Sciatic nerve regeneration using a nerve growth factor-containing fibrin glue membrane

Our previous findings confirmed that the nerve growth factor-containing fibrin glue membrane provides a good microenvironment for peripheral nerve regeneration; however, the precise mechanism remains unclear, p75 neurotrophin receptor （p75NTR） plays an important role in the regulation of peripheral nerve regeneration. We hypothesized that a nerve growth factor-containing fibrin glue membrane can promote neural regeneration by up-regulating p75NTR expression. In this study, we used a silicon nerve conduit to bridge a 15 mm-long sciatic nerve defect and injected a mixture of nerve growth factor and fibrin glue at the anastomotic site of the nerve conduit and the sciatic nerve. Through RT-PCR and western blot analysis, nerve growth factor-containing fibrin glue membrane significantly increased p75NTR mRNA and protein expression in the Schwann cells at the anastomotic site, in particular at 8 weeks after injection of the nerve growth factor/fibrin glue mixture. These results indicate that nerve growth factor-containing fibrin glue membrane can promote peripheral nerve regeneration by up-regulating p75NTR expression in Schwann cells.

Tulip bundle technique and fibrin glue injection:Unusual treatment of colonic perforation

We report a case of a 63-year-old male who experienced an iatrogenic sigmoid perforation repaired combining three endoscopic techniques.The lesion was large and irregular with three discrete perforations,therefore,we decided to close it by placing one clip per perforation,and then connecting all the clips with two endoloops.Finally we chose to use a fibrin glue injection to obtain a complete sealing.Four days after the colonoscopy the patient underwent a laparoscopic right hemicolectomy due to evidence of a large polyp of the caecum with high grade dysplasia and focal carcinoma in situ.Inspection of the sigma showed complete repair of the perforation.This report underlines how a conservative approach,together with a combination of various endoscopic techniques,can resolve complicated iatrogenic perforations of the colon.

A Heterologous Fibrin Glue Enhances the Closure Effect of Surgical Suture on the Repair of Annulus Fibrous Defect in a Sheep Model

Improving the closure effect of surgical suture for repair of annulus fibrosus defects remains an unsolved problem.A new type of porcine fibrin glue was reported for the repair of annulus fibrous defects in sheep models in this study.Continuous axial loading test showed that this glue could effectively improve the closure effect of surgical suture for annulus fibrous defect.Magnetic resonance imaging (MRI) of the lumbar spine confirmed that,compared with nonfibrin glue treated intervertebral discs,it contributed to preservation of the nucleus pulposus and maintained the physiological hydration of the intervertebral discs.Moreover,histomorphology evaluation showed that the porcine fibrin glue could partially reverse degeneration of the injured intervertebral discs.Taken together,porcine fibrin glue can effectively enhance the closure effect of surgical suture on annulus fibrosus,improve the repair effect and slow down the degeneration of the intervertebral disc,and provide a potential therapeutic strategy for degenerative intervertebral disc disease.

Treatment of corneal dermoid with lenticules from small incision lenticule extraction surgery:a surgery assisted by fibrin glue

AIM:To observe the clinical efficacy of the combined use of small incision lenticule extraction(SMILE)-derived lenticule patches in corneal dermoid excision,with fixation of the lenticule patches assisted by fibrin glue.METHODS:Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation.All lenticule patches were fixed by fibrin glue.Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography.The best-corrected visual acuity(BCVA)and ocular dioptric variations were examined preoperatively and postoperatively.Intraocular pressure(IOP)was also monitored in all visited time.RESULTS:Totally,18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients.The mean follow-up time was 11.47±5.28mo.All lenticule patches we resuccessfullyg lued,kept on its location and maintained transparent during the follow-up time,with a consecutive epithelial cover for 1wk.Nine of the patients could coordinate visual and optometry exam well.Their preoperative BCVA is 0.60±0.35 in decimal,significantly improved to 0.80±0.26 in decimal at 6mo postoperatively(Z=-2.392,P=0.017),but the changes of their corneal astigmatism diopters showed no significance,with 2.22±1.91 D preoperatively,and 2.28±1.31 D at 6mo postoperatively(Z=-0.135,P=0.893).Limbal pannus formation occurred in 4(23.52%)cases and decreased with the application of tacrolimus eyedrops.IOP increased in 2(11.76%)cases,but well decreased by timolol maleate eyedrops.All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement.CONCLUSION:Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

Common bile duct injury by fibrin glue: Report of a rare complication

Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications.We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a history of failed laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic bleeding.In view of thepersistent liver dysfunction, xanthochromia and skin itching, the patient was admitted to us for further management.Ultrasound, computed tomography, and magnetic resonance cholangiopancreatography(MRCP) revealed multiple stones in the common bile duct, and liver function tests confirmed the presence of obstructive jaundice and liver damage.Endoscopic retrograde cholangiopancreatography was unsuccessfully performed to remove choledocholithiasis, but a small amount of tissue was removed and pathologically confirmed as calcified biliary mucosa.This was followed by open surgery for suspicious cholangiocarcinoma.There was no evidence of cholangiocarcinoma, but the common bile duct wall had a defect of 8 mm × 10 mm at Calot's triangle.A hard, grid-like foreign body was removed, which proved to be solid fibrin glue.Subsequently, the residual choledocholithiasis was removed by a choledochoscopic procedure, and the common bile duct deletion was repaired by liver round ligament with T-tube drainage.Six months later, endoscopy was performed through the T-tube fistula and showed a well-repaired bile duct wall.Eight months later, MRCP confirmed no bile duct stenosis.A review of reported cases showed that fibrin glue is widely used in surgery, but it can also cause organ damage.Its mechanism may be related to discharge reactions.

Sealing of the hepatic resection area using fibrin glue reduces significant amount of postoperative drain fluid

AIM: To investigate whether the routine use of fibrin glue applied onto the hepatic resection area can diminish postoperative volume of bloody or biliary fluids drained via intraoperatively placed perihepatic tubes and can thus lower the complication rate.METHODS: Two groups of consecutive patients with a comparable spectrum of recent hepatic resections were compared: (1) 13 patients who underwent application of fibrin glue immediately after resection of liver parenchyma;(2) 12 patients who did not. Volumes of postoperative drainage fluid were determined in 4-h intervals through 24 h indicating the intervention caused bloody and biliary segregation.RESULTS: Through the first 8 h postoperatively, there was a tendency of higher amounts of fluids in patients with no additional application of fibrin glue while through the following intervals, a significant increase of drainage volumes was documented in comparison with the first two 4-h intervals, e.g., after 12 h, 149.6 mL +/-110 mL vs 63.2 mL +/-78 mL. Using fibrin glue, postoperative fluid amounts were significantly lower through the postoperative observation period of 24 h (851 mL +/-715 mL vs 315 mL +/-305 mL).CONCLUSION: For hepatic resections, the use of fibrin glue appears to be advantageous in terms of a significant decrease of surgically associated segregation of blood or bile out of the resection area. This might result in a better outcome.

Biocompatibility Studies on Fibrin Glue Cultured with Bone Marrow Mesenchymal Stem Cells in Vitro

Summary: By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro, the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.

Endoscopic fibrin glue injection for closure of pancreatocutaneous fistula following transgastric endoscopic necrosectomy

Transgastric endoscopic necrosectomy has been recently introduced as the effective and alternative management of infected pancreatic necrosis and pancreatic abscess. However,up to 40% of patients who undergo endoscopic necrosectomy may need an additional percutaneous approach for subsequent peripancreatic fluid collection or non-resolution of pancreatic necrosis. This percutaneous approach may lead to persistent pancreatocutaneous fistula,which remains a serious problem and usually requires prolonged hospitalization,or even open-abdominal surgery. We describe the first case of pancreatocutaneous fistula and concomitant abdominal wall defect following transgastric endoscopic necrosectomy and percutaneous drainage,which were endoscopically closed with fibrin glue injection via the necrotic cavity.

Successful steroid treatment for acute fibrinous and organizing pneumonia: A case report

BACKGROUND Since the acute fibrinous and organizing pneumonia(AFOP) was first described by Beasley in 2002, some case reports of patients aged from 38 d to 80 years have been published worldwide, but there is still no standard therapy for this disease and the treatment methods remain controversial. Both steroid and immunosuppressive agents, such as cyclophosphamide or mycophenolate mofetil, have been reported to be effective in some studies, but with many side effects, especially in patients of advanced age. CASE SUMMARY We herein report an 81-year-old female patient who was admitted to our hospital due to dry cough, and breathlessness for 1 mo. She was treated with broadspectrum antibiotics and anti-fungal therapy, but without improvement in both symptoms and radiological findings, and her respiratory status worsened, and she required bed rest almost the whole day. Computed tomography-guided percutaneous needle lung biopsy was performed and histopathology examination confirmed the diagnosis of AFOP. She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications. CONCLUSION We conclude that complete remission of AFOP can be achieved by steroid monotherapy in patients of advanced age.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

Therapeutic Effectiveness of Leukocyte-and Platelet-rich Fibrin for Diabetic Foot Ulcers:A Retrospective Study

Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical conditions.

Flapless immediate implant placement into fresh molar extraction socket using platelet-rich fibrin: A case report

BACKGROUND There are some challenges concerning immediate implant placement in the molar region.Platelet-rich fibrin(PRF),an autologous biomaterial,has been used widely for periodontal intra-bony defects,sinus augmentation,socket preservation,and gingival recession.However,the literature remains scarce for reports on immediate implants with PRF,particularly in the case of fresh molar extraction socket.CASE SUMMARY The patient was a 43-year-old woman with maxillary molar vertical crown-root fracture.She underwent flapless immediate implant placement into the fresh molar socket with PRF.At the follow-up visit 15 d post procedure,the vascularization of soft tissue was visible.There was no swelling or pain after the surgery.Six months postoperatively,the regeneration of bone and soft tissues was visible.Subsequently,the definitive restoration was placed.The patient was satisfied with the aesthetic outcomes.CONCLUSION The flapless immediate implant placement into the fresh molar socket with PRF is a feasible procedure.This case report demonstrates that PRF promotes bone and soft tissue regeneration apart from having an enhanced anti-inflammatory ability.Furthermore,the procedure involves a minimally invasive technique,thus reducing the surgical complexity.

Uterine artery embolization in residual arterio-venous fistula due to invasive mole using glue and polyvinyl alcohol particles: Case report

Gestational trophoblastic diseases (GTD) are one of the rare complications of pregnancy, which include partial and complete moles with their more aggressive counterparts termed as Gestational trophoblastic neoplasias (GTN). Their association with uterine vascular malformations is well recognised and should be suspected in appropriate clinical settings. Selective uterine artery embolization is a safe and effective alternative method of treatment in a patient with severe per vaginal bleeding from residual uterine vascular malformations due to GTN which has relative lower morbidity and mortality than surgical procedures. Here, we report a case of residual uterine arterio-venous malformation due to invasive mole detected by ultrasonography (US) and contrast enhancedMRI & referred to Interventional Radiology for Transcathetor arterial embolization.

血浆基质在牙髓根尖周病治疗中的应用

血浆基质作为一种自体血液离心产物,具有再生修复的功能,已被广泛应用于口腔颌面部软硬组织再生修复、皮肤美容等领域,并取得了较好的效果。目前,牙髓再生治疗和根尖手术已成为保存牙髓以及保存患牙的主要方法,生物活性材料的应用至关重要,血浆基质作为一种自体生物活性材料,较易获取,可塑性强,具有天然优势。血浆基质可应用于以下情况:①无法刺激根尖出血的根尖孔未闭合年轻恒牙的牙髓血运重建术;②存在骨缺损的根尖屏障术及大面积穿孔髓室底或根侧壁修补术;③大面积根尖病变,伴或不伴随牙周疾病患牙的根尖手术。因血浆基质为自身血液来源制品,使用方面无明显禁忌。虽然已有系统综述表明,相比传统血凝块,血浆基质作为天然再生支架,可有效促进牙髓根尖周病的再生性修复。然而,由于血浆基质的特性受不同制备方式的影响,其适用范围有所差异。此外,目前尚缺乏血浆基质长期的临床研究结果,且组织学证据较难获取,仍然需要大量的体内外研究进一步探索。本文将对不同血浆基质在牙髓再生、根尖手术中的骨组织再生等方面的应用进行阐述,以期为临床医生在适应证选择及预后评估时提供参考。

阿胶强骨口服液含药血清对胎鼠成骨细胞护骨素及护骨素配体mRNA表达的影响

目的研究阿胶强骨口服液含药血清对胎鼠成骨细胞中OPG、RANKL表达的影响,探讨阿胶强骨口服液治疗骨质疏松的分子机制。方法 3月龄Wistar大鼠(雌雄各半)30只,随机分为阿胶强骨口服液,雌激素,及生理盐水对照组,灌胃7d后,制备实验组和对照组的含药血清。将新生SD大鼠分离的颅骨成骨细胞,制成单细胞悬液,消化传代,取二代培养的成骨细胞,制成细胞悬液。培养细胞被分为5组,分别加同体积药液,对照组仅加培养液,继续培养。采用MTT比色分析、3H-胸腺嘧啶核苷(3H-TdR)渗入法测定成骨细胞增殖,用放免法测定细胞内BGP含量,RT-PCR测定胎鼠成骨细胞中OPG、RANKL mRNA的表达。结果阿胶强骨口服液含药血清以剂量依赖方式促进成骨细胞的增殖,与对照组相比,差异显著(P<0．05)。成骨细胞OPG基因mRNA表达在阿胶强骨口服液含药血清100ml／L时最强,与雌激素组比较无显著性差异(P>0 05),且明显高于对照组(P<0．05)。成骨细胞RANKL基因mRNA表达在1000ml／L阿胶强骨口服液含药血清与雌激素组比较无显著性差异(P<0 05),且明显低于对照组(P<0．05)。结论阿胶强骨口服液可在细胞水平上促进骨的合成代谢及前成骨细胞的有丝分裂,分子水平上调节 OPG／RANKL表达而治疗骨质疏松。

C端序列的删除对非出血重组蛇毒纤溶酶的影响

【目的】研究C端序列对非出血重组纤溶酶(rFⅡ)特异性、活性和热敏感性的影响。【方法】通过SOEingPCR方法构建删除C端序列的突变体,突变体和rFⅡ分别在P.pastoris中诱导表达。表达和纯化的蛋白用SDS-PAGE和Westerenblot进行鉴定。之后分析其生化特性。【结果】rFⅡ及突变体通过SDS-PAGE和Westerenblot得到证实。生化分析揭示:①突变体对显色底物N-(p-Tosyl)-Gly-Pro-Lys-pNA的催化效率(Kcat/Km)是rFⅡ的1.9倍;②突变体和rFⅡ对氧化的胰岛素B链拥有共同的优先裂解位点,可是在随后的裂解中开始展现差异;③突变体显示了更高的纤(原)活性;④热处理表明突变体相较rFⅡ对温度的增加更敏感;⑤通过圆二色谱测量,突变体的螺旋比例有所增加。【结论】删除的序列参与rFⅡ的特异性、活性和热敏感性,该序列可作为下一步优化的候选序列。

凝血酶在体外血栓制作中的应用:对降解时间的影响及其机制

目的观察体外在血栓制作中应用凝血酶对血栓溶解性的影响及其机制;对血浆纤维蛋白原水平与血栓中交联纤维蛋白含量进行相关分析,预测血栓溶解性的价值。另外,提出一种精确测定血栓中交联纤维蛋白含量的方法。方法 (1)红细胞比容35%～45%的健康人新鲜静脉血10 ml,平分为5份,取其中4份,3份分别加入高(75 u/ml)、中(50 u/ml)、低浓度(25 u/ml)凝血酶,1份加入生理盐水作为对照,摇匀,置于37℃水浴箱中3 h,使其凝固形成血栓。(2)剩余的1份血标本,应用Clauss法检测人血纤维蛋白原水平。(3)观察4组血栓之间机械性能的差别,包括弹性和塑性。(4)每个血栓分别切取一部分,修剪成重量为150 mg的正方体,磷酸缓冲液冲洗后,置于纤溶酶溶液中,在37℃水浴箱中孵育振荡,肉眼观察血栓降解过程。(5)记录血栓降解时间(包括血栓块消失时间和交联纤维蛋白絮状物消失时间),离心,取上清液,保存于-20℃。(6)解冻上清液,用蒸馏水稀释,应用酶联免疫法检测D二聚体浓度。(7)根据D二聚体浓度计算血栓中交联纤维蛋白含量。(8)对4组血栓交联纤维蛋白含量进行方差分析并两两比较;对4组血栓降解时间进行秩和检验并两两比较;对血浆纤维蛋白原水平与高凝血酶组血栓中的交联纤维蛋白含量进行相关分析。结果无凝血酶组血栓韧性差,易碎;应用凝血酶的3组血栓均具有良好的韧性。与无凝血酶组相比,高、中、低浓度凝血酶组血栓的降解时间和交联纤维蛋白含量均显著增加(P均<0.01);高、中浓度凝血酶组与低浓度凝血酶组相比,血栓的降解时间和交联纤维蛋白含量均显著增加(P均<0.01);高浓度凝血酶组与中浓度凝血酶组之间相比,血栓降解时间和纤维蛋白含量差异无统计学意义(P均>0.05)。血浆纤维蛋白原水平与高浓度凝血酶组血栓的交联纤维蛋白含量呈直线相关(r=0.681,P<0.001)。结论在体外溶栓实验中,应用凝血酶能通过增加血栓交联纤维蛋白含量延长血栓降解时间;在制作血栓时,凝血酶浓度的适宜范围为25 u/ml～50 u/ml,高于此浓度不能使血栓的韧性和降解时间进一步增加。血浆纤维蛋白原浓度越高,形成的血栓所含交联纤维蛋白含量越多,因此,血浆纤维蛋白原水平可作为预测血栓溶解性的指标。