Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Efficacy of Embolization in Acquired Uterine Vascular Malformations: An Experience in Tertiary Care Centre in India / Eficácia da embolização em malformações vasculares uterinas adquiridas: uma experiência em centro de atendimento terciário na Índia

Abstract Objective: To determine the efficacy of Uterine Artery Embolization in patients with bleeding acquired uterine arteriovenous malformations (AVMs). Methods: A prospective review of all patients who underwent Uterine Artery Embolization at our institution between July 2015 and April 2022 was performed. 225 patients were diagnosed with a uterine vascular malformation on doppler and corresponding MRI imaging. All patients underwent transcatheter embolization of the uterine arteries. Embolic agents in the 375 procedures included Histoacryl glue only (n = 326), polyvinyl alcohol (PVA) particles and Histoacryl glue (n = 29), PVA particles (n = 5), Gelfoam (n = 5), coils (n = 4), PVA particles and coils (n = 3), Histoacryl glue and Gelfoam (n = 2), and Histoacryl glue and coils (n = 1). Results: A total of 375 embolization procedures were performed in 225 patients. 90 patients required repeat embolization for recurrence of bleeding. The technical success rate of embolization was 100%. The clinical success rate was 92%: bleeding was controlled in 222 of 225 patients and three patients underwent a hysterectomy. 60 of the 225 patients had uneventful intrauterine pregnancies carried to term. The 210 patients who underwent successful embolization had no recurrence of bleeding at a median follow-up of 53 months (range, 5-122 months) after treatment. 15 patients were eventually lost to follow-up. One minor complication (0.4%) of non-flow-limiting dissection of the internal iliac artery occurred. Conclusion: Uterine Artery Embolization is a safe, effective, minimally invasive method to treat uterine AVMs with long-term efficacy, which can provide the preservation of fertility.

Dacryocystectomy: A fibrin glue-assisted subfascial excision

This article describes a technique of dacryocystectomy involving dissection within the subfascial plane, in which the lacrimal sac fascia is preserved and the orbital fat remains undisturbed. The lacrimal sac cavity was directly injected with Tisseel fibrin glue mixed with trypan blue. This led to sac distension and facilitated its separation from surrounding periosteal and fascial attachments. Staining the lacrimal sac epithelium improved definition of the mucosal lining. Transverse sections of the lacrimal sac specimen were histologically analyzed, which confirmed that dissection was completed within a subfascial plane. The technique herein described facilitates en bloc excision of the lacrimal sac without breaching the fascial plane that separates the sac from orbital fat.

Anterior lens capsule: Biological drape

Small perforations are often managed with cyanoacrylate glue - bandage contact lens (BCL). An additional layer with substances like sterile drape often enhances the strength of the glue. Herein, we describe a novel method of using anterior lens capsule as biological drape to secure perforation. The anterior capsule was secured from femtosecond laser–assisted cataract surgery (FLACS) and placed over the perforation after folding it twice. The area was dried and a small aliquot of cyanoacrylate glue was applied over it. The BCL was applied over it after the glue was dry. In our series of five patients, none of them needed repeat surgery and all cases healed by three months without vascularization. It is a unique technique to secure small corneal perforations.

A novel interlamellar oral mucosa graft surgery technique using fibrin glue for the treatment of trichiasis / Nova técnica cirúrgica de enxerto interlamelar de mucosa oral usando cola de fibrina para o tratamento de triquíase

ABSTRACT Purpose: The purpose of this study was to evaluate the long-term outcomes of patients with trichiasis treated with a modified interlamellar oral mucosa graft surgery technique using fibrin glue. Methods: A prospective study was conducted at the Oculoplastic Department of Ouro Verde Hospital Complex. Patients with recurrent trichiasis without entropion who did not respond to conventional therapy, underwent intermarginal lamellar splitting of the eyelid and oral mucous graft insertion with fibrin glue replacing sutures. They were then evaluated at 1-day, 1-week, 1-month, 6-month, and 4-year follow-ups. Graft adherence, symptom resolution, esthetic satisfaction, overall patient satisfaction, and trichiasis recurrence were assessed at 6-month and 4-year follow-ups. Results: Fifteen patients (a total of 19 eyes) were included, of whom 10 (66.7%) were female and 5 (33.3%) were male. The mean age was 75.4 ± 10.5 years (range, 54-98 years). Acquired trichiasis was the main cause. Of the patients with acquired trichiasis, 12 (86.7%) had chronic blepharitis, 2 (13.3%) had an undetermined cause, and one (6.7%) had trachomatous trichiasis. Most cases involved only one eyelid segment (89.4%) and =5 lashes (84.2%; minor trichiasis). No adverse reactions from the fibrin glue were reported and no sutures were required after graft placement. At 6 months, no graft failures occurred, 17 eyes of 13 patients (89.4%) showed good graft adherence, 2 eyes of 2 patients (10.5%) showed partial graft adherence, and 2 eyes of 1 patient (10.5%) had trichiasis recurrence. At 4-year follow-up, no graft failure occurred, 3 patients (3 eyes) were lost to follow-up, and 2 eyes of 2 patients (14.2%) had trichiasis recurrence. The 4-year cumulative success rate was 78.9%. Conclusions: The modified interlamellar surgery with fibrin glue showed a good long-term success rate. This technique reduces surgical time, facilitates smaller graft insertion, and therefore, should be considered for recalcitrant minor trichiasis without entropion.>

RESUMO Objetivo: O objetivo deste estudo foi avaliar os resultados a longo prazo da técnica cirúrgica modificada de enxerto interlamelar de mucosa oral usando cola de fibrina para o tratamento de triquíase. Métodos: Um estudo prospectivo foi realizado no Departamento de Óculo-plástica do Complexo Hospital Ouro Verde. Pacientes com triquíase recorrente sem entrópio, que não responderam à terapia convencional, foram submetidos à cirurgia com separação intermarginal das lamelas das pálpebras e inserção de enxerto de mucosa oral usando cola de fibrina, substituindo a sutura. Pacientes foram avaliados 1 dia, 7 dias, 1 mês, 6 meses e 4 anos após a cirurgia. A aderência do enxerto, resolução dos sintomas, satisfação estética, satisfação geral do paciente e recorrência de triquíase foram avaliados aos 6 meses e aos 4 anos. Resultados: Quinze pacientes (total de 19 olhos) foram incluídos, dos quais 10 (66.7%) eram do sexo feminino e 5 (33.3%) do sexo masculino. A média de idade foi 75.4 ± 10.5 anos (intervalo 54-98 anos). Triquíase adquirida foi a principal causa, da qual 12 pacientes apresentaram blefarite crônica (86.7%), 2 pacientes com causa indeterminada (13.3%) e 1 paciente com triquíase tracomatosa (6.7%). A maioria dos casos envolveu apenas um segmento da pálpebra (89.4%) e com =5 cílios (84.2%; triquíase menor). Nenhuma reação adversa foi reportada com o uso da cola de fibrina e nenhum caso necessitou de sutura após inserção do enxerto. Aos 6 meses, não houve nenhuma falha de enxerto, 17 olhos de 13 pacientes (89.4%) apresentaram boa aderência de enxerto, 2 olhos de 2 pacientes (10.5%) mostraram aderência parcial do enxerto e 2 olhos de 1 paciente (10.5%) apresentaram recorrência da triquíase. Aos 4 anos, não houve nenhuma falha de enxerto, 3 olhos de 3 pacientes tiveram perda de seguimento e 2 olhos de 2 pacientes (14.2%) apresentaram recorrência da triquíase. A taxa de sucesso acumulativa após 4 anos foi de 78.9%. Conclusão: A cirurgia modificada de enxerto interlamelar de mucosa oral usando cola de fibrina mostrou uma boa taxa de sucesso a longo prazo. Esta técnica reduz o tempo cirúrgico, facilita a inserção de enxertos menores e, portanto, deve ser considerada em triquíase menor sem entrópio resistente ao tratamento convencional.

Learning curve of CT-guided localization with medical glue for single pulmonary nodule before video-assisted thoracic surgery / 中国胸心血管外科临床杂志

@#Objective    To evaluate the learning curve of CT-guided medical glue localization for pulmonary nodule before video-assisted thoracic surgery (VATS). Methods    The clinical data of the patients with pulmonary nodules who underwent CT-guided medical glue localization before VATS in our hospital from July 2018 to March 2021 were retrospectively analyzed. The patients were divided into 3 groups: a group A (from July 2018 to August 2019), a group B (from September 2019 to June 2020) and a group C (from July 2020 to March 2021). The localization time, morbidity, complete resection rate and other indexes were compared among the three groups. Results    A total of 77 patients were enrolled, including 24 males and 53 females aged 57.4±10.1 years. There were 25 patients in the group A, 21 patients in the group B, and 31 patients in the group C. 77 pulmonary nodules were localized. There was no significant difference among the groups in the basic data (P>0.05). The localization time in the group C was 10.6±2.0 min, which was statistically shorter than that in the group A (15.4±4.4 min) and group B (12.9±4.3 min) (P<0.01). The incidence of complications in the group C was lower than that in the group A and group B (25.8% vs. 52.0% vs. 47.6%, P=0.04). The success rate of localization of the three groups was not statistically different (P=0.12). Conclusion    There is a learning curve in CT-guided medical glue localization for single pulmonary nodule before VATS. After the first 46 cases, the operation time can be shortened, and the incidence of complications can be decreased.

Application comparison of CT-guided localization with medical glue or puncture needle for pulmonary ground-glass nodules before thoracoscopic resection / 肿瘤研究与临床

Objective:To investigate the application value of CT-guided localization with medical glue or puncture needle before thoracoscopic pulmonary ground-glass nodule resection.Methods:The clinical data of 92 patients who underwent localization before thoracoscopic resection of pulmonary ground-glass nodules in Beijing Chao-Yang Hospital from June 2019 to November 2022 were retrospectively analyzed. According to the preoperative localization method, the patients were divided into puncture needle group (52 cases) and medical glue group (40 cases). The localization success rate, localization time and incidence rate of complications were compared between the two groups.Results:The success rate of localization in both groups was 100%. In puncture needle group, the guide wire of 1 case (1.9%) prolapsed, but it did not affect the surgical resection. The localization time of puncture needle group and medical glue group was (18±6) min and(14±5) min, and there was a statistical difference between the two groups ( t = 3.06, P = 0.003). The incidence of bleeding and pneumothorax in medical glue group was lower than that in puncture needle group [12.5% (5/40) vs. 38.5% (20/52), χ2 = 7.70, P = 0.009; 35.0% (14/40) vs. 71.2% (37/52), χ2 = 11.96, P = 0.001]. The incidence rate of irritating cough in was higher than that in puncture needle group [50.0% (20/40) vs. 11.5% (6/52), χ2 = 16.50, P < 0.05]. Conclusions:CT-guided localization with medical glue or puncture needle can achieve satisfactory results in the localization of pulmonary ground-glass nodule before thoracoscopic resection and help to improve the accuracy of surgical resection. The incidence rates of bleeding and pneumothorax of medical glue localization are lower than those of puncture needle localization.

Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy

Ubiquitin (Ub) and ubiquitin-like (Ubl) pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/inactivated. To date, >600 associated enzymes have been reported that comprise a hierarchical task network (e.g., E1-E2-E3 cascade enzymatic reaction and deubiquitination) to modulate substrates, including enormous oncoproteins and tumor-suppressive proteins. Several strategies, such as classical biochemical approaches, multiomics, and clinical sample analysis, were combined to elucidate the functional relations between these enzymes and tumors. In this regard, the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl pathways. Correspondingly, emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed essential. In the present review, we summarize and discuss the functions, clinical significance, and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug discovery. In particular, multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer therapy. The present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.

Discovery of small molecule degraders for modulating cell cycle / 医学前沿

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

Clinical outcome and course of Tenon’s patch graft in corneal perforation and descemetocele

Purpose: To assess the efficacy and clinical outcome of Tenon’s patch graft (TPG) in corneal perforation and descemetocele. Methods: In this retrospective study, medical records of 83 patients (85 eyes) who underwent TPG for corneal perforation (58, 68%) or descemetocele (27, 32%) between July 2018 and October 2021 were reviewed. Clinical examination and anterior segment optical coherence tomography (AS?OCT) were performed on every follow?up visit. Anatomical success was considered as the restoration of the structural integrity with the formation of scar and anterior chamber (AC). Results: The mean size of the corneal lesions (corneal perforation or descemetocele) was 4.20 ± 1.01 mm. The mean follow?up period was 9.2 ± 5.48 months. The common underlying etiologies were infectious keratitis in 48% and autoimmune disorders in 35% of cases. TPG successfully restored the globe integrity in 74 (87%) eyes (83% in perforation and 96% in descemetocele). Anatomical failure occurred in 11 eyes (13%). The failures were due to graft dehiscence (8 eyes), graft ectasia (1 eye), and scarring with flat AC (2 eyes). The median time to epithelialization and scar formation were 3 and 15 weeks, respectively. Logistic regression analysis showed few predictors for a successful outcome: descemetoceles, noninfective causes, viral keratitis in infectious etiology, and paracentral or peripheral lesions. Conclusion: TPG can be considered an effective and inexpensive treatment for restoring the structural integrity in the eyes with perforations and descemetoceles, particularly when the donor tissue is unavailable. AS?OCT is a valuable noninvasive tool for monitoring the graft status

Therapeutic effect of propolis on Staphylococcus aureus induced oxidative stress in kidney of BALB/c mice. A biochemical and histopathological study

Due to emerging drug resistance in pathogenic organisms, most of the second generation antibiotics are not effective in controlling the disease. As a consequence, the dosage and duration of drug intake has increased leading to drug induced toxicity and various side effects. A large number of natural products are being reported to ameliorate the toxicity and oxidative stress caused by antibiotics. Here, we explored the antioxidative potential of honey bee product propolis alone as well as in combination with antibiotics in Staphylococcus aureus infected BALB/c mice. For experimental design, mice were divided in to seven groups and decapitated after experimental period. Kidney was excised, homogenized and then used for different biochemical and histopathological estimations. Results observed after treatment with propolis and antibiotics were compared with those of S. aureus infected group. Results showed increase in lipid peroxidation, decrease in reduced glutathione levels and antioxidant enzymes such as; catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. On the contrary, treatment with propolis, led to reduction in levels of LPO and increase in activities of antioxidant enzymes. Also, histopathology of kidney and all kidney function enzymes were restored to near normal.

Comparison conventional endoscopic myringoplasty with fibrin glue supplemented endoscopic myringoplasty

Introduction: The fibrin tissue glues have been used in many surgeries to reinforce surgical sutures and tissue adhesion. Myringoplasty is the commonly done ear surgery for the perforations of the tympanic membrane, where no suturing is done between remnant membrane and graft. Aim: The aim of the study is to compare the results and effectiveness of this biological fibrin tissue glue in myringoplasty surgeries as a supplementary procedure to conventional endoscopic myringoplasty (CEM) surgeries. Materials and Methods: Seventy patients with chronic suppurative otitis media with tympanic membrane perforation without ossicular and mastoid involvement have been chosen. One group of 35 patients underwent CEM surgeries. In another group of 35 patients, biological fibrin tissue glue, TISSEEL, has been used as supplementary to the CEM surgeries, and the graft uptake rate and hearing improvement were evaluated and compared postoperatively. Results: The graft success rate at 3 months postoperatively was 91.42% in both the groups, that is, 32/35, and these values were not statistically significantly different (P = 1.00). There was a highly statistically significant hearing outcome before and after the surgery in both the CEM and the fibrin tissue glue supplemented endoscopic myringoplasty groups. However, there was no statistically significant change in hearing outcomes between the two groups. Conclusion: In our study, we have got more or less similar results compared with the results of the studies on routine CEM cases. But the high-cost nature of the commercially available fibrin tissue glue makes it difficult to recommend for use in all routine endoscopy myringoplasty cases

Management of descemetocele: Our experience and a simplified treatment algorithm

Purpose: To formulate a treatment algorithm for the management of descemetocele. Methods: This was a prospective interventional study that was conducted at a tertiary eye?care center. All consecutive cases of descemetocele during the study period (April 1, 2017–March 31, 2018) were evaluated for the following parameters: age, sex, previous medical or surgical therapy, risk factors, preexisting ocular diseases, location, site and size of descemetocele, interventions undertaken, visual acuity, and the fellow eye status. The surgical modalities and fellow eye status were correlated individually with therapeutic and functional outcomes, based on which a treatment algorithm was formulated. Results: The study included 24 eyes of 24 patients (19M, 5F) with a median age of presentation of 45 years. The mean follow?up duration was 6.79 ± 3.97 months (3–12 months). The most common cause of descemetocele was microbial keratitis (66.66%), and most cases were central (50%), small (58.33%), and non?perforated (79.16%). The surgical interventions undertaken were cyanoacrylate glue (CG, 37.5%), penetrating keratoplasty (PKP, 33.33%), patch graft (16.66%), and deep anterior lamellar keratoplasty (DALK, 12.5%). Therapeutic success was noted in 13/24 eyes (54.16%). Final visual acuity > 3/60 was seen in 25% cases. Suboptimal therapeutic (P = 0.07) and visual (P = 0.34) outcomes were noted in subjects with non?functional fellow eye. Conclusion: PKP was preferred for descemetoceles with active microbial keratitis and extensive infiltrates, while CG and DALK were undertaken for healed microbial keratitis, neurotrophic keratitis, and ocular surface disorders with partial limbal stem cell deficiency (LSCD). For total LSCD, amniotic membrane graft was preferred.

Fibrin glue assisted amniotic membrane graft reconstruction of conjunctival fornix and canthus following excision of conjunctival tumours

Conjunctival tumors involving non?limbal locations, such as the fornix and canthus, are typically excised using a “non?touch” technique, often with a wide surgical margin. Reconstruction of these large defects can be difficult due to the contour of the ocular surface and are often complicated by shortening of the fornix, symblepharon formation, and restriction of eye movements. In our experience, the use of amniotic membrane grafts combined with the sealant properties of fibrin glue such as Tisseel® has improved our surgical outcomes during the reconstruction phase. We would like to highlight and describe our surgical technique using fibrin glue and squint hooks to aid amniotic membrane graft reconstruction for surgically challenging locations in the fornix and canthus following excision of conjunctival lesions, with excellent surgical outcomes.

A glued technique of external dacryocystorhinostomy

Purpose: Fibrin glue was used for anastomosis of lacrimal sac and nasal mucosal flaps and was compared with the conventional suture technique in external dacryocystorhinostomy. Methods: A prospective interventional randomized control study in which 50 consecutive patients of primary acquired nasolacrimal duct obstruction (PANDO) were equally allocated into two groups. The case group underwent glued technique of external dacryocystorhinostomy (Ext DCR) in which fibrin glue was used for the apposition of the anterior lacrimal sac and nasal mucosal flaps. In the control group, conventional technique of Ext DCR was used to suture the flaps. Functional success was assessed by improvement in epiphora and fluorescein dye disappearance test (FDDT), whereas anatomical success was assessed by lacrimal irrigation and endoscopic view of the osteotomy site. Results: The anatomical success in both the groups was 92%, whereas the functional success was 92% in the case group and 88% in the control group. The difference in the success rates between the two groups was statistically non?significant. Conclusion: Glued technique of Ext DCR is a simple and easy alternative to suturing of the flaps. Though the final outcome was comparable in both the groups, glue can be especially useful in uncooperative cases, in cases of excessive bleeding, or in situations where the flaps are very thin or have become friable

Sutureless and glue-free limbal-conjunctival autograft in primary and recurrent pterygium: A pilot study

Purpose: To evaluate and analyze the outcomes of sutureless and glue?free limbal?conjunctival autografting in cases of primary as well as recurrent pterygium. Methods: This prospective interventional study was carried out between February 2019 and February 2020 at a tertiary care hospital in North India. A total of 70 patients with pterygium underwent sutureless and glue?free limbal?conjunctival autograft. The patients were divided into two groups: group 1 patients with primary pterygium (n = 45), group 2 patients with recurrent pterygium (n = 25). The patients were followed up till 12 months postoperatively. Results: The mean age of the patients in group 1 and group 2 was 37.04 ± 8.69 years and 32.52 ± 6.49 years, respectively (P = 0.04). Postoperatively, no recurrence was recorded in group 1. Recurrence was noticed in two patients (8%) of group 2. The BCVA changed from 78.73 ± 9.86 letters to 80.15 ± 7.29 letters (P = 0.45) and from 79.6 ± 6.44 letters to 79.8 ± 5.86 letters (P = 0.45) in group 1 and group 2, respectively. Graft edema was found in seven (15.55%) cases of group 1 and four (16%) cases of group 2. Graft retraction was found in two (4.44%) cases of group 1 and three (12%) cases of group 2. Conclusion: Sutureless and a glue?free limbal?conjunctival autograft is a safe and effective treatment option for primary as well as recurrent pterygium.

The use of surgical adhesive and suture fixing meshes to the abdominal wall: an experimental study in rats / O uso de cola cirúrgica e sutura na fixação de tela em parede abdominal: estudo experimental em ratos

ABSTRACT - BACKGROUND: Proper fixation of the surgical mesh determines the success of a herniorrhaphy. Understanding the inflammatory response and the mechanical properties of the mesh helps to define whether a fixation method is superior. AIM: This study aimed to evaluate the healing of defects in the abdominal wall of rats, comparing the repair of macroporous polypropylene meshes fixed with surgical glue and polypropylene thread. METHODS: In 20 Wistar rats, a defect was produced in the abdominal wall, with the integrity of the parietal peritoneum. For correction, the meshes were fixed with surgical glue (2-octyl cyanoacrylate) (subgroup C1), or polypropylene suture (subgroup C2). The two subgroups of 10 animals were euthanized on the 90th postoperative day, and the fragments of the abdominal wall were submitted to macroscopic, histological, and tensiometric analysis. RESULTS: Macroscopic analysis did not show any abnormalities. Tensiometry on the 90th postoperative day in subgroup C1 showed mean rupture tension of 28.47N and in subgroup C2 32.06N (p=0.773). The inflammatory process score revealed that both groups are in the subacute phase (p=0.380). CONCLUSION: The fixation of a polypropylene macroporous mesh to repair an abdominal wall defect can be performed with surgical glue (2-octyl cyanoacrylate) or polypropylene suture, both methods being equally effective.

RESUMO - RACIONAL: A adequada fixação da tela cirúrgica determina o sucesso de uma herniorrafia. Entender a resposta inflamatória e as propriedades mecânicas da tela contribui para definir se há superioridade de um método de fixação. OBJETIVO: Avaliar a cicatrização de defeitos em parede abdominal de ratos, comparando-se o reparo das telas de polipropileno macroporosas fixadas com cola cirúrgica e fio de polipropileno. MÉTODOS: Foi produzido defeito na parede abdominal de 20 ratos Wistar com integridade do peritônio parietal. Na correção, as telas foram fixadas com cola cirúrgica 2-octil cianoacrilato (C1) ou sutura (C2). Os dois subgrupos de 10 animais foram eutanasiados no 90º dia de pós-operatório e os fragmentos da parede abdominal foram submetidos a análise macroscópica, histológica e tensiométrica. RESULTADOS: A análise macroscópica não mostrou qualquer anormalidade. A tensiometria no 90º dia de pós-operatório no subgrupo C1 demonstrou tensão média de ruptura de 28,47N e no subgrupo C2 de 32,06N (p=0,773). O escore de processo inflamatório revelou que ambos os grupos se encontram na fase subaguda (p=0,380). CONCLUSÃO: A fixação de tela macroporosa de polipropileno para reparo de defeito em parede abdominal pode ser realizada com cola cirúrgica (2-octil cianoacrilato) ou sutura de polipropileno, sendo ambos os métodos igualmente eficazes.

Progress of discovery of molecular glues from natural products and their derivatives / 药学学报

Molecular glues are a class of small molecules that induce the formation of protein-protein interactions to confer new biological function or therapeutic effects. As a unique pharmacological modality, molecular glues could target proteins without druggable binding pockets. It exhibits a variety of functions, including regulating signal transduction, stabilization or degradation of targeted proteins, through sticking different proteins together. This review will summarize the development and current status of molecular glues derived from natural products and analogs by illustrating the discovery and interaction mechanism. We hope to present a systematic view, provide valuable clues for researchers and encourage them to explore more efficient and rational molecular glue discovery strategies.

Application of CT-guided Localization with Medical Glue for Single and Two or More Small Pulmonary Nodules before Video-assisted Thoracic Surgery / 中国肺癌杂志

BACKGROUND@#The localization of pulmonary nodules is related to whether the lesions can be found and removed accurately and quickly. It is an important link for the success of minimally invasive video-assisted thoracic surgery (VATS). This study investigated the feasibility of medical glue localization under VATS video-assisted thoracoscopic computed tomography (CT) guidance for single pulmonary nodule and more than two pulmonary nodules, and compared with the accuracy and safety of single nodule localization.@*METHODS@#A retrospective analysis of the clinical data of patients who underwent unilateral CT-guided medical glue localization before VATS from November 2018 to March 2021 were performed, the patients was divided into multiple pulmonary nodules group (localized nodules ≥2) and single pulmonary nodule group according to the number of localized nodules. The localization time, success rate and complication rate of the two groups were compared.@*RESULTS@#There were 126 nodules in the two groups, including 62 in single pulmonary nodule group and 64 in multiple pulmonary nodules group. The average single nodule localization time was (13.23±4.5) min in single pulmonary nodule group and (10.52±2.8) min in multiple pulmonary nodules group, the difference between the two groups is statistically significant (P<0.05). The localization success rate of single pulmonary nodule group and multiple pulmonary nodules group were 100% and 98.4% separately, the difference between the two groups was not statistically significant (P>0.05). All VATS were successfully completed after localization. The incidence of pneumothorax was higher in multiple pulmonary nodules group than in single pulmonary nodule group (P=0.07).@*CONCLUSIONS@#Compared with localization of single lung nodule, unilateral CT-guided medical glue localization for multiple pulmonary nodules before VATS is also feasible and accuracy, it is worthy of clinical application. But the higher rate of pneumothorax should be paid attention to.

Morphometric study of rat sciatic nerve recovery after three nerve repair techniques: epineural suture, polyethylene glycol hydrogel and fibrin sealant / Estudio morfométrico de la recuperación del nervio ciático de rata después de tres técnicas de reparación nerviosa: sutura epineural, hidrogel de polietilenglicol y sellante de fibrina

SUMMARY: The effectiveness of microsurgical technique has a direct impact on the recovery of the injured peripheral nerve. The aim of our study was to investigate the result of sciatic nerve regeneration in rats after complete neurotomy and after nerve repair techniques including: 1) epineural suture; 2) polyethylene glycol hydrogel (PEG) (DuraSeal); 3) fibrin sealant (Tisseel). The cross-section of distal sciatic nerve was studied at 14th, 30th and 60th days after nerve repair. Morphometry of myelinated nerve fibers in the distal stump of the sciatic nerve was performed. A significant increase in the number of myelinated nerve fibers was found, especially between 14 and 30 days. The density of myelinated nerve fibers in the distal stump at day 60 was significantly higher after using nerve repair technique including PEG and fibrin versus epineural suture (29.2 % and 32.1 % versus 21.5 %, P <0.05), and a higher level of remyelination of nerve fibers observed in the group with PEG. On day 60, complete elimination of PEG and fibrin sealant was not observed, encapsulation was found around the clusters of hydrogel. Thereby, three peripheral nerve repair techniques were equally effective, only with the use of PEG remyelination of nerve fibers was increasing.

RESUMEN: La efectividad de la técnica microquirúrgica tiene un impacto directo en la recuperación del nervio periférico lesionado. El objetivo de nuestro estudio fue investigar el resultado de la regeneración del nervio ciático en ratas después de una neurotomía completa y después de técnicas de reparación nerviosa que incluyeron: 1) sutura epineural; 2) hidrogel de polietilenglicol (PEG) (DuraSeal); 3) sellante de fibrina (Tisseel). La sección transversal del nervio ciático distal se estudió a los 14, 30 y 60 días después de la reparación del nervio. Se realizó la morfometría de fibras nerviosas mielinizadas en el muñón distal del nervio ciático. Se observó un aumento significativo en el número de fibras nerviosas mielinizadas, especialmente entre los 14 y 30 días. La densidad de las fibras nerviosas mielinizadas en el muñón distal en el día 60 fue significativamente mayor después de usar una técnica de reparación nerviosa que incluye PEG y fibrina en comparación con la sutura epineural (29,2 % y 32,1 % versus 21,5 %, P <0,05), y un mayor nivel de remielinización del nervio en fibras observadas en el grupo con PEG. El día 60, no se observó la eliminación completa de PEG y sellador de fibrina, se encontró encapsulación alrededor de los grupos de hidrogel. Por lo tanto, tres técnicas de reparación de nervios periféricos fueron igualmente efectivas, solo que aumentaba la remielinización de fibras nerviosas con PEG.