Mechanism of LEF1-AS1 regulating HUVEC cells by targeting miR-489-3p/S100A11 axis.

Background: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and S100A11 in HUVEC cells. Methods: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests. Results: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation. Conclusions: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.

MBUTransNet: multi-branch U-shaped network fusion transformer architecture for medical image segmentation.

PURPOSE: Recently, transformers have been adopted to computer vision applications and achieve great success in image segmentation. However by simply applying transformers to medical segmentation task it is hard to achieve much higher accuracy than by traditional U-shaped network structures, which are based on CNNs and has been extensively researched. On the other hand, CNN structure pays more attention to local information and ignores global information, which is very important for the medical image segmentation dataset with cell scattered background. This motivates us to explore the feasibility of using U-shape effective fusion transformer network architectures for medical image segmentation tasks. METHODS: In this paper, we propose a multibranch U-shaped structure fusion transformer network (MBUTransNet), which consists of two distinct branches. In branch 1, Coordinate attention transformer is designed to extract long-term dependency information through weight coordinates. In branch 2, small U-net blocks and multiscale feature fusion block are proposed to replace convolution blocks of each layer and fuse the feature maps from different layers, respectively. RESULTS: Our experiments demonstrate that the proposed MBUTransNet has achieved a 0.076 and 0.1269 improvement in DICE compared to the previous best method on MoNuSeg and Synapse multiorgan segmentation dataset, respectively, while the model parameters will be no significant increase. CONCLUSION: Without bells and whistles, MBUTransNet achieves better performance on medical image datasets, including medical cell segmentation and abdominal organs segmentation. Compared with transformer-based methods, our proposed model also obtains quite competitive parameters.

Efficacy of Combined Topical Timolol and Oral Propranolol for Treating Infantile Hemangioma: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Oral propranolol has become the first-line treatment for infantile hemangioma (IH). However, combined therapy with topical timolol and oral propranolol has been proposed as a more effective IH treatment strategy. We aimed to compare the safety and efficacy of topical timolol, oral propranolol, and their combination for treating IH in a meta-analysis. METHODS: Relevant randomized controlled trials (RCTs) were obtained after searching the PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure, and WanFang databases. A random-effect model was used to pool the results. RESULTS: Eight RCTs with 759 patients with IH were included in this meta-analysis. Treatment with topical timolol alone showed a similar response rate compared to oral propranolol (risk ratio [RR] = 0.97, p = 0.63), but resulted in fewer adverse events (RR = 0.36, p = 0.002). Combined treatment with topical timolol and oral propranolol showed a favorable response rate compared to treatment with oral propranolol (RR = 1.14, p = 0.03) or topical timolol (RR = 1.36, p = 0.01) alone. Moreover, combined treatment showed similar risks of adverse events compared to oral propranolol (RR = 0.80, p = 0.24) or topical timolol (RR = 1.31, p = 0.25) alone. CONCLUSIONS: Combined treatment with topical timolol and oral propranolol may be more effective than either single treatment strategy in patients with IH. Topical timolol alone conferred similar efficacy for IH compared to oral propranolol, but with less incidence of adverse events.

Clinical significance of galectin-3 expression in malformed hepatic venous tissue.

BACKGROUND & OBJECTIVES: Hepatic venous malformation gradually develops over time and exhibits the malignant biological behaviours of being locally invasive, causing morphological and functional damage to local tissue, and may even cause systemic coagulopathy. Studies show that galectin-3(Gal-3) expression is closely associated with local invasion of malignant tumours. In this study an attempt was made to assess the clinical significance of Gal-3 in local invasion during hepatic venous malformation in patients. METHODS: Gal-3 protein and its mRNA expression were examined using immunohistochemistry and in situ hybridization in a total of 126 patients with hepatic venous malformation. For control tissue, 20 cases of normal tissue distal to surgical margins were also examined. In addition, the association between Gal-3 expression and pathological parameters was analyzed in hepatic venous malformation patients. RESULTS: Gal-3 mRNA positivity was observed in 65.08 per cent (82/126) of hepatic venous malformation tissue samples, which was higher than the rate of 20 per cent (4/20) (P <0.05) seen in control tissues. Gal-3 protein positivity was observed in 58.73 per cent (74/126) of hepatic venous malformation tissue samples, which was higher than the rate of 15 per cent (3/20) (P <0.05) seen in the normal tissue. Gal-3 expression was not significantly associated with age or gender. However, there was a significant association between Gal-3 positivity and lesion size, local invasion depth, and involvement with the hepatic vein and the portal system. INTERPRETATION & CONCLUSIONS: Local tissue invasion and destruction by hepatic venous malformation may be related to the upregulation of Gal-3. Gal-3 expression and the development of venous malformation may be related and needs to be studied further.

Pingyangmycin Pretreatment Influences the Biological Behavior of Ocular Venous Malformation and Relates with Galectin-3 Expression.

BACKGROUND: Galectin-3 (Gal-3) plays a role in the mechanisms underlying ocular venous malformation. We conducted this study to investigate the effect of pingyangmycin pretreatment on the Gal-3 expressions and biological behavior of ocular venous malformation. METHODS: Tissue samples were collected from 136 patients with ocular venous malformation. Patients were randomly divided into pingyangmycin (n = 69) and nonpingyangmycin group (n = 67). Patients in the pingyangmycin group received a local injection of 0.02% pingyangmycin once every 2 days for 2 weeks (7 doses) before removal surgery, whereas patients in the nonpingyangmycin group underwent removal surgery without local injection. The protein and messenger RNA (mRNA) expression of Gal-3 were detected by using immunohistochemistry and in situ hybridization. RESULTS: Gal-3 protein was expressed in 35 (52%) of 67 samples in the nonpingyangmycin group and in 19 (28%) of 69 samples in the pingyangmycin group (P < 0.05). Gal-3 mRNA expression was detected in 39 (58%) of 67 samples in the nonpingyangmycin group and 22 (32%) of 69 samples in the pingyangmycin group (P < 0.05). The higher Gal-3 expressions were detected in samples with deeper invasiveness than those with superficial invasiveness before (χ2 = 12.720 and 13.369, respectively, both P < 0.05) and after pingyangmycin treatment (χ2 = 8.429 and 4.590, respectively, both P < 0.05). It was more frequently detected in mesh-like lesions with unclear boundary than round lesions with clear boundary before (χ2 = 30.291 and 41.466, respectively, both P < 0.05) and after pingyangmycin treatment (χ2 = 14.619 and 15.130, respectively, both P < 0.05). Pingyangmycin treatment led to a significant difference in Gal-3 expressions at both protein and mRNA levels (χ2 = 8.664 and 9.524, respectively, both P < 0.05). CONCLUSIONS: Gal-3 expression may be involved in the development and invasiveness of ocular venous malformation, and pingyangmycin can inhibit Gal-3 expression, indicating a role of pingyangmycin treatment before the removal of ocular venous malformation.

[Analysis of the pain in extremities caused by intramuscular venous malformation and surgical treatments].

Objective: To analyze the pain caused by intramuscular venous malformation, so as to avoid misdiagnosis. Methods: We retrospectively analyzed 173 patients who received surgical treatments in our department between Jan.2012 to Dec.2014,with the main complaint of local pain and were diagnosed as intramuscular venous malformation. The mechanisms of the local pain, based on the image data, intra-operative findings, pathology reports and the comparison of the Visual Analogue Scale(VAS)data before and after operation were summarized. The surgical interventions included simple excision or excision + adhesiolysis or excision + adhesiolysis + nerve decompression. Results: The reasons of local pain can be divided into 4 categories:①lesion located in the tendon insertions;②lesion involving the local nerve, inducing the thickening and tensing of its epineurium and the increasing of its diameter;③lesion infiltrated to the periosteum;④phlebolith in it. All the 173 patients received surgical treatments and got varying degrees of relieving from local pain.63 patients got a decrease of the VAS by 5 or more, and 95 cases' VAS number decreased by 3-4,the rest 15 patients' VAS cut down by 1-2. Conclusions: Intramuscular venous malformation is an important reason for local pain and should not be neglected. Surgical treatment can be an effective method to remove the lesion and relieve local pain.

[Management of Kasabach-Merritt syndrome by drug therapy and surgery].

OBJECTIVE: To summarize the characters of Kasabach-Merritt syndrome (KMS) and to evaluate the therapeutic effect of drug therapy combined with surgery. METHODS: From 2004 to 2010, 59 cases with KMS, who underwent drug therapy and surgery, were retrospectively studied. The average age of the patients, including 33 male and 26 female (male/female, 1.269/1), was 2.9 months (range, 7 days-2.5 years). 28 cases with maxillofacial lesions were treated with the ligation of external carotid artery and injection of carbonyldiamide and methylprednisolone. 31 cases with lesions at trunks and extremities were treated by excision of lesions. All the patients were followed up for 2.8 years (range, 6.5 months -7.3 years). Therapeutic outcomes were assessed by evaluating platelet counts,size of lesion, function of trunk and limb. RESULTS: 58 cases were cured except for one dead case. Emergency operation was given in 4 cases, and selective operation was performed in other cases (55 cases). The thrombocyte count, hemoglobin and blood coagulation function returned to normal within 1-2 weeks. The mental condition, appetite, body weight,sleeping were greatly improved one week after treatment. The size of the lesions decreased gradually after the management of ligation of external carotid artery including 18 cases within 6-12 months and 10 cases within 13-24 months. Long term follow-up studies indicated that there was no recurrent case, and the weight, height, immunity of the patients with good function activities were in keeping with the normal counterparts. CONCLUSIONS: The drug combined with surgery therapy is a very reliable management with high curative rate, short disease period and minimum side-effect.

[Combined treatment with urea injection and surgical procedure for the scrotal vein malformation in teenagers].

OBJECTIVE: To discuss the treatment of the scrotal vein malformation in teenagers and clinical efficacy. METHODS: 32 cases with the local and diffuse scrotal vein malformation were retrospectively analyzed. 31 cases underwent local injection with 40% urea before resection. The urea was injected locally into tumor through multi-points within 30 seconds, 2-6 ml every time, one time a day. The injection was performed for 5-12 days. The treatment was refused in one case. The therapeutic effect and cosmetic result were recorded. RESULTS: The tumors were removed radically in 28 cases including one operation in 25 cases and secondary operation in 3 cases. The patients were followed up for 1-3 years with no recurrence. Cosmetic result with bilaterally symmetric scrotum was satisfactory. The tumors in 3 severe cases were partially resected with improvement. CONCLUSIONS: Combined treatment with urea injection and surgical procedure can effectively treat the scrotal vein malformation with satisfactory result.

[Combined and sequential therapy for Kasabach-Merritt syndrome].

OBJECTIVE: To review and summarize the clinical characteristics and therapeutic approaches of Kasabach-Merritt syndrome (KMS). METHODS: The combined and sequential therapy was used to for 51 KMS infants between 2005 and 2009. And all cases were retrospectively analyzed. There were 27 males and 24 females with a median age of 1.8 months (range: 2 days to 2.5 years). Among them, lesions were located in maxillofacial (n = 20), truck (n = 4), upper extremities (n = 11) and lower extremities (n = 16). RESULTS: Among them, 47 of 51 patients were cured, 3 cases were effectively treated and only 1 patient died of multiple organ failure post-operation. Of the 51 cases, emergency surgery was given in 3 cases while other 48 cases were initially treated with methylprednisolone. The responses were varied: excellent and rapid improvement (n = 12); moderate response (n = 15) and total failure (n = 21). Immunoglobulin was used a second-line therapy for those (n = 21) unresponsive to steroid, with sensitive response (n = 5), effective response (n = 7) and invalid response (n = 9) respectively. And adjunct carbonyldiamide therapy was combined. Conservative treatment was tried in 14 patients. Then 11 curative cases and 3 effective cases were observed. The thrombocyte count in 4 cases returned to normal within 4 - 7 days, 5 cases within 8 - 14 days, and 2 cases within 15 - 28 days. In the remaining 3 cases, it normalized more than 28 days. The hemangiomas in 6 cases disappeared completely in 6 - 12 months and 8 cases disappeared in 13 - 24 months. 19 patients were treated with the ligation of external carotid artery, the insertion of a tube inside the lesion and the injections of carbonyldiamide and methylprednisolone. The platelet counts of 13 cases increased to normal in 4 - 7 days of the treatment, and 6 cases in 8 - 14 days. The tumors of 12 cases disappeared within 6 - 12 months, and 7 cases within 13 - 24 months. Combined surgical resection including emergency operation (n = 3) and selective operation (n = 15) was performed in 18 patients. And all cases except for one were cured. The platelet counts of that the hemangiomas of 10 cases were excised surgically completely increased rapidly and reached the normal range in post-operative 1 - 3 days. The counts of 8 cases after subtotal resection increased to normal within 8-14 days. CONCLUSION: A stepwise multimodal approach is recommended for the treatment of KMS. With a higher curative rate, it has minimal side effects.