via inactivation of the PI3K/AKT pathway. Bleomycin and pingyangmycin are drugs used in sclerotherapy, but certain hemangioma patients experience drug resistance, leading to poor clinical outcomes. The present study aimed to explore the impact of miR-203a-3p on bleomycin and pingyangmycin sensitivity in hemangioma, as well as the involvement of the PI3K/AKT pathway. miR-203a-3p or negative control mimics were transfected into human hemangioma endothelial cells, which were treated with 0-20 µM bleomycin or pingyangmycin. Subsequently, 740 Y-P, a PI3K/AKT pathway agonist, was added. Cell viability, rate of apoptosis and the expression levels of proteins involved in the PI3K/AKT pathway, including phosphorylated (p)-PI3K, PI3K, p-AKT and AKT, were detected. miR-203a-3p overexpression significantly decreased the half-maximal inhibitory concentration (IC50) values of bleomycin (5.84±0.87 vs. 14.23±2.17 µM; P<0.01) and pingyangmycin (5.13±0.55 vs. 12.04±1.86 µM; P<0.01), compared with untreated cells. In addition, under bleomycin or pingyangmycin treatment, miR-203a-3p overexpression significantly reduced the proportion of EdU positive cells (both P<0.05) and B-cell leukemia/lymphoma-2 (BCL2) protein expression levels (both P<0.05), whilst increasing cell apoptosis rate (both P<0.05) and cleaved caspase 3 protein expression levels (both P<0.05) compared with untreated controls. Furthermore, miR-203a-3p overexpression significantly inhibited the phosphorylation of PI3K and AKT (both P<0.05), an effect that was significantly diminished by 740 Y-P treatment (both P<0.01). In addition, 740 Y-P significantly increased IC50 values of bleomycin (P<0.01) and pingyangmycin (P<0.001) and also significantly increased the proportion of EdU-positive cells and BCL2 protein expression levels, while decreasing the apoptosis rate and cleaved caspase 3 protein expression levels in cells treated with bleomycin or pingyangmycin (all P<0.05). Of note, 740 Y-P weakened the effect of miR-203a-3p overexpression on the aforementioned cellular characteristics. The present study demonstrated that miR-203a-3p improved the sensitivity of cells to bleomycin and pingyangmycin treatment by inhibiting PI3K/AKT signaling in hemangioma.

Intralesional injection of bleomycin in the management of low flow vascular malformations: Results and factors affecting the outcome.

OBJECTIVE: Ethanol has been a commonly used sclerosant for low-flow vascular malformations, but it carries a high risk of complications. Bleomycin has been recently introduced as a potentially effective treatment. The aim of this study was to evaluate the safety and efficacy of bleomycin intralesional injection for the treatment of low-flow vascular malformations and determine the different factors affecting the outcome. PATIENTS AND METHODS: A total of fifty patients with low-flow vascular malformations were enrolled in the study between April 2020 and March 2022. All patients underwent preoperative duplex ultrasound and magnetic resonance angiography. The procedure was performed under ultrasound and fluoroscopic guidance. All patients were assessed for the objective improvement, ultrasound assessment, and patient-reported outcome. RESULTS: The overall rate of objective improvement was 79.53% (78.05% in venous and 87.5% in lymphatic malformations), whereas 81.25% of the patients showed a degree of size reduction or complete obliteration on postoperative ultrasound. The patient-reported outcome analysis showed a statistically significant improvement in the mean score for the pain, overall symptoms, and self-confidence. On regression analysis, the only factor associated with poor objective outcome was diffuse lesions (ill-defined or extending in more than one body region or one compartment). No major complications were recorded. CONCLUSIONS: Bleomycin intralesional injection is a safe and effective treatment for low-flow vascular malformations.

A nomogram for predicting sclerotherapy response for treatment of lymphatic malformations in children.

PURPOSE: In this manuscript, we purposed to identify the prognostic factors for treatment of lymphatic malformations in children using polidocanol foam combined with pingyangmycin and to construct nomogram for predicting sclerotherapy response. METHODS: A retrospective analysis of 77 children having LMs who underwent sclerotherapy using polidocanol foam combined with pingyangmycin under ultrasound display from January 2017 to April 2020 was done. The clinical response was graded as excellent (≥ 90%), good (≥ 50%, < 90%), and poor (< 50%). More than 50% was considered as acceptable response. Prognostic factors were identified by Pearson's Chi-square or Fisher's exact test and multivariable logistic regression model was used to construct a nomogram to predict sclerotherapy response. The discrimination and calibration of nomogram were verified through the receiver operating characteristic cure and calibration plots. RESULTS: The mean number of treatment sessions was 3.1 (range, 1-6). Among 77 patients, 58 patients (75.3%) had excellent response to treatment (≥ 90%) and 68 patients (88.3%) had an acceptable response (≥ 50%, < 90%). Clinical disfigurement (P = 0.014), skin discoloration (P = 0.040), morphological subtype (P < 0.001) and extent of the lesion (P < 0.001) correlated with clinical response to sclerotherapy in LMs. Sclerotherapy response was predicted through nomogram constructed in this study, which shows good calibration and discrimination. Also, focal lesion and macrocystic or mixed morphological subtype lesion were seen more often in lower number of treatment sessions among the patients with excellent response. CONCLUSIONS: An acceptable response to sclerotherapy using polidocanol foam combined with pingyangmycin was achieved in majority of LMs in children with extremely low complication rates. Nomogram based on the prognostic factors of sclerotherapy response for LMs in children was shown to possess an excellent performance to predict the probability of LMs sclerotherapy response.

A Comparison of Potassium Titanyl Phosphate Laser and Pingyangmycin as Treatment for Adult Laryngeal Hemangioma.

Objective: To evaluate the curative effect of Potassium titanyl phosphate (KTP) laser and pingyangmycin injection for adult laryngeal hemangiomas (ALH). Methods: This was a retrospective study conducted on patients treated with either KTP laser or pingyangmycin injection to assess the efficacy of both treatment and compare the effects on different types of adult laryngeal hemangioma. Results: The ordinal logistic regression test showed the surgery methods had no effect on the therapeutic results. On the contrary, the shape of ALH and the interaction between surgical procedures and ALH shape affected the prognosis of the ALH. This meant that the shape of ALH might be a confounding factor affecting the therapeutic effect of ALH. Thus, the Cochran-Mantel-Haenszel test which is a stratification analysis was used to assess the interaction between surgical procedures and ALH shape. Then better results were achieved using the KTP laser for the plane and raised types of ALH. Conclusions: The selection of surgical procedures (the KTP laser or pingyangmycin injection approaches) affects the treatment of ALH. For plane and raised ALH, the KTP laser may be recommended.

Successful Sclerotherapy for Cervicofacial Macrocystic Lymphatic Malformations Using Polidocanol and Pingyangmycin Combined Foam Sclerosants.

Background: Sclerotherapy is the first-line therapeutic method for lymphatic malformations (LMs). This retrospective cohort study evaluated the effectiveness and safety of a novel combined foam sclerosant: polidocanol and pingyangmycin foam (PPF), for treating cervicofacial macrocystic LMs. Methods and Results: From July 2018 to October 2020, 51 patients with cervicofacial macrocystic LMs were enrolled in this study. All patients received intralesional 3% polidocanol or PPF injections. The outcome was evaluated regarding demographic and clinical characteristics, degree of treatment response, and post-treatment complications. Overall, 16 patients (31.4%) underwent PPF sclerotherapy. All these patients (100%) showed remarkable reduction in lesion size within three sessions. Excellent responses were shown in 88.5% of these patients within three sessions, which is higher than single polidocanol sclerotherapy (80%). The average sessions (duration) of PPF sclerotherapy were 2.5, which was significantly shorter than the single foam sclerotherapy (p < 0.05). Treatment duration was significantly associated with age, lesion location, lesion size, and number of cysts (p < 0.05). No severe complications were noted in this study. Local or systemic complications, such as swelling and mild fever occurred but subsided without any specific treatment. Conclusions: PPF is a safe, and effective combined foam sclerosant for the treatment of cervicofacial macrocystic LMs. This combined foam can improve treatment response and reduce treatment duration compared with a single sclerosant. It can be broadly used if further large-scale clinical trials verify its efficacy and safety.

Animal experimental research of intralesional bleomycin and pingyangmycin in the treatment of xanthoma.

BACKGROUND: Xanthelasma palpebrarum is a type of human xanthoma that occurs on the skin of human eyelids and is a benign skin lesion. Pingyangmycin (also known as bleomycin A5) is one of the 13 components of bleomycin. The aim of this study was to explore the efficacy of intralesional bleomycin and pingyangmycin in the treatment of xanthoma based on histopathological observations in animal experimental research. METHODS: An animal model of xanthoma was established by feeding rabbits with a high-cholesterol diet. Pingyangmycin and bleomycin interfered with the skin xanthoma of the animal model. Skin tissue specimens were stained with hematoxylin-eosin and oil red O to evaluate the effect of the intervention. RESULTS: A xanthoma animal model was established. Pingyangmycin and bleomycin could reduce the abnormal lipid deposition in the lesion area of the skin xanthoma of the animal, via a local injection. In addition, pingyangmycin was more effective than bleomycin in eliminating lipid deposition in rabbit skin xanthoma.

Clinical evaluation and animal experimental study of different mass concentrations of pingyangmycin in the local injection treatment of lip venous malformation.

BACKGROUND: This study investigated the clinical efficacy of different mass concentrations of pingyangmycin in the local injection treatment of lip venous malformation. An animal experimental study of the histopathological effects of different mass concentrations of pingyangmycin on the normal lip tissue of rabbits was also conducted. METHODS: (I) We retrospectively analysed 98 out-patients with lip venous malformation in the Stomatological Hospital and the Fourth Affiliated Hospital of China Medical University from January 2008 to June 2013. The 98 cases were treated by local injection of different mass concentrations (8 mg/3 mL and 8 mg/5 mL) of pingyangmycin for the different sites of the lips. The clinical efficacy was observed, and adverse reactions were recorded. (II) 60 healthy male rabbits were randomly divided into three groups: a 8 mg/5 mL pingyangmycin group, a 8 mg/3 mL pingyangmycin group, and a control group. The right upper lips of the experimental groups were injected with 1ml pingyangmycin (8 mg/5 mL) and 1ml pingyangmycin (8 mg/3 mL) respectively, and the control group was injected with the same volume of normal saline. The thickness of the right upper lip of rabbits in the experimental groups and the control group was measured on the 21st, 28th, 35th, and 60th days after the first injection. Histopathological changes at the injection site were observed by light microscope and transmission electron microscope. RESULTS: Venous malformations involving the skin tissues of the lips (pingyangmycin 8 mg/3 mL) had an effective rate of 93.62%, and those involving the labial mucosa tissues (pingyangmycin 8 mg/5 mL) had an effective rate of 98.04%. In the animal experiment, there were statistically significant differences in the thickness of the injection site among the 8 mg/3 mL group, 8 mg/5 mL group, and the control group at different time points (P<0.01). CONCLUSIONS: The local injection of pingyangmycin in the treatment of lip venous malformations was efficient, safe and reliable. In the process of clinical application, attention should be paid when the concentration is 8 mg/3 mL to avoid local tissue atrophy and other complications.

Pingyangmycin enhances the antitumor efficacy of anti-PD-1 therapy associated with tumor-infiltrating CD8+ T cell augmentation.

PURPOSE: To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells. METHODS: The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the combination of PYM with anti-PD-1 antibody. The ELISA kits were used to quantify the ICD related ATP and HMGB1 levels. The Transwell assay was conducted to determine the chemotaxis ability of THP-1 cell in vitro. The flow cytometry was used to measure reactive oxygen species level and analyze the ratio of immune cell subsets. RESULTS: PYM induced ICD in murine 4T1 breast cancer and B16 melanoma cells and increased the release of nucleic acid fragments that may further promote the monocytic chemotaxis. In the 4T1 murine breast cancer model, PYM alone, anti-PD-1 antibody alone, and their combination suppressed tumor growth by 66.3%, 16.1% and 77.6%, respectively. PYM markedly enhanced the therapeutic efficacy of anti-PD-1 antibody against 4T1 breast cancer. The calculated CDI (coefficient of drug interaction) indicated synergistic effect. Evaluated by graphic analysis, the nucleated cells intensity in the femur bone marrow remained unchanged. Histopathological observations revealed no noticeable toxico-pathological changes in the lung and various organs, indicating that the PYM and anti-PD-1 antibody combination exerted enhanced efficacy at well-tolerated dosage level. By the combination treatment, a panel of immunological changes emerged. The ratio of CD3+ cells, NK cells and NKT cells increased and Tregs decreased in peripheral blood. The DCs increased in the spleen. Prominent changes occurred in tumor infiltrating lymphocytes. The ratio of CD8+ cells increased, while that of CD4+ cells decreased; however, the ratio of CD3+ cells remained unchanged, implying that certain immunological responses emerged in the tumor microenvironment. PYM alone could also increase CD8+ cells and reduce CD4+ cells in tumor infiltrating lymphocytes. CONCLUSIONS: The studies indicate that PYM, as an ICD inducer with mild myelosuppression effect, may enhance the therapeutic efficacy of anti-PD-1 antibody in association with tumor infiltrating CD8+ T cell augmentation.

Neochlorogenic acid enhances the antitumor effects of pingyangmycin via regulating TOP2A.

Neochlorogenic acid (NCA), a natural compound found in honeysuckle, possesses prominent anti­inflammatory and antitumor effects. Pingyangmycin (PYM) induces DNA damage and has been used for the treatment of oral and maxillofacial tumors. Oral care serves an important role in promoting wound healing during chemotherapy in patients with oral squamous cell carcinoma (OSCC). Therefore, the present study aimed to analyze the effects of NCA and PYM on OSCC cells and to investigate the potential underlying mechanism. Reverse transcription­quantitative PCR and western blotting were conducted to analyze the expression levels of DNA topoisomerase II α (TOP2A) in different OSCC cell lines. TOP2A­overexpression cells were constructed via transfection of TOP2A­overexpression plasmids. Following NCA or PYM treatment, cell proliferation was assessed using Cell Counting Kit­8 and colony formation assays, whereas cell apoptosis and the cell cycle distribution were assessed via TUNEL staining and flow cytometry, respectively. In addition, the expression levels of apoptosis­ and cell cycle­related proteins were detected via western blotting. Moreover, co­immunoprecipitation (Co­IP) was conducted to determine whether TOP2A interacted with CDK1. The results of the present study indicated that NCA treatment significantly enhanced the suppressive effects of PYM on OSCC cell proliferation and apoptosis. The results also indicated that PYM arrested the cell cycle in the G0/1 by regulating cyclin dependent kinase 1 (CDK1)/cyclin B1, which was enhanced by the cotreatment of NCA and PYM. In addition, NCA and PYA treatment altered the expression levels of apoptosis­related proteins. The Co­IP assay indicated that TOP2A interacted with CDK1. Moreover, TOP2A overexpression significantly reversed the effects of NCA and PYM treatment on OSCC cell proliferation and apoptosis. In addition, NCA significantly decreased PYM­induced toxicity in normal oral epithelial cells. In conclusion, the results of the present study suggested that NCA may promote the inhibitory effects of PYM in OSCC via TOP2A.

Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas. MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data. RESULTS: Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was - 4.37( - 5.32, - 3.42), - 4.70( - 5.70, - 3.71), - 0.93( - 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%-100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%). CONCLUSIONS: Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation.

DSA-guided percutaneous sclerotherapy for children with oropharyngeal low-flow venous malformation.

The present study investigated the efficacy and safety of digital subtraction angiography-guided 3% polidocanol foam sclerosing agent, as well as the combination of pingyangmycin and dexamethasone, for the treatment of children with oropharyngeal low-flow venous malformation. A total of 27 children with 35 lesions with oropharyngeal low-flow venous malformation were included. The subjects were randomly divided into Groups A (13 patients with 16 lesions, treated with 3% polidocanol foam sclerosing agent) and B (14 patients with 19 lesions, treated with pingyangmycin + dexamethasone), respectively. The clinical efficacies and adverse reactions were analyzed and compared between these two groups. The average number of treatment times for Group A was 2.45±0.6, with an efficacy rate of 87.50%, while the average number of treatment times for Group B was 2.07±0.4, with an efficacy rate of 84.21%. No significant difference was found in the average treatment times or efficacy rates between Groups A and B. In addition, the adverse reaction incidence for Groups A and B were 38.46 and 14.29%, respectively, with statistically significant differences between these two groups. The combination of pingyangmycin and dexamethasone was safe and effective in treating children with oropharyngeal low-flow venous malformation, with fewer adverse reactions and is worthy of clinical promotion.

Pingyangmycin inhibits glycosaminoglycan sulphation in both cancer cells and tumour tissues.

Pingyangmycin is a clinically used anticancer drug and induces lung fibrosis in certain cancer patients. We previously reported that the negatively charged cell surface glycosaminoglycans are involved in the cellular uptake of the positively charged pingyangmycin. However, it is unknown if pingyangmycin affects glycosaminoglycan structures. Seven cell lines and a Lewis lung carcinoma-injected C57BL/6 mouse model were used to understand the cytotoxicity of pingyangmycin and its effect on glycosaminoglycan biosynthesis. Stable isotope labelling coupled with LC/MS method was used to quantify glycosaminoglycan disaccharide compositions from pingyangmycin-treated and untreated cell and tumour samples. Pingyangmycin reduced both chondroitin sulphate and heparan sulphate sulphation in cancer cells and in tumours. The effect was persistent at different pingyangmycin concentrations and at different exposure times. Moreover, the cytotoxicity of pingyangmycin was decreased in the presence of soluble glycosaminoglycans, in the glycosaminoglycan-deficient cell line CHO745, and in the presence of chlorate. A flow cytometry-based cell surface FGF/FGFR/glycosaminoglycan binding assay also showed that pingyangmycin changed cell surface glycosaminoglycan structures. Changes in the structures of glycosaminoglycans may be related to fibrosis induced by pingyangmycin in certain cancer patients.

Efficacy of propranolol and pingyangmycin, respectively, combined with pulsed dye laser on children with hemangioma.

Clinical efficacy of propranolol and pingyangmycin, respectively, combined with pulsed dye laser in the treatment of children with hemangioma was analyzed, to provide a new therapeutic idea for their clinical treatment. A total of 120 children with hemangioma were selected into the study. Children treated with propranolol combined with pulsed dye laser were in group A, those treated with pingyangmycin combined with pulsed dye laser were in group B, and 60 healthy children were selected as control group (group C). Blood samples of children were taken before and after treatment for miR-4295 detection. The expression of miR-4295 was observed after treatment, and the total clinical remission rate and adverse reactions after treatment were compared between the two groups. The tumor volume of the two groups was significantly reduced after treatment, with statistically significant difference (P<0.05); miR-4295 expression was reduced in the two groups (P<0.05); adverse reactions in propranolol group were less than pingyangmycin group during treatment (P<0.05). Propranolol and pingyangmycin, respectively, combined with pulsed dye laser had ideal efficacy on hemangioma in children. Moreover, miR-4295 was highly expressed in children with hemangioma, and the expression level reduced after two methods of treatment. However, adverse reactions in propranolol group were less and its safety was higher.

An efficient procedure for preparing high-purity pingyangmycin and boanmycin from Streptomyces verticillus var. pingyangensis fermentation broth via macroporous cation-exchange resin and subsequent reversed-phase preparative chromatography.

Pingyangmycin (PYM) and boanmycin (BAM), two individual components of bleomycin (bleomycin A5 and bleomycin A6), are glycopeptide antitumor antibiotics. An efficient procedure for the preparation of PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth using macroporous cation-exchange (MCE) resin followed by medium-pressure preparative liquid chromatography (MPLC) based on monodisperse poly(styrene-co-divinylbenzene) (p(st-dvb)) microspheres was investigated in this paper. Nine frequently used MCE resins were screened by static adsorption and desorption to enrich PYM and BAM fromthe fermentation broth, and D157 resin was found to be the most effective. After one run of column-based dynamic adsorption and desorption, the contents of PYM and BAM were increased by factors of 13.8 and 12.1 with recovery yields of 84.21% and 81.47%, respectively. The enriched samples were subjected to MPLC with columns prepacked with the PolyRP 10-300 microspheres. The operational parameters of the MPLC, including the stationary phase and mobile phase compositions, sample/stationary phase ratio, sample loading scale and flow rate, were screened and optimized. The results showed that the separation and purification for PYM and BAM by MPLC were dramatically improved with a mobile phase modifier of 0.15 mol/L ammonium chloride aqueoussolution, a flow rate of 10 mL/min and a sample/stationary phase ratio of 1.0:100 (m/v, g/mL), and PYM and BAM with purities of more than 98.65% and 99.12% were obtained, respectively. The total recoveries of PYM and BAM reached 75.38% and 70.31%. The separation and purification method is simple, efficient, energy-saving, environmentally friendly and suitable for the large-scale preparation of high-purity PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth.

Urethral cavernous hemangioma: a highly misdiagnosed disease (a case report of two patients and literature review).

BACKGROUND: Diagnosis of urethral cavernous hemangioma (UCH) is very rare. It can be easy to misdiagnose and mistreat due to its atypical clinical manifestations and a lack of relevant knowledge. The study is to explore the diagnosis, differential diagnosis, and treatment of UCH. CASE PRESENTATION: The first patient was a 15-year-old male, who was admitted to the hospital for more than 1 year with repeated hematuria. UCH was diagnosed by cystoscope biopsy, and cured with local injection of pingyangmycin. The second patient was a 49-year-old male, who was admitted for repeated painless gross hematuria and intermittent urethral bleeding after penile erection for more than 20 years. The case had been misdiagnosed as seminal vesiculitis, urethritis, or prostatitis, for over 20 years, until it was diagnosed as UCH by MR examination of the penis. It was treated by injection of pingyangmycin into the hemangioma's lumen and base. A small incision in the ventral penile area was separated from the location of the hemangioma, which was injected with pingyangmycin again. A biopsy of resected tissue further confirmed the diagnosis of UCH. CONCLUSIONS: UCH is an easily misdiagnosed disease. Intermittent painless hematuria is important characteristic of UCH. Local injection of pingyangmycin is a good option for treatment of UCH.

Efficacy and security of lauromacrogol and pingyangmycin in treatment of hemangioma and venous malformation: A meta-analysis / 解放军医学杂志

Objective: To systematically evaluate the clinical efficacy and safety of pingyangmycin and lauromacrogol in treatment of hemangioma or venous malformation. Methods: All the databases of PubMed, Cochrane Library, Embase, Web of Science, Wanfang, CBM, VIP and CNKI were searched from their inception to November 30, 2018 to seek the randomly controlled trials (RCTs) involving the efficacy and adverse reaction of lauromacrogol and pingyangmycin in treatment of hemangioma and venous malformation. According to the inclusion and exclusion criteria, two reviewers were respectively responsible for screening researches, extracting data and assessing the risk of bias of included studies. Subsequently, meta-analysis was performed with RevMan 5.3 software. Results: A total of 12 studies containing 1619 individuals with hemangioma or venous malformation were incorporated. Meta analysis showed that the cured rates of hemangioma and venous malformation were superior when treated with lauromacrogol than with pingyangmycin, the difference was statistically significant (OR=1.98, 95%CI 1.58-2.49, P<0.001). While no significant difference existed in the efficiency (OR=1.17, 95%CI 0.40-3.41, P=0.77) and inefficiency (OR=0.44, 95%CI 0.12-1.66, P=0.23) when treating hemangioma and venous malformation with lauromacrogol or pingyangmycin. The incidence of complication was distinctly lower in lauromacrogol group than in pingyangmycin group with statistical significance (OR=0.27, 95%CI 0.17-0.44, P<0.001). Conclusion: In the treatment of hemangioma and venous malformation, lauromacrogol is obviously superior to pingyangmycin in the therapeutic effect and safety, but there is no significant difference in effectively reducing the focus.

Advances in intralesional injections for infantile hemangioma / 中华整形外科杂志

Intralesional injection is a common method among various therapeutic choices for the treatment of Infantile Hemangiomas. This article reviews the clinical application of intralesional injections for infantile hemangiomas, discusses indications for intralesional injection treatment and evaluates the safety and efficacy of different injected drugs.

Chitosan-based liposomal thermogels for the controlled delivery of pingyangmycin: design, optimization and in vitro and in vivo studies.

Pingyangmycin (PYM) has been applied clinically for many years to treat vascular malformations (VM) in China. The major limitation of PYM injections is quick diffusion from the injection site, which increases side effects, especially the possibility of pulmonary injury. In this paper, chitosan/glycerophosphate disodium (CS/GP) thermogels containing liposomes for sustained and localized PYM delivery were prepared and optimized by a three-level three-factorial Box-Behnken experimental design to evaluate the effects of different variables (the PYM concentration, CS amount and GP content), on the selected responses (cumulative percentage PYM released in 1 day, 9 days and the rate constant k). The results revealed that the optimized PYM liposomal thermogels had a controlled PYM release for 14 days in vitro, which confirmed the validity of optimization. In vitro morphological observation, cell cycle and apoptosis analysis showed an effective anti-proliferation action of PYM liposomal thermogels on human vascular endothelial cells (EA.hy926). In vivo pharmacokinetics research in rabbits displayed that compared with PYM liposomes and PYM thermogels, PYM liposomal thermogels had a better controlled delivery of PYM. Histological examination of rabbit ear veins showed that after local application with PYM lipsomal thermogels for 21 days, obvious vein thrombosis and inflammatory reaction could be observed. The above results indicated that PYM-loaded lipsomal CS/GP thermogels might have a good prospect for the treatment of VM.