Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound A16 showed potent kinase activity comparable to that of AZD4547. In addition, A16 effectively suppressed the activation of lung fibroblasts and hepatic stellate cells (HSCs) induced by TGF-β1, leading to a reduction in collagen deposition. Notably, A16 exhibited potent anti-fibrotic effects through the inhibition of the FGFR pathway in vitro. Compound A16 also showed reasonable pharmacokinetic properties (F = 21.84 %) and favorable cardiac safety (hERG IC50 > 20 μM). Moreover, in models of pulmonary fibrosis, A16 ameliorated (in the prevention model) and reversed (in the treatment model) bleomycin-induced lung fibrosis, as well as mitigated inflammatory immune response in the lung. Furthermore, in the CCl4-induced liver fibrosis model, when A16 was administrated orally at a dose of 30 mg/kg/day for 3 weeks, it effectively improved liver function, restored damaged liver structures, and reduced collagen deposition. Taken together, these results suggest that A16 could be a potential drug candidate for the treatment of organ fibrosis.

目的 探讨在猪股动脉球囊血管成形术中,微针球囊注射紫杉醇到股动脉鞘的安全性与有效性.方法 10只巴马香猪随机抽样分成3组,其中对照组与实验组各4只,选取单侧股动脉;空白对照组2只,选取双侧股动脉.在数字减影血管造影(DSA)造影下选取直径约4 mm的股动脉作为靶血管,予以扩张至6 mm达到血管损伤的目的.实验组应用微针球囊注射1 ml紫杉醇显影剂复合物到动脉鞘;对照组应用药物涂层球囊(DCB)释放紫杉醇涂层到血管内膜;空白对照组应用微针球囊注射1ml生理盐水到动脉鞘.实验组与对照组分别于术后1 h、48 h、7 d、14 d检测紫杉醇血药浓度,在术后60 d检测靶血管段的紫杉醇含量;术后60 d 3组靶血管均行苏木精-伊红(HE)染色,在镜下测量相关数据并应用SPSS 20.0进行统计分析.结果 实验组中紫杉醇血药浓度高于对照组,配对样本 Wilcoxon 秩和检验结果为 0.068(0.010,0.092)、0.068(0.005,0.092)(Z=2.12,P＜0.05).血管狭窄率的比较中,对照组与实验组相当,均优于空白对照组,方差分析结果为(42±6)％、(46±8)％、(52±7)％(F=3.87,P＜0.05),LSD法进行组间两两比较,对照组与空白对照组有统计学差异,其余组间差异无统计学意义.管腔面积/外膜面积比的比较中,实验组与对照组相当,均优于空白对照组,方差分析结果为(35±9)％、(33±7)％、(23±7)％(F=6.21,P＜0.05),LSD法进行两两比较,实验组与空白对照组、对照组与空白对照组均有统计学差异,实验组与对照组差异无统计学意义.结论 微针球囊注射紫杉醇到股动脉鞘是安全的,可以产生与DCB相同的防治动脉狭窄的效果,为ASO的腔内治疗提供了更多的选择.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix components and results from chronic liver injury. At present, there is no approved drug for the treatment of liver fibrosis by the Food and Drug Administration. Here, we have reported a series of novel compounds with phenacrylanilide scaffolds that potently inhibit the transfer growth factor β1 (TGF-β1)-induced activation of LX-2, a hepatic stellate cell (HSC) line. Among them, compound 42 suppressed TGF-β1-induced upregulation of fibrotic markers (α-SMA and fibronectin) and showed excellent safety in vitro. Furthermore, in a carbon tetrachloride (CCl4) -induced liver fibrosis model, 42 at a dose of 30 mg/kg/day through oral administration for 3 weeks effectively improved liver function, restored damaged liver structures, and reduced collagen deposition, with a greater effect than Tranilast. In addition, epithelial-mesenchymal transition (EMT) is inhibited by compound 42 in the process of fibrosis. Meanwhile, the imbalanced immune microenvironment could also be effectively reversed. More interestingly, compound 42 prolongs the survival of CCl4 mice and ameliorates CCl4-induced injury to spleen, kidney, lung and heart. Altogether, these results suggest that 42 could be a potential drug candidate for the treatment of liver fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF), a life-threatening interstitial lung disease, is characterized by excessive activation and proliferation of fibroblasts and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) accompanied by a large amount of extracellular matrix aggregation. There are no therapies to reverse pulmonary fibrosis, and nintedanib and pirfenidone could only slow down the decline of lung function of IPF patients and delay their survival time. Niclosamide (Ncl) is an antihelminthic drug approved by FDA, which has been reported to have pleiotropic pharmacological activities in recent years, but it's almost complete insolubility in water limits its clinical application.Objectives: To improve the water solubility of Ncl, explore its ability to reverse BLM-induced pulmonary fibrosis and its specific mechanism of action.Methods: The Niclosamide-loaded nanoparticles (Ncl-NPs) were formed by emulsification solvent evaporation method. A mouse model induced by bleomycin (BLM) was established to evaluate its effects and mechanisms of inhibiting and reversing fibrosis in vivo. The cell models treated by transforming growth factor-b1 (TGF-b1) were used to examine the mechanism of Ncl-NPs inhibiting fibrosis in vitro. Flow cytometry, IHC, IL-4-induced macrophage model and co-culture system were used to assess the effect of Ncl-NPs on M2 polarization of macrophages.Results: The Ncl-NPs improved the poor water solubility of Ncl. The lower dose of Ncl-NPs (2.5 mg/kg) showed the same effect of reversing established pulmonary fibrosis as free Ncl (5 mg/kg). Mechanistic studies revealed that Ncl-NPs blocked TGF-0/Smad and signaling transducer and activator of transcription 3 (Stat3) signaling pathways and inhibited the M2 polarization of macrophages. Additionally, H & E staining of the tissues initially showed the safety of Ncl-NPs.Conclusion: These results indicate Ncl-NPs may serve as a new idea for the treatment of pulmonary fibrosis.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease with a complex pathogenesis and high mortality. The development of new drugs is time-consuming and laborious; therefore, research on the new use of old drugs can save time and clinical costs and even avoid serious side effects. Nifuroxazide (NIF) was originally used to treat diarrhoea, but more recently, it has been found to have additional pharmacological effects, such as anti-tumour effects and inhibition of inflammatory diseases related to diabetic nephropathy. However, there are no reports regarding its role in pulmonary fibrosis. The therapeutic effect of NIF on pulmonary fibrosis in vivo was measured by ELISA, hydroxyproline content, H&E and Masson staining, immunohistochemistry (IHC) and western blot. Immune cell content in lung tissue was also analysed by flow cytometry. NIF cytotoxicity was evaluated in NIH/3T3 cells, human pulmonary fibroblasts (HPFs), A549 cells and rat primary lung fibroblasts (RPLFs) using the MTT assay. Finally, an in vitro cell model created by transforming growth factor-β1 (TGF-β1) stimulation was assessed using different experiments (immunofluorescence, western blot and wound migration assay) to evaluate the effects of NIF on the activation of NIH/3T3 and HPF cells and the epithelial-mesenchymal transition (EMT) and migration of A549 cells. In vivo, intraperitoneal injection of NIF relieved and reversed pulmonary fibrosis caused by bleomycin (BLM) bronchial instillation. In addition, NIF inhibited the expression of a variety of cellular inflammatory factors and immune cells. Furthermore, NIF suppressed the activation of fibroblasts and EMT of epithelial cells induced by TGF-β1. Most importantly, we used an analytical docking experiment and thermal shift assay to further verify that NIF functions in conjunction with signal transducer and activator of transcription 3 (Stat3). Moreover, NIF inhibited the TGF-β/Smad pathway in vitro and decreased the expression of phosphorylated Stat3 in vitro and in vivo. Taken together, we conclude that NIF inhibits and reverses pulmonary fibrosis, and these results support NIF as a viable therapeutic option for IPF treatment.

Liver fibrosis is an abnormal wound repair response caused by a variety of chronic liver injuries, which is characterized by over-deposition of diffuse extracellular matrix (ECM) and anomalous hyperplasia of connective tissue, and it may further develop into liver cirrhosis, liver failure or liver cancer. To date, chronic liver diseases accompanied with liver fibrosis have caused significant morbidity and mortality in the world with increasing tendency. Although early liver fibrosis has been reported to be reversible, the detailed mechanism of reversing liver fibrosis is still unclear and there is lack of an effective treatment for liver fibrosis. Thus, it is still a top priority for the research and development of anti-fibrosis drugs. In recent years, many strategies have emerged as crucial means to inhibit the occurrence and development of liver fibrosis including anti-inflammation and liver protection, inhibition of hepatic stellate cells (HSCs) activation and proliferation, reduction of ECM overproduction and acceleration of ECM degradation. Moreover, gene therapy has been proved to be a promising anti-fibrosis method. Here, we provide an overview of the relevant targets and drugs under development. We aim to classify and summarize their potential roles in treatment of liver fibrosis, and discuss the challenges and development of anti-fibrosis drugs.

Fibrosis, a common process of chronic inflammatory diseases, is defined as a repair response disorder when organs undergo continuous damage, ultimately leading to scar formation and functional failure. Around the world, fibrotic diseases cause high mortality, unfortunately, with limited treatment means in clinical practice. With the development and application of deep sequencing technology, comprehensively exploring the epigenetic mechanism in fibrosis has been allowed. Extensive remodeling of epigenetics controlling various cells phenotype and molecular mechanisms involved in fibrogenesis was subsequently verified. In this review, we summarize the regulatory mechanisms of DNA methylation, histone modification, noncoding RNAs (ncRNAs) and N6-methyladenosine (m6A) modification in organ fibrosis, focusing on heart, liver, lung and kidney. Additionally, we emphasize the diversity of epigenetics in the cellular and molecular mechanisms related to fibrosis. Finally, the potential and prospect of targeted therapy for fibrosis based on epigenetic is discussed.

BACKGROUND:Hemangiopericytomas are rare tumors derived from pericytes surrounding the blood vessels. The clinicopathological characteristics and prognosis of hemangiopericytoma patients remain mostly unknown. In this retrospective cohort study, we assessed the clinicopathological characteristics of hemangiopericytoma patients, as well as the clinical usefulness of different treatment modalities. Material and Methods. We collected the clinicopathological data (between 1975 and 2016) of hemangiopericytoma and hemangioendothelioma patients from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence, treatment, and patient prognosis were assessed.RESULTS:Data from 1474 patients were analyzed in our study cohort (hemangiopericytoma: n = 1243; hemangioendothelioma: n = 231). The incidence of hemangiopericytoma in 2016 was 0.060 per 100,000 individuals. The overall survival (OS) and cancer-specific survival (CSS) did not differ between patients with hemangioendothelioma and those with hemangiopericytoma (P = 0.721, P = 0.544). The tumor grade had no effect on the OS of hemangiopericytoma patients. Multivariate analysis revealed the clinical usefulness of surgery in hemangiopericytoma patients (HR = 0.15, 95% confidence interval: 0.05-0.41, P < 0.001). In contrast, radiotherapy did not improve OS (P = 0.497) or CSS (P = 0.584), and chemotherapy worsened patient survival (P < 0.001). Additionally, the combination of surgery and radiotherapy had a similar effect with surgery alone on hemangiopericytoma patient survival (OS: P = 0.900; CSS: P = 0.156). Surgery plus chemotherapy provided a worse clinical benefit than surgery alone (P < 0.001).CONCLUSIONS:Our findings suggested that hemangiopericytoma had a similar prognosis with hemangioendothelioma. Surgery was the only effective treatment that provided survival benefits in hemangiopericytoma patients, while the clinical usefulness of adjuvant chemotherapy or radiotherapy was limited.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial pneumonia that causes pulmonary tissue damage and functional impairment. To investigate the effects of cryptotanshinone on pulmonary fibrosis, the expression of NIH/3T3, HPF, and rat primary pulmonary fibroblasts was measured and found to be inhibited by CPT in a time‐ and concentration‐dependent manner, and the upregulation of α‐SMA expression in NIH/3T3 and HPF cells, which had been stimulated by TGFβ‐1, was decreased after CPT administration. We observed that CPT could reverse the increase in α‐SMA expression and vimentin and the decrease in E‐cad expression in A549 cells, which had been induced by 5 ng/mL TGFβ‐1, indicating that CPT has inhibitory effects in the EMT process. A BLM‐induced pulmonary fibrosis model was established in C57BL/6 mice. The lung coefficient and hydroxyproline content increased significantly in the BLM‐induced group and were decreased in the CPT‐treated group. The expression levels of collagen‐I and α‐SMA and the phosphorylation level of Stat3 were significantly increased, and CPT treatment decreased these levels. Furthermore, the results from the flow cytometry analysis indicated that, in lung tissues, the frequencies of MDSCs, macrophages, DCs and T cells were considerably increased in the BLM‐induced group, while CPT treatment reduced these immunocyte populations.

Erbin has been shown to maintain the integrity of cell structure, regulate the proliferation and differentiation of cell and transconduct signals in the pathways. This study was conducted to assess the therapeutic effects of an Erbin inhibitor on spinal cord contusion in mice. Spinal contusion models of mouse were constructed and treated with an Erbin inhibitor. The experimental animals were divided into control (normal animal without any treatment), models with spinal cord injury (SIM), and models receiving Erbin inhibitor (Inhibitor). The contents of 5-hydroxytryptamine (5-HT) and reactive oxygen species (ROS) in the brain and spinal cord tissues were measured using ELISA. The expression of ERK1/2, MAPK, NF-kB and NRG1 was quantified using qRT-PCR, Western blot analysis and immunohistochemistry. Flow cytometry was used to determine the formation of macrophages. Erbin interference vector was constructed and its interference effect on the expression of these genes was characterized in cultured bone marrow cells. Spinal contusion models were successfully constructed. Administering Erbin inhibitor inhibited the expression of ERK1/2, MAPK and NF-kB and up-regulated the expression of NRG1. Flow cytometry showed that Erbin inhibitor induced the formation of a large number of macrophages, which are beneficial to the recovery of spinal cord injury. Experiments with Erbin interference vector showed similar impacts on the expression of genes at cellular level as the inhibitor did. Our work has demonstrated that the Erbin inhibitor is very effective to treat spinal cord contusion in mice. The possible mechanism of therapeutic effect is that the inhibitor suppresses the ERK1/2/MAPK and/or NF-kB/MAPK signal pathways and enhances the NRG1-ErbB signaling pathway by reducing the expression of Erbin, leading to the inhibition of apoptosis, promotion of proliferation and differentiation, and subsequent repair of the damaged spinal cord.

目的 比较泡沫硬化剂不同方式治疗下肢静脉曲张的适应征、并发症.方法 根据下肢静脉曲张的病情,选择:①单纯性泡沫硬化疗法,包括顺行和逆行;②彩超监视下泡沫硬化疗法;③大隐静脉高位结扎、EVLT术后泡沫硬化疗法;④CO2气体的泡沫硬化治疗等治疗,观察其并发症和疗效.结果 第①种方式对下肢静脉曲张较细小尤其是小腿部静脉曲张较为适合,由于治疗病例较多,各种并发症也产生较多,但都是一过性或为可逆的;第②种方式治疗下肢静脉曲张较安全,并发症相对较少,但操作上较繁琐,不适于门诊大量病人治疗;第③种方式适用于粗大的大隐静脉主干曲张和有交通支瓣膜关闭不全者;第④种方式产生的并发症最少,尤其是肺动脉气栓的可能性最小,安全性较高.结论 各种方式的泡沫硬化剂治疗下肢静脉曲张均可达到治疗目的,但其安全性不同,并发症产生的机率不同,操作的繁琐程度不同,应根据具体情况作出相应选择.

Objective:To evaluate the potentiality of the recombined adeno-associated virus-2(adeno-associated virus,AAV-2) carrying the human vascular endothelial growth factor-165(vascular endothelial growth factor,VEGF165) and angiopoietin-1(angiopoietin-1) gene in promoting vascular regeneration, by direct injection into muscle tissue of the male New Zealand rabbits.Method:32 male New Zealand white rabbits were randomly divided into four groups,8 rabbits in each group.The virus vector carrying human VEGF165 gene AAV-2-hVEGF165, carrying the human Ang1 gene AAV-2-hAng1,carrying beta-galactosidase(Gal) gene rAAV-2-LacZZ and carrying both human Ang1 and VEGF165 gene AAV-2-hAng1/VEGF165,which directly injected into muscle tissue of the male New Zealand rabbit, vascular regeneration were analyzed by visual observation and immunohistochemical assay 4 weeks later.Result:The muscle tissue injected AAV-2/hAng1/VEGF165 presented rich density and wider diameter of regenerated vascular,which was better than the AAV-2-hVEGF165,AAV-2-hAng1,AAV-2-LacZ in promoting vascular regeneration.Conclusion:Efficient expression and extraordinary vascular regeneration of AAV-2 carrying both human Ang1 and VEGF165 gene is obversed in the muscle tissue, AAV-2-hAng1/VEGF165 not only promote the angiogenesis,arteriogenesis and restoration of blood flow of ischemic limb,but also reduce the permeability of blood vessels,the therapeutic effectiveness is best among other groups.

Objective To explore the relationship between recurrence rate and side effects of the treatment of varicose veins in lower extremity with lauromacrogol foam sclerosing agent.Methods The data of 62 patients(98 limbs)with varicose veins was collected,including 27 males (41 limbs)and 35 females (57 limbs).They were treated with 1％ lauromacrogol foam sclerosing agent combined with great saphenous vein high ligation and endovenous laser treatment.Statistical indicators included side effects such as pain,induration,hyperpigmentation,swelling,numbness and the recurrence rate.Results Two patients were lost,57 patients were injected once,further foam sclerotherapy was carried out again for 3 patients.Obvious abnormal varicose veins as well as the soreness and fatigue of lower extremity disappeared in all patients.Thirty-seven patients had pain and 43 patients developed superficial venous thrombotic sclerosis,among which 50 patients faded away after 1 to 3 months by taking diosmin.Thirty-one cases of pigmentation occurred and 20 disappeared after 1 to 3 months by applying the vitamin E whitening essence.Six patients with lower extremity ulcers recovered after 1 to 3 months.Through statistics analysis of the patients in 1-month follow-up,we found that the differences in recurrence rate after 6 months were statistically significant between group with pain induration reaction and group without (P ＜ 0.05).Among the patients without using the vitamin E whitening essence,there was a significant correlation between the duration of pigmentation and recurrence rate after 6 months.Conclusion In the process of foam sclerotherapy,the more pain induration reaction they had and the longer the duration of pigmentation sustained,the lower the recurrence rate would be accordingly.

Objective:To compare the effectiveness of two treatments of endovenous laser treatment (EVLT) combined with foam sclerotherapy for varicose veins of the lower limbs.Methods:From April 2015 to April 2016,120 patients with varicose veins in our hospital were randomly divided into two groups.Firstly,all patients were given high saphenous vein ligation.Then,60 patients (Group A) were treated with EVLT (trunk) plus foam sclerotherapy(branch and varicose vein group),while another 60 patients (Group B) were treated with EVLT (trunk,branch and large varicose veins) plus foam sclerotherapy(residual varicose veins).The status of perioperative period,the postoperative complication rate and the recurrence rate were compared between the two groups.The venous clinical severity score was also evaluated before operation and after half-oneyear operation.Results:The operative time,cost of hospitalization incidence of pain,skin burn,skin bleeding and limb numbness were higher in group B than those in group A after operation(P＜0.05).No statistically significant difference in perioperative bleeding,postoperative time of out of bed,hospital stay,incidence of thrombophlebitis superficial phlebitis and postopertive recurrence rate between the two groups(P＞0.05).Six months after the operation the venous clinical severity score decreased in both groups (P＜0.05),and there were no significant differences between them(P＜0.05).Conclusion:High saphenous vein ligation plus EVLT(trunk) with foam sclerotherapy(branch and varicose vein group) is worth clinical application for lower extremity varicosity due to its advantages of shorter operative time,fewer complications,better effects,and affordability.

BACKGROUND:Recent findings have elucidated that netrin-1 has ability of promoting angiogenesis besides the functions in nervous system. Autologous mesenchymal stem cells (MSCs) transplantation is now proved to be an effective method to treat peripheral arterial disease. However there are still many patients who cannot complete full treatments. Therefore it is necessary to improve the effectiveness. This study estimated the curative effects in chronic limb ischemia when MSCs allied with netrin-1. MATERIALS AND METHODS:Thirty-six rats were made into chronic limb ischemia models. They were randomly assigned to four groups, netrin-1 + MSCs group (treated with netrin-1 and MSCs derived from peripheral blood), MSCs group (treated with MSCs individually), netrin-1 group (treated with netrin-1 individually), and control group (treated with saline). Measurements of murine behaviors, vascular endothelial growth factor expression, and capillary density in ischemia limb were performed on days 7, 14, and 28 after treatments; measurements of contraction force in ischemia limb was performed on day 28 after treatments to compare differences among the groups. RESULTS:Netrin-1 allied with MSCs significantly increased Tarlov score, vascular endothelial growth factor expression, capillary density, and muscular strength in ischemia limb. CONCLUSIONS:Netrin-1 allied with MSCs derived from peripheral blood significantly promoted angiogenesis in aged rats with chronic limb ischemia. It may be a promising method of treating peripheral arterial disease in the future.

Objective To compare the short-term efficacy of endovenous laser treatment (EVLT) between using 1470nm(Output power 6W)and 810nm(Output power 8W)diode laser for lower extremity varicosity.Methods The data of 30 patients with varicose veins treated by EVLT with the 1470nm diode laser (research group)and 29 patients with varicose veins by EVLT with the 810nm diode laser(control group)were reviewed and compared in terms of operation success rate,operation time, postoperative pain, postoperative hospitalized duration and operative complications.Results The differences between preoperative and postoperative(3-day and 3-month after operation) venous clinical severity score(VCSS)were statistically significant in both groups(P<0.01). The operation success rate ,operation time, postoperative pain, postoperative hospitalized duration, operative complications had no statistical differences between the two groups(P>0.05).Conclusion The 1470nm wavelength and output power 6W EVLT is a treatment for lower extremity varicosity with advantages of safety,effectiveness, energy saving and minimal invasion.

The aim of this study was to construct a plasmid expressing glycoprotein IIb-IIIa (GPIIb/IIIa) and D-dimer single-chain bispecific antibody for the targeted therapy of thrombosis. The phosphorylated gene encoding the anti-GPIIb/IIIa single-chain variable fragment (scFv) and the gene encoding the anti-D-dimer scFv were amplified by PCR and linked in tandem by blunt-end ligation. The recombinant plasmid was transfected into the competent cell line HB2151 and identified by PCR and DNA sequencing. Then, the soluble recombinant antibody in bacterial lysates was purified by an NTA column and molecular sieve chromatography in turn. Finally, the binding specificity of the purified antibody was tested by enzyme-linked immunosorbent assay (ELISA). Results demonstrated that the construction of the expression plasmid was successful and the purified recombinant protein, which had a molecular weight of ∼56 kDa, was specific to GPIIb/IIIa and D-dimer. In conclusion, a plasmid expressing a bispecific antibody was constructed by a new method of blunt-end ligation. The soluble recombinant protein is a promising platform for target-oriented thrombolytic therapy.

<正>静脉畸形肥大综合征是一种罕见的先天异常,由三个体征组成,即血管染色、软组织和(或)骨骼增生、静脉曲张。在现有的影像检查中,CT静脉造影(CTV)能够完整地评价该综合征的病人,不仅能够诊断而且能够用于制定适当的治疗计划。于此基础上,在彩超引导下用聚多卡醇微泡沫注射硬化治疗被认为是先天性静脉畸形骨

目的:系统回顾和Meta分析超声引导下泡沫硬化治疗(UGFS)、腔内激光消融(EVLA)、射频消融(RFA)和传统外科手术(CS)治疗下肢静脉曲张的疗效和复发率.方法:计算机检索Pubmed、Embase、Ovid Med-line和Cochrane Central,收集2000年1月至2012年12月间采用UGFS、EVLA、RFA和CS治疗下肢静脉曲张的随机对照试验(RCT),用统一的风险率(RR)和置信区间(CI)指代不同疗效,按Cochrane协作网推荐的方法进行系统评价.结果:筛选出符合纳入标准22篇文献共25个RCTs,涉及患肢3 497条.分析的结果表明,UGFS和RFA与CS相比干预失败的风险率RR分别是3.42和1.32,而EVLA干预失败的可能性是CS的88％,此结果不具有统计学特异性.腔内介入比CS表现出更低的复发风险RR=0.70 (EVLA),和更低并发症风险[皮下淤血:RR＝0.52(EVLA)和RR=0.13(RFA),感染:RR＝0.35 (EVLA)和RR=0.36 (RFA),感觉异常RR=0.69 (EVLA)].结论:现有证据不能证明UGFS、EVLA和RFA与传统外科手术相比,对治疗下肢静脉曲张的有效率和复发率差异存在统计学特异性,但EVLA和RFA并发症发病风险相对更低.

Neuregulin 1 (NRG1) is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ErbB2 and ErbB3. Recent studies suggest that NRG1 signaling plays a role in remyelination of regenerated nerves after injury. In this study, we investigated the role of Erbin, a protein that interacts with ErbB2 in remyelination of injured nerves. We show that Erbin expression increased dramatically in injured nerves. Myelinated axons were fewer, and g -ratios of those that were myelinated were increased in erbin −/− mice, which were impaired in functional recovery from nerve injury. These results indicate a necessary role of Erbin in remyelination of regenerating axons. Erbin ablation had little effect on numbers of BrdU-labeled and TUNEL-labeled SCs, suggesting mechanisms independent of altered proliferation or apoptosis. We demonstrated that Erbin mutant mice were impaired in raising or maintaining the levels of ErbB2 and in producing NRG1 in axons. Together, these observations demonstrate that Erbin is required for remyelination of regenerated axons after injury, probably by regulating ErbB2 and NRG1 levels, identifying a novel player in regulating remyelination.