Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Fanconi Anemia: Exploration of DNA Repair Pathways from Genetic Diseases to Cancer and Prospects for Treatment / 肿瘤防治研究

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Reconstruction and analysis of K-Clip surgery process based on finite element method / 中国胸心血管外科临床杂志

@#Objective     To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods     Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion     For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.

The applications of the plasma matrix in the treatments of dental pulp and periapical diseases / 口腔疾病防治

@#The plasma matrix is a kind of autologous blood conduct. It has been widely used in maxillofacial tissue regeneration, skin cosmetology and some other fields. Recently, to preserve the dental pulp as well as the teeth, pulp regeneration therapy and apical surgery have become increasingly important as well as the applications of bioactive materials. As a kind of autologous bioactive material, the plasma matrix has some natural advantages as it is easy to obtain and malleable. The plasma matrix can be used in the following cases: ①pulp revascularization of young permanent teeth with open apical foramina that cannot stimulate apical bleeding; ② apical barrier surgery with bone defects and large area perforation repair with bone defects or root sidewall repair surgery; ③ apical surgeries of teeth with large area of apical lesions, with or without periodontal diseases. The plasma matrix is a product derived from our blood, and there are no obvious contraindications for its use. Several systematic reviews have shown that the plasma matrix can effectively promote the regenerative repair of dental pulp in patients with periapical diseases. However, the applications of plasma matrix are different because its characteristics are affected by different preparation methods. In addition, there is still a lack of long-term clinical researches on the plasma matrix, and the histological evidences are difficult to obtain, so a large number of in vitro and in vivo experimental studies are still needed. This article will describe the applications of different kinds of plasma matrix for dental pulp regeneration and bone tissue regeneration in apical surgeries to provide references for clinicians in indication selection and prognosis evaluation.

Reconstruction of rat calvarial defects utilizing an ultraviolet-cured hydrogel loaded with bone marrow mesenchymal stem cells / 口腔疾病防治

Objective@#To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials.@*Methods@#This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation.@*Results@#SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P<0.05). Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone, primarily consisting of fibrous connective tissue, at the defect edge in the control group.@*Conclusion@#Photocuring hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Early clinical outcomes of the domestic KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation: A single-arm, prospective, single-group target value clinical trial / 中国胸心血管外科临床杂志

@#Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Mitral transcatheter edge-to-edge repair: A state of art and strategic principles / 中国胸心血管外科临床杂志

@#Transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) is known as M-TEER. Its strengths include: precise targets and fewer implants; simple and clear principles for catheterization; originating from dependable medical concepts and broad applicability. Furthermore, TEER offers advantages in real-time hemodynamic and effectiveness measurement throughout the procedure over surgical edge-to-edge repair (SEER). When it comes to patients with degenerative mitral regurgitation , M-TEER should aim to deliver more optimum procedural outcomes. In functional mitral regurgitation, a modest transvalvular gradients or moderate residual shunt can be tolerated with M-TEER, which reduces the risk of problems and has no bearing on the patient's prognosis.

Mechanism of Promoting Chronic Refractory Wound Repair by Polysaccharides in Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

A chronic refractory wound is caused by continuous skin damage. At the same time， it may be formed due to repeated infection， vascular insufficiency， diabetes， tumors， chronic osteomyelitis， and other reasons， resulting in wound repair interruption and recovery delay. Chronic refractory wound seriously affects the quality of life of patients and consumes a lot of medical resources. Polysaccharides in traditional Chinese medicine （TCM） are the effective components of most TCM. Modern pharmacological studies have found that polysaccharides contained in TCM have anti-inflammatory， antioxidant， anti-radiation， hypoglycemic， antiviral， anti-tumor， hypolipidemic， and immunomodulatory effects. Through the summary and analysis of the literature， it was found that the mechanism of polysaccharides in TCM to promote chonic refractory wound repair was mainly realized from the following aspects： firstly， regulating inflammatory cytokines like interleukin-4 （IL-4）， interleukin-10 （IL-10）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） or regulating macrophage-related inflammatory proteins and chemotactic proteins like MIP-2， MCP-1， to shorten the inflammatory period. Secondly， activating growth factors like platelet-derived growth fator （PDGF）， basic fibroblast growth factor （bFGF）， TGF-α， and vascular endothelial growth factor （VEGF） to recruit endothelial cells and fibroblasts into tissue proliferation. Thirdly， activationg VEGF and its downstream receptor vascular endothelial growth factor receptor-1 （VEGFR-1） and vascular endothelial growth factor receptor-2 （VEGFR-2）-mediatated protein kinase C/extracellular regulated kinases （PKC/ERK） signaling pathway or promoting angiogenesie and improving wound blood flow through angiotensin （ANG）. Fourthly， promoting the ablility of collagen synthesis by enhancing the secretion of hydroxyproline and hyaluronic acid （HA） from fibroblasts （FB） and regulating relevant matrix metalloenzymes and their enzyme inhibitor to regulate the extracellular matrix. Fifthly， eliminating free radiccals to reduce the damage caused by oxidative stress to tissue. Sixthly， enhancing the phagocytic ability of macrophages， the activity of natural killer cells， and the proliferation of T cells to improve the defense ability of tissue. Polysaccharides in TCM can repair wounds in many ways at the same time. Its advantage lies in the multiple targets and multiple pathways. It is expected that the research will pay more attention to the mechanism of wound repair by polysaccharide components in TCM when improving the treatment of chronic refractory wounds.

Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum

ABSTRACT Purpose: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. Methods: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. Results: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. Conclusion: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Mechanism of Shikonin on spinal cord injury in rats based on TNFR/RIPK1 pathway / 中国骨伤

OBJECTIVE@#To explore the effect of shikonin on the recovery of nerve function after acute spinal cord injury(SCI) in rats.@*METHODS@#96 male Sprague-Dawley(SD)rats were divided into 4 groups randomly:sham operation group (Group A), sham operation+shikonin group (Group B), SCI+ DMSO(Group C), SCI+shikonin group (Group D).The acute SCI model of rats was made by clamp method in groups C and D . After subdural catheterization, no drug was given in group A. rats in groups B and D were injected with 100 mg·kg-1 of shikonin through catheter 30 min after modeling, and rats in group C were given with the same amount of DMSO, once a day until the time point of collection tissue. Basso-Beattie-Bresnahan(BBB) scores were performed on 8 rats in each group at 6, 12, and 3 d after moneling, and oblique plate tests were performed on 1, 3, 7 and 14 d after modeling, and then spinal cord tissues were collected. Eight rats were intraperitoneally injected with propidine iodide(PI) 1 h before sacrificed to detection PI positive cells at 24 h in each group. Eight rats were sacrificed in each group at 24 h after modeling, the spinal cord injury was observed by HE staining.The Nissl staining was used to observe survivor number of nerve cells. Western-blot technique was used to detect the expression levels of Bcl-2 protein and apoptosis related protein RIPK1.@*RESULTS@#After modeling, BBB scores were normal in group A and B, but in group C and D were significantly higher than those in group A and B. And the scores in group D were higher than those in group C in each time point (P<0.05). At 12 h after modeling, the PI red stained cells in group D were significantly reduced compared with that in group C, and the disintegration of neurons was alleviated(P<0.05). HE and Nissl staining showed nerve cells with normal morphology in group A and B at 24h after operation. The degree of SCI and the number of neuronal survival in group D were better than those in group C, the difference was statistically significant at 24h (P<0.05). The expression of Bcl-2 and RIPK1 proteins was very low in group A and B;The expression of RIPK1 was significantly increased in Group C and decreased in Group D, with a statistically significant difference (P<0.05);The expression of Bcl-2 protein in group D was significantly higher than that in group C (P<0.05).@*CONCLUSION@#Shikonin can alleviate the pathological changes after acute SCI in rats, improve the behavioral score, and promote the recovery of spinal nerve function. The specific mechanism may be related to the inhibition of TNFR/RIPK1 signaling pathway mediated necrotic apoptosis.

Study on injectable chitosan hydrogel with tendon-derived stem cells for enhancing rotator cuff tendon-to-bone healing / 中国修复重建外科杂志

OBJECTIVE@#To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits.@*METHODS@#TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties.@*RESULTS@#CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05).@*CONCLUSION@#TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.

Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back / 中国修复重建外科杂志

OBJECTIVE@#To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.@*METHODS@#Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.@*RESULTS@#All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.@*CONCLUSION@#The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.

Procedural and long-term outcomes of elective endovascular abdominal aortic aneurysm repair in octogenarians / Resultados perioperatorios y a largo plazo de la reparación electiva endovascular del aneurisma de aorta abdominal en octogenarios

Abstract Objective: The aim of the study was to compare the immediate and long-term outcomes of endovascular aneurysm repair (EVAR) between patients under and over the age of 80 with abdominal aortic aneurysm (AAA). Methods: From 2011 to 2017, we conducted a retrospective cohort study with AAA patients who received elective EVAR. Primary outcomes included hospital mortality, length of stay, acute kidney injury, and the need for re-interventions. Secondary outcomes included aneurysm-related mortality, acute myocardial infarction, stroke, acute limb ischemia, and prolonged mechanical ventilation. Results: A total of 77 (62.6%) patients under the age of 80 years old and 46 (37.4%) octogenarians were included in the study. The male gender and AAA diameter did not differ among groups (92.2% vs. 82.6%, p = 0.11 and 5.4 cm [4.9-6.2 cm] vs. 5.4 cm [5-6 cm], p = 0.53, respectively). The younger patients had a higher prevalence of tobacco use (72.7% vs. 41.7%, p = 0.01). There were no deaths during the index hospitalization. The incidence of reinterventions (5.3% vs. 15.2%, p = 0.11) and acute kidney injury (14.3% vs. 23.9%, p = 0.18) did not differ between groups, but the length of stay was longer for octogenarian patients (3 days [2-4] vs. 2 days [2-3, p = 0.04]). Endoleaks were the most common cause for re-interventions (81.8%), with a prevalence of 34% across the entire cohort. There were no differences in any of the secondary outcomes between groups. Conclusion: In octogenarian patients with AAA, EVAR represents a safe procedure both during the index hospitalization and during long-term follow-up.

Resumen Objetivo: Comparar los resultados inmediatos y a largo plazo de la reparación endovascular del aneurisma de aorta abdominal (REVA) entre pacientes menores de 80 años y octogenarios. Método: Cohorte retrospectiva que incluyó pacientes con aneurisma de aorta abdominal (AAA) sometidos a REVA electiva desde 2011 hasta 2017. Se evaluaron como punto finales primarios la mortalidad hospitalaria, la duración de la estadía hospitalaria, la incidencia de insuficiencia renal aguda y el requerimiento de reintervenciones. Los puntos finales secundarios incluyeron la mortalidad asociada al aneurisma, infarto agudo de miocardio, accidente cerebrovascular, isquemia arterial aguda de las extremidades y ventilación mecánica prolongada. Resultados: Se incluyeron 77 (62.6%) pacientes menores de 80 años y 46 (37.4%) octogenarios. La prevalencia de sexo masculino y el diámetro del AAA no difirieron entre ambos grupos (92.2% vs. 82.6%, p = 0.11 y 5.4 cm [4.9-6.2 cm] vs. 5.4 cm [5-6 cm], p = 0.53, respectivamente). Los pacientes más jóvenes presentaron una mayor prevalencia de tabaquismo (72.7% vs. 41.7%, p = 0.01). No se registraron muertes durante la hospitalización índice. La incidencia de reintervenciones (5.3% vs. 15.2%, p = 0.11) e insuficiencia renal aguda (14.3% vs. 23.9%, p = 0.18) no difirieron entre ambos grupos, pero la estadía hospitalaria fue más prolongada en pacientes octogenarios (3 días [2-4 días] vs. 2 días [2-3 días], p = 0.04). La causa más frecuente de reintervenciones fue la presencia de endofugas (81.8%), con una prevalencia del 34% en toda la cohorte. No se observaron diferencias en ninguno de los puntos finales secundarios entre ambos grupos. Conclusión: En pacientes octogenarios con AAA, la REVA presentó un buen perfil de seguridad perioperatorio y a largo plazo.

Tratamiento endovascular de aneurismas con anatomía aórtica compleja / Endovascular treatment of aneurysms with complex aortic anatomy

RESUMEN Introducción: la anatomía arterial es la principal limitante para el abordaje aórtico endovascular estándar. Presentamos nuestra experiencia para la reparación endovascular de aneurismas aórticos complejos. Material y métodos: estudio observacional retrospectivo en pacientes con aneurismas complejos (yuxta/pararrenales y toracoabdominales) tratados en forma consecutiva mediante: endoprótesis fenestradas (FEVAR), ramificadas (BEVAR), con EndoAnchors (ESAR), o en chimenea (ChEVAR). La decisión de la técnica fue determinada con base en la anatomía arterial. Resultados: se evaluaron los últimos 50 procedimientos (6 mujeres; edad promedio 71,3 años; diámetro 69,6mm; 3 pacientes con aneurismas complicados), de los cuales 22 recibieron FEVAR (2,8 fenestraciones / paciente), 11 BEVAR, 11 ESAR y 6 ChEVAR (1,8 chimeneas /paciente). La tasa de éxito técnico fue del 100% (ausencia de endoleak I o III con permeabilidad adecuada de los vasos viscerales). A 30 días 3 pacientes fallecieron (6%). Durante el seguimiento, 5 pacientes presentaron oclusión de la arteria renal, repermeabilizada en 4. Cuatro pacientes desarrollaron un endoleak tipo IA (3 ESAR secundarios y un ChEVAR), un paciente un endoleak IC y un cuarto uno IIIB (22%, 3 de los 11 ESAR, ninguno de los FEVAR industriales). En el análisis de supervivencia, la supervivencia global fue del 88,6% al año, y libre de reoperación del 86,5%. Conclusiones: se trata de la primera publicación en nuestro medio que muestra un enfoque global del paciente con un aneurisma de aorta complejo, de acuerdo con sus características anatómicas. Estas tecnologías ya desempeñan un papel primario en el tratamiento de estos pacientes.

ABSTRACT Background: Arterial anatomy is the main limiting factor for standard endovascular aortic (EVAR) approach. We present our experience for endovascular repair of complex aortic aneurysms. Material and Methods: This is a retrospective observational study in patients with complex aneurysms (juxta/pararenal and thoracoabdominal) treated consecutively with: fenestrated (FEVAR), branched (BEVAR), EndoAnchors (ESAR), or chimney (ChEVAR) stents. The decision of the technique was determined based on the arterial anatomy. Results: The last 50 procedures were evaluated (6 women; mean age 71.3 years; diameter 69.6 mm; and 3 patients with complicated aneurysms), among whom 22 received FEVAR (2.8 fenestrated stents/patient), 11 BEVAR, 11 ESAR and 6 ChEVAR (1.8 chimney stents/patient). Technical success rate was 100% (absence of type I or III endoleak with adequate patency of the visceral vessels). Three patients died within the first 30 days (6%). During follow-up, 5 patients presented with renal artery occlusion, treated successfully in 4 cases. Four patients developed type IA endoleak (3 secondary ESAR and one ChEVAR), one patient IC endoleak and almost a quarter of cases type IIIB endoleak (22%, 3 out of 11 patients receiving ESAR, none of the industrial FEVAR group). In survival analysis, overall survival analysis was 88.6% at one year, and 86.5% of cases were free from reoperation. Conclusions: This is the first publication in our setting that shows a global approach to the patient with complex aortic aneurysm, according to the anatomical characteristics. These technologies already play a primary role in the treatment of these patients.

Manejo del aneurisma de aorta abdominal sintomático no roto: últimos adelanto / Management of symptomatic unruptured abdominal aortic aneurysms: state of the art

RESUMEN El aneurisma de aorta abdominal (AAA) sintomático no roto es una patología que involucra a aquellos pacientes con AAA intacto, pero que presentan dolor abdominal y/o lumbar atribuido al aneurisma. Esta forma de presentación clínica es po tencialmente mortal dado que su etiopatogenia comprende cambios agudos en la pared aórtica, incluyendo inflamación, lo que incrementa la probabilidad de ruptura inminente. Está claro que estos pacientes deben ser derivados a reparación del AAA. Sin embargo, el momento de la intervención es controvertido. Por lo tanto, el objetivo del presente trabajo fue revisar la información actualizada sobre el abordaje diagnóstico-terapéutico del AAA sintomático no roto.

ABSTRACT Symptomatic unruptured abdominal aortic aneurysm (AAA) refers to a group of patients with intact AAA but who present abdominal and/or lumbar pain attributed to the aneurysm. This form of clinical presentation is potentially fatal since its etiopathogenesis, involving acute changes in the aortic wall, including inflammation, increases the probability of impending rupture. It is clear that these patients should be referred to AAA repair. However, the timing of the intervention is contro versial. Therefore, the aim of the present work was to review updated information on the diagnostic-therapeutic approach of symptomatic unruptured AAA.

Comparative Assessment of Contact Osteogenesis at the Titanium Implant-Bone Junction in Male Rabbits with Dissimilar Femoral Defects / Evaluación Comparativa de la Osteogénesis de Contacto en la Unión entre el Hueso y el Implante de Titanio en Conejos Macho con Defectos Femorales Diferentes

SUMMARY: Traumatized bone tissue has the capacity to repair itself so that it eventually regains its almost original form, even in the case of artificially inserted implants. The process that stays at the base of the regeneration is represented by osteogenesis or remote osteogenesis. The major difference between the two types of bone formation is the location of the cement line, which is located on the surface of the implant for contact osteogenesis and on the surface of the bone defect for remote osteogenesis. The aim of the present study was to assess the contact osteogenesis in the case of inserted titanium screws in holes with diameters of 1.8 mm and 1 mm respectively. The obtained results show, in the case of the groove with 1.8 mm that the newly proliferated bone represents 73.85 % of the total area, while in the case of the groove with 1 mm in diameter the value of the newly proliferated bone is 26.15 %. In conclusion, the insertion of titanium screws by self-tapping into the hole smaller than the core of the screw is accompanied by bone proliferation by contact osteogenesis much more modest than in the case of insertion into the hole larger than the core of the screw.

El tejido óseo traumatizado tiene la capacidad de reparar en forma espontánea, de modo que eventualmente recupera su forma casi original, incluso en el caso de implantes insertados artificialmente. El proceso que queda en la base de la regeneración está representado por la osteogénesis u osteogénesis a distancia. La principal diferencia entre los dos tipos de formación ósea es la ubicación de la línea de cemento, que se encuentra en la superficie del implante para la osteogénesis de contacto y en la superficie del defecto óseo para la osteogénesis remota. El objetivo del presente estudio fue evaluar la osteogénesis de contacto en el caso de tornillos de titanio insertados en forámenes con diámetros de 1,8 mm y 1 mm respectivamente. Los resultados obtenidos muestran, en el caso del surco de 1,8 mm que el hueso neoproliferado representa el 73,85 % del área total, mientras que en el caso del surco de 1 mm de diámetro el valor del hueso neoproliferado es del 26,15 %. En conclusión, la inserción de tornillos de titanio por autorroscantes en el foramen menor que el núcleo del tornillo se acompaña de una proliferación ósea por osteogénesis de contacto mucho más modesta que en el caso de la inserción en el foramen mayor que el núcleo del tornillo.

Electrochemical Studies of Magnesium Coated with Modified Chitosan and Electrosprayed as an Anticorrosive Protection Method in Bone Repair / Estudios Electroquímicos del Magnesio Recubierto con Quitosano Modificado y Electrorociado como Proceso de Protección Anticorrosiva en la Reparación de Hueso

ABSTRACT Magnesium (Mg) is essential for the metabolic reactions of the human body and is known for its biocompatibility, its mechanical and physical properties are similar to human bone, which is why it is considered to have high potential in biomedical applications such as temporary and resorbable implants. Through surface modifications, the high tendency to corrosion of Mg could be controlled, such as biodegradable membranes that prevent the passage of chloride ions present in the human organism. To prepare the membrane, solutions of chitosan modified with gelatin and/or glutaraldehyde are used and by means of the electrospray method applied to protect the Mg. To simulate body fluid conditions a Kokubo saline solution (BFK) was prepared. The study focuses on evaluating the corrosion rate of Mg with a coating made of a chitosan electrosprayed membrane, applying electrochemical measurements of electrochemical impedance spectroscopy and linear polarization resistance. The key additive to improve the behavior of the membranes was observed with the use of gelatin, where the membrane with the best results lowing corrosion rates is the Mg CH+GE+GL system, which it was observed with very good physical integrity in the images of morphological analyzes of the surface after 30 days of exposure.

RESUMEN El magnesio (Mg) es esencial para las reacciones metabólicas del cuerpo humano y es conocido por su biocompatibilidad, sus propiedades mecánicas y físicas son similares a las del hueso humano, por lo que se considera que tiene un alto potencial en aplicaciones biomédicas como implantes temporales y reabsorbibles. Mediante modificaciones superficiales se podría controlar la alta tendencia a la corrosión del Mg, como por ejemplo membranas biodegradables que impidan el paso de iones cloruro presentes en el organismo humano. Para preparar la membrana se utilizan soluciones de quitosano modificado con grenetina y/o glutaraldehído y mediante el método de electrorociado se aplican para proteger el Mg. Para simular las condiciones de los fluidos corporales se preparó una solución salina de Kokubo. El estudio se enfoca en evaluar la velocidad de corrosión del Mg con un recubrimiento hecho de una membrana electrorociada con quitosano, aplicando técnicas electroquímicas de espectroscopia de impedancia electroquímica y resistencia de polarización lineal. El aditivo clave para mejorar el comportamiento de las membranas se observó con el uso de gelatina, donde la membrana con mejores resultados bajando los índices de corrosión es el sistema Mg CH+GR+GL, el cual se observó con muy buena integridad física en las imágenes de análisis morfológicos de la superficie después de 30 días de exposición.

Novel Studies in the Designs of Natural, Synthetic, and Compound Hydrogels with Biomedical Applications / Novedosos Estudios en el Diseño de Hidrogeles Naturales, Sintéticos y Compuestos con Aplicaciones Biomédicas

ABSTRACT Hydrogels are gaining widespread popularity in the biomedical field due to their extraordinary properties, such as biocompatibility, biodegradability, zero toxicity, easy processing, and similarity to physiological tissue. They have applications in controlled drug release, wound dressing, tissue engineering, and regenerative medicine. Among these applications, hydrogels as a controlled drug delivery system stands out, which releases active substances in precise amounts and at specific times. To explore the latest advances in the design of hydrogels, a literature review of articles published in indexed scientific journals, in Scopus and Science Direct, was carried out. This review aimed to discover and describe the most innovative hydrogel research with applications in the biomedical field; hydrogels synthesized with polymers of different origins were selected, such as; i. Natural (dextran, agarose, chitosan, etc.); ii. Synthetic (polyacrylamide, polyethylene glycol, polyvinyl alcohol, etc.); iii. Composites (interpenetrants, hybrid crosslinkers, nanocomposites, etc.). Comparative analysis revealed that hydrogels with composite materials show the most promise. These composite hydrogels combine the advantages of different polymers or incorporate additional components, offering enhanced properties and functionalities. In summary, hydrogels are versatile biomaterials with immense potential in biomedicine. Their unique properties make them suitable for diverse applications. However, innovative designs and formulations must continue to be explored to further advance the capabilities of hydrogels and expand their biomedical applications.

RESUMEN Los hidrogeles están ganando una extensa popularidad en el campo biomédico gracias a que presentan propiedades extraordinarias como biocompatibilidad, biodegradabilidad, nula toxicidad, fácil procesamiento, y similitud con el tejido fisiológico. tienen aplicaciones en la liberación controlada de fármacos, el vendaje de heridas, la ingeniería de tejidos y la medicina regenerativa. Entre estas aplicaciones, destaca el uso de hidrogeles como sistema de administración controlada de fármacos, que liberan sustancias activas en cantidades precisas y en momentos concretos. Para explorar los últimos avances en el diseño de hidrogeles, se realizó una revisión bibliográfica de artículos publicados en revistas científicas indexadas, en Scopus y Science Direct. El objetivo de esta revisión fue descubrir y describir las investigaciones de hidrogeles más innovadoras con aplicaciones en el campo biomédico, se seleccionaron hidrogeles sintetizados con polímeros de diferente índole como; i. Naturales (dextrano, agarosa, quitosano, etc.); ii. Sintéticos (poliacrilamida, polietilenglicol, alcohol polivinílico, etc); iii. Compuestos (interpenetrantes, reticulantes híbridos, nanocompuestos, etc.). El análisis comparativo reveló que los hidrogeles que utilizan materiales compuestos son los más prometedores. Estos hidrogeles compuestos combinan las ventajas de distintos polímeros o incorporan componentes adicionales, ofreciendo propiedades y funcionalidades mejoradas. En resumen, los hidrogeles son biomateriales versátiles con un inmenso potencial en biomedicina. Sus propiedades únicas los hacen adecuados para diversas aplicaciones, sin embargo, se debe seguir explorando diseños y formulaciones innovadores para seguir avanzando en las capacidades de los hidrogeles y ampliar sus aplicaciones biomédicas.

Beneficios de la reparación artroscópica del manguito rotador en octogenarios. Análisis de resultados funcionales y complicaciones / Benefits of arthroscopic rotator cuff repair in octogenar ians. Analysis of functional results and complications

Resumen Introducción: Existe falta de información en la litera tura sobre los resultados de la reparación artroscópica del manguito rotador en pacientes mayores de 80 años. El objetivo de este estudio fue evaluar una serie conse cutiva de pacientes con rupturas del manguito rotador a los que se les realizó la reparación artroscópica del mismo. Métodos: Análisis retrospectivo de pacientes mayores de 80 años a quienes se les realizó reparación artroscó pica de manguito rotador entre junio de 2004 y enero de 2016. El seguimiento mínimo fue de 2 años. Para la evaluación funcional y del dolor se utilizaron las escalas Constant, Dash, UCLA y Escala Visual Análoga (EVA). Resultados: El seguimiento promedio fue de 8.4 años. Se obtuvieron mejoras significativas en la valoración del rango de movilidad y la evaluación de las escalas de Constant, Dash y UCLA, y EVA. No se registraron complicaciones mayores y solo 4 pacientes requirieron una re-operación. Conclusión: Los principales hallazgos obtenidos fue ron la mejoría funcional y del dolor en los pacientes mayores de 80 años operados por una ruptura completa del manguito rotador en forma artroscópica.

Abstract Introduction: There is a lack of information in the literature on the results of arthroscopic rotator cuff re pair in patients older than 80 years. The purpose of this study was to evaluate a consecutive series of patients with rotator cuff tears who underwent arthroscopic rotator cuff repair. Methods: Retrospective analysis of patients older than 80 years who underwent arthroscopic rotator cuff repair between June 2004 and January 2016. The mini mum follow-up was 2 years. For functional and pain assessment, the Constant, Dash, UCLA scale and Visual Analogue Scale (VAS) for pain were used. Results: The average follow-up was 8.4 years. Signifi cant improvements were obtained in the assessment of the range of motion and the evaluation of the Constant, Dash and UCLA scales, as well as in the VAS. No major complications were recorded and only 4 patients re quired a reoperation. Conclusion: The main findings obtained were func tional and pain improvement in patients over 80 years of age operated on for a complete arthroscopic rotator cuff tear.

Injúria microbiana e a qualidade microbiológica dos alimentos / Microbial injury and the microbiological quality of food

Introdução: a contaminação microbiológica dos alimentos se apresenta como um grande problema para a indústria, agências reguladoras e consumidores. Os métodos de conservação utilizados como garantia da inocuidade dos alimentos bem como de extensão da vida de prateleira garantem uma redução significativa do número de células viáveis e/esporos. Entretanto, em virtude da aplicação de técnicas como calor, frio, redução da atividade de água e adição de conservantes, parte da população microbiana pode apresentar células com danos letais bem como danos reversíveis, tornando-se injuriadas. Objetivo: realizar uma revisão bibliográfica acerca da ocorrência de injúrias microbianas decorrentes da aplicação de métodos de conservação em alimentos. Metodologia: consulta das bases de dados Pubmed e Scielo, com seleção de artigos publicados entre os anos de 2000 e 2019. Revisão de literatura: os microrganismos se tornam injuriados após sobreviverem a condições estressantes e perderem parte de suas características funcionais, o que justifica um maior período para multiplicação nos alimentos, assim como em meios de cultura tradicionais. Cabe ressaltar que, caso estes microrganismos sejam expostos à ambientes favoráveis, é possível a recuperação dos danos sofridos. Uma vez regenerados, estes agentes representam um perigo potencial, visto a capacidade de se multiplicarem novamente no alimento, oferecendo riscos aos consumidores e acelerando a deterioração de produtos alimentícios. Conclusão: diante da ocorrência de injúrias microbianas, percebe-se a necessidade de incorporação de procedimentos adequados para recuperação de danos celulares aos métodos oficiais empregados para detecção e enumeração de microrganismos, a fim de garantir a qualidade e inocuidade de alimentos.

Introduction: Microbiological contamination of food is a major problem for industry, regulatory agencies and consumers. Preservation methods used to guarantee the safety of food as well as extending the shelf life ensure a significant reduction in the number of viable cells and/or spores. However, due to the application of techniques such as heat, cold, reduction of water activity and addition of preservatives, part of the microbial population may present cells with lethal damage as well as reversible damage, becoming injured. Objective: to carry out a literature review about the occurrence of microbial injuries resulting from the application of preservation methods in food. Methodology: pubmed and Scielo databases were consulted, with a selection of articles published between 2000 and 2019. Literature review: microorganisms become injured after surviving stressful conditions and losing part of their functional characteristics, which justifies a longer period for multiplication in food, as well as in traditional culture media. It should be noted that, if these microorganisms are exposed to favourable environments, it is possible to recover from the damage suffered. Once regenerated, these agents represent a potential hazard, given their ability to multiply again in food, posing risks to consumers and accelerating the deterioration of food products. Conclusion: in view of the occurrence of microbial injuries, it is necessary to incorporate adequate cell damage recovery procedures to the official methods used for detection and enumeration of microorganisms, in order to guarantee the quality and safety of food.