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1.
Br J Dermatol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230675

RESUMEN

BACKGROUND: A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. OBJECTIVE: We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. METHODS: This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. RESULTS: At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). CONCLUSIONS: There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

2.
J Multidiscip Healthc ; 17: 3743-3751, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104383

RESUMEN

Objective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life. Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status. Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p<0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05±12.28 vs 78.03±10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97±4.67 vs 36.2±3.36) and depression scale score (57.67±4.58 vs 38.71±3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05). Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38968045

RESUMEN

BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

4.
Arthrosc Tech ; 13(5): 102940, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38835472

RESUMEN

In anterior cruciate ligament (ACL) revision cases, the resultant bigger aperture at the tibia footprint can cause graft instability. The increased movement hinders bone-graft integration and leads to graft abrasion. This article describes a technique to optimize graft stability when using a soft tissue graft for ACL revision. The technique is used when there is suspicion of size mismatch between the new tibia footprint aperture and the graft. The first stage involves passing a suture via an anterolateral tibial tunnel connecting with the revision tibia tunnel distal to the tibia footprint aperture. The new graft is subsequently deployed, and the potential discrepancy between graft diameter and aperture is confirmed. The second stage involves placing 2 pulling sutures on the new graft and passing them into the anterolateral tibial tunnel. The tensioned and anchored pulling sutures secure graft stability at the tibia footprint, and the graft distal to that is fixed routinely. The lasso technique stabilizes the new graft at the tibia footprint by tensioning it in a distal and anterolateral direction. For selected cases, this technique enables a 1-stage ACL revision with a soft tissue graft when faced with graft instability at the tibia footprint.

5.
Ann Acad Med Singap ; 53(2): 113-116, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38920235

RESUMEN

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.


Asunto(s)
Queloide , Humanos , Queloide/terapia , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/tratamiento farmacológico , ARN/uso terapéutico , Dermatología/métodos , Enfermedades de la Piel/terapia , Enfermedades de la Piel/tratamiento farmacológico , Terapia Genética/métodos
6.
BMC Complement Med Ther ; 24(1): 194, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760722

RESUMEN

OBJECTIVE: To study the effect of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life in patients with sarcopenia receiving maintenance haemodialysis (MHD). METHODS: Eligible patients with sarcopenia in our hospital were randomly assigned to a control group (n = 24) and an intervention group (n = 25). The control group received conventional dialysis treatment, while the intervention group underwent mindfulness meditation combined with progressive muscle relaxation training during the interdialysis period in addition to conventional dialysis treatment. The effect of the intervention was evaluated after 12 weeks. RESULTS: There were no significant differences in the baseline values of various parameters between the two groups. Exercise capacity (sit-to-stand test,handgrip,time to 10 sit-ups) significantly improved in the intervention group after 12 weeks (32.68 ± 8.32 vs 26.50 ± 6.83; 37.42 ± 10.12 vs 28.12 ± 8.51; 19.8 ± 5.40 vs 25.29 ± 7.18) (p < 0.05). In terms of the kidney disease quality of life (KDQOLTM) score, all other dimensions except sexual function, social functioning, burden of kidney disease and work status dimensions showed significant improvement compared to the baseline (p < 0.05). In the control group, only the dialysis staff encouragement (DSE) and patient satisfaction (PS) dimensions showed slight improvements compared to the baseline (p > 0.05). When compared with the control group, the intervention group showed significant improvements in 10 dimensions of exercise capacity and KDQOLTM scores for physical function, role-physical, general health, energy, symptom/problem list, sleep, DSE, pain, cognitive function, emotional well-being and patient PS after 12 weeks (61.30 ± 5.38 vs 42.98 ± 5.73; 57.50 ± 3.55 vs 50.70 ± 3.62) (p < 0.05). Some inflammatory markers, such as the levels of interleukin-6 and high-sensitivity C-reactive protein (30.29 ± 2.96 vs 17.65 ± 3.22; 8.93 ± 0.99 vs 3.02 ± 0.34), showed a decrease during the intervention, while albumin and prealbumin levels were significantly increased compared with the baseline (30.62 ± 1.65 vs 35.60 ± 1.68; 0.32 ± 0.05 vs 0.44 ± 0.07) (p < 0.05). CONCLUSION: Combined intervention training can improve the motor ability and quality of life of patients with sarcopenia within a short period of time.


Asunto(s)
Meditación , Atención Plena , Calidad de Vida , Diálisis Renal , Sarcopenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Atención Plena/métodos , Anciano , Sarcopenia/terapia , Resultado del Tratamiento
7.
Curr Opin Nephrol Hypertens ; 33(4): 405-413, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573234

RESUMEN

PURPOSE OF REVIEW: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules. RECENT FINDINGS: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates. We applied EFA assays to freshly isolated mouse proximal tubules, thick ascending limbs (TALs), and distal convoluted tubules (DCTs) and successfully differentiated their unique metabolic features. We found that TALs and DCTs adjusted their mitochondrial bioenergetics and biogenesis in response to acute and chronic alterations of transport activity. Based on the literature and our recent findings, I discuss working models and mechanisms underlying acute and chronic tubular adaptations to transport activity. The potential roles of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) are discussed. SUMMARY: Mitochondria in renal tubules are highly plastic to accommodate different transport activities. Understanding the mechanisms may improve the treatment of renal tubulopathies.


Asunto(s)
Metabolismo Energético , Túbulos Renales , Mitocondrias , Animales , Mitocondrias/metabolismo , Humanos , Túbulos Renales/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Transporte Biológico
8.
J Orthop ; 54: 46-50, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38524364

RESUMEN

Background: Tourniquet use during total knee arthroplasty (TKA) reduces bleeding which optimises bone-cement interface for prosthesis stability and improves surgical field visualisation. However, prolonged usage can lead to complications and poorer outcomes. Some surgeons advocate for intermittent tourniquet application. Limited literature exists for patients with high body mass index (BMI). This study aims to compare the outcomes of intermittent tourniquet (IT) to throughout tourniquet (TT) use among obese patients undergoing primary TKA for knee osteoarthritis. Methods: This was a retrospective cohort study. In the TT group, tourniquet was inflated from the beginning and released once the bone cement has hardened. In the IT group, tourniquet was inflated at the beginning, released after initial incision and haemostasis, then inflated again during cementation. Tourniquet was released once the bone cement had set. Categorical outcome measures were analysed using Chi-squared or Fisher's exact test. T-test or Kruskal-Wallis test were used for continuous data. Results: When comparing IT to TT among patients with BMI≥30 (IT n = 48, TT n = 47), the mean duration of surgery was shorter in the TT group (p < 0.05). The difference in haemoglobin drop between the two groups was not statistically significant from post-operative day three onwards. There was no difference in transfusion rate (p > 0.05). ROM was greater in the IT group up to three weeks post-operatively (p < 0.05). When comparing patients with BMI <30 (n = 71) and BMI≥30 (n = 48) with IT use, there was no statistically significant difference in ROM and LOS. Conclusion: Patients with BMI≥30 in the IT group had greater ROM in the initial post-operative period. Although operative time and blood loss were greater among the IT group, there was no difference in transfusion rate. Outcomes of TKA performed with IT were similar for patients with BMI≥30 and BMI <30. The authors recommend intermittent tourniquet use during TKA for patients with BMI≥30. Level of evidence: 3.

9.
Protein Sci ; 33(3): e4904, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38358126

RESUMEN

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin-conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug-like small molecules. Here, we performed fragment screening using 19 F-nuclear magnetic resonance (NMR) and validated the hits with 1 H-15 N-heteronuclear single quantum coherence (HSQC) experiment and X-ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment-binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.


Asunto(s)
Enzimas Ubiquitina-Conjugadoras , Ubiquitina , Enzimas Ubiquitina-Conjugadoras/metabolismo , Sitios de Unión
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1022766

RESUMEN

Dry age-related macular degeneration(AMD)is a degenerative disease affecting the macular region of the retina,and aging changes in retinal and choroidal tissues are an important factor in AMD pathogenesis.Cell aging is an irre-versible state of cell cycle arrest triggered by certain physiological processes or stressful injury,affecting a variety of physi-ological and pathological processes.An increasing number of studies have shown that cell aging plays an essential role in the occurrence and development of AMD.This paper reviews the mechanisms of cell aging and its relationship with dry AMD,aiming to provide new ideas for the treatment of dry AMD.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1028618

RESUMEN

This article reports the diagnosis and treatment of a case of acromegaly in a pregnant patient who took bromocriptine during pregnancy and delivered successfully. A retrospective summary of the clinical data and treatment outcomes before and after two pregnancies of the patient is provided. The patient took bromocriptine during the second pregnancy, and her condition remained stable. A baby girl was delivered by caesarean section at full term. The article suggests that pregnancy in acromegaly patients, after the stabilization of the condition, can lead to favorable outcomes. The use of dopamine receptor agonists during pregnancy does not increase adverse events during the perinatal period.

12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1032149

RESUMEN

Objective @#Mendelian randomization analysis was used to explore the causal relationship of T.gondii in- fection and the cyst distribution and inflammation in brain tissue by immunohistochemistry.@*Methods @#Genome- wide association analysis data of T.gondii infection and encephalitis were obtained ,single nucleotide polymor- phisms (SNPs) were selected,Mendelian randomization analysis was conducted by inverse variance weighting,and the causal relationship between T.gondii infection and encephalitis was evaluated by OR value and 95% CI.Quality control was carried out by using heterogeneity test,horizontal multi-efficiency test and leave-one-out sensitivity test. Immunohistochemical staining was performed using brain sections of mice infected with tissue cysts of Wh6 strain for image analysis using Image J software. @*Results @#A total of 29 SNPs were associated with toxoplasmic encephalitis. The results of IVW method suggested that T.gondii infection made encephalitis risk 0. 98 times higher ( OR = 0. 98, 95% CI = 0. 76 to 1. 27) ,indicating no causal relationship between the two.The quality control results suggested that the selected SNPs were stable and reliable.Toxoplasma cysts were distributed in various parts of the brain tis- sue.@*Conclusion @# T.gondii infection and encephalitis are related,but there is no sufficient evidence to prove the causal relationship between the two.

13.
Ann Phys Rehabil Med ; 67(2): 101790, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38118296

RESUMEN

BACKGROUND: Evidence for the association between acceptance of disability (AOD) and positive rehabilitation outcomes, as well as for the use of AOD measurements in stroke rehabilitation practice, has increased in the international literature in the last decade. However, measurement tools for AOD are heterogenous and there has not been a systematic review summarizing the current evidence on the use of AOD measures and factors associated with AOD. OBJECTIVE: This study aimed to summarize current evidence on measurement tools used, present existing AOD scores in people with stroke and identify risk factors for and protective factors against poor AOD in people with stroke. METHODS: The original design and protocol of this systematic review were registered with PROSPERO. The included studies were published from 2008 to 2020 and identified from 5 databases-PubMed, EMBASE, CINAHL Plus, PsycInfo, and the Cochrane Library-using the following inclusion criteria: participants diagnosed with stroke and aged ≥16 years, measurement of AOD, and published in English in a peer-reviewed scientific journal. Review articles were excluded. RESULTS: Five measurement tools for AOD were reported. The Revised Acceptance of Disability Scale (ADS-R) and the acceptance subscale of the Illness Cognition Questionnaire (ICQ) had the highest internal consistency. Scores ranged from 71.7 to 74.2 on the ADS-R, 16.9-18.3 on the ICQ, 16.5-26.9 on the Acceptance of Illness Scale, and 87.8-93.2 on the Attitudes towards Disabled Persons Form A. Poorer function and depressive symptoms were associated with poor AOD, whereas religious beliefs, support from others, and an understanding of stroke were associated with better AOD. CONCLUSIONS: The ADS-R and the acceptance subscale of the ICQ are currently the most reliable measurement tools for measuring AOD in people with stroke. Further research to validate the measurement tools is required. This may help to identify people who require additional support. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42017077063; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=77063.


Asunto(s)
Evaluación de la Discapacidad , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/psicología , Personas con Discapacidad/rehabilitación , Personas con Discapacidad/psicología , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/complicaciones , Encuestas y Cuestionarios , Femenino , Masculino , Persona de Mediana Edad
14.
Cureus ; 15(10): e46629, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37937016

RESUMEN

Introduction Open reduction internal fixation (ORIF) and primary arthrodesis are two conventional options for the treatment of Lisfranc injuries. However, they are associated with implant-related complications. An alternative suspensory device construct using interosseous nonabsorbable sutures with endobuttons has been described with satisfactory results. This study aims to explore functional outcomes after suture button fixation of Lisfranc injuries in a Southeast Asian population. Methods This was a single-surgeon retrospective study of patients with Lisfranc injuries treated surgically using a suture button fixation technique between 2017 and 2019. Data collected included demographic information, pre-injury levels of activity, nature of injury, and type of surgery performed. The minimum postoperative follow-up was one year. The Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM) were used to evaluate patient-reported outcomes. Scores were reported in percentage (%) with median and interquartile range. Results Twenty-nine patients with a mean age of 29 years (21-76) were recruited. Sixteen underwent suture button fixation only (SB), and 13 underwent suture button fixation with intercuneiform screw fixation and plating (SBM). The median scores for the FAOS and FAAM questionnaires were at least 80% in all domains. Twenty-eight patients (97%) were able to return to pre-injury activity level, 27 patients (93%) were able to return to sports. Only one patient was not satisfied with the outcomes of surgery. No patients had post-traumatic arthritis or hardware failure necessitating implant removal at the final follow-up. Conclusion This study has demonstrated that treatment of Lisfranc injuries with a suspensory device construct resulted in good outcomes with 97% of patients being able to return to pre-injury activity levels, and 93% of patients being able to return to sports. It may not be necessary to perform primary arthrodesis in uncomplicated Lisfranc injuries. This technique is also advantageous as implant removal is not routinely required due to the design and biomechanical properties of suspensory devices.

15.
Biomol NMR Assign ; 17(2): 269-274, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37773242

RESUMEN

Ubiquitin-conjugating enzyme E2 T (UBE2T) plays important roles in ubiquitination of proteins through participation in transferring ubiquitin to its substrate. Due to its importance in protein modifications, UBE2T associates with diverse diseases and serves as an important target for drug discovery and development. The crystal structure of UBE2T has been determined and the structure reveals the lack of a druggable pocket for binding to small molecules for clinical applications. Despite the challenge, effort has been made to develop UBE2T inhibitors. We obtained UBE2T constructs with and without the C-terminal region which is flexible in solution. Herein, we report the backbone resonance assignments for human UBE2T without the C-terminal region. The backbone dynamics of UBE2T was also explored. The available assignments will be helpful for hit identification, determining ligand binding site and understanding the mechanism of action of UBE2T inhibitors.


Asunto(s)
Enzimas Ubiquitina-Conjugadoras , Ubiquitina , Humanos , Resonancia Magnética Nuclear Biomolecular , Ubiquitinación , Ubiquitina/metabolismo
16.
Small ; 19(37): e2302332, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37140106

RESUMEN

Stacking order plays a key role in defining the electrochemical behavior and structural stability of layer-structured cathode materials. However, the detailed effects of stacking order on anionic redox in layer-structured cathode materials have not been investigated specifically and are still unrevealed. Herein, two layered cathodes with the same chemical formula but different stacking orders: P2-Na0.75 Li0.2 Mn0.7 Cu0.1 O2 (P2-LMC) and P3-Na0.75 Li0.2 Mn0.7 Cu0.1 O2 (P3-LMC) are compared. It is found that P3 stacking order is beneficial to improve the oxygen redox reversibility compared with P2 stacking order. By using synchrotron hard and soft X-ray absorption spectroscopies, three redox couples of Cu2+ /Cu3+ , Mn3.5+ /Mn4+ , and O2- /O- are revealed to contribute charge compensation in P3 structure simultaneously, and two redox couples of Cu2+ /Cu3+ and O2- /O- are more reversible than those in P2-LMC due to the higher electronic densities in Cu 3d and O 2p orbitals in P3-LMC. In situ X-ray diffraction reveals that P3-LMC exhibits higher structural reversibility during charge and discharge than P2-LMC, even at 5C rate. As a result, P3-LMC delivers a high reversible capacity of 190.3 mAh g-1 and capacity retention of 125.7 mAh g-1 over 100 cycles. These findings provide new insight into oxygen-redox-involved layered cathode materials for SIBs.

17.
Br J Ophthalmol ; 107(6): 889-894, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-34670748

RESUMEN

BACKGROUND: Scleral cross-linking is a potential method to inhibit axial elongation of the eye, preventing the progression of pathological myopia. Formaldehyde releasers, which are common preservatives found in cosmetics and ophthalmic solutions, have been shown to be not only effective in cross-linking corneal collagen in vitro and in vivo, but also have minimal toxicity effects on the eye. The present study aims to evaluate the efficacy of scleral cross-linking using sodium hydroxymethylglycinate (SMG) to inhibit eye growth using an in vivo rabbit model. METHODS: A cross-linking solution containing 40 mM SMG was delivered to the sub-Tenon's space behind the equator. The application regimen included a two-quadrant injection performed five times over 2 weeks on New Zealand White rabbits (n=5, group 1), and one-time injection followed for up to 5 days on Dutch-Belted rabbits (n=6, group 2). Group 1 was monitored serially for axial length changes using B-scan ultrasound for 5-6 weeks. Group 2 was injected with a higher viscosity solution formulation. Both groups were evaluated for thermal denaturation temperature changes of the sclera postmortem. RESULTS: Axial growth was limited by 10%-20% following SMG treatment as compared with the untreated eye. Thermal denaturation analysis showed increased heat resistance of the treated eyes in the areas of injection. Overall, the SMG treatment inhibited eye growth with few side effects from the injections. CONCLUSIONS: Cross-linking solutions delivered via sub-Tenon injection provide a potential method for limiting axial length growth in progressive myopia and could be used as a potential treatment for myopia.


Asunto(s)
Miopía Degenerativa , Esclerótica , Conejos , Animales , Reactivos de Enlaces Cruzados/farmacología , Modelos Animales de Enfermedad , Inyecciones
18.
Hum Mol Genet ; 32(2): 204-217, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-35943778

RESUMEN

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.


Asunto(s)
Degeneración Macular , Drusas del Disco Óptico , Masculino , Ratones , Femenino , Animales , Factor B del Complemento/genética , Degeneración Macular/genética , Degeneración Macular/patología , Drusas del Disco Óptico/patología , Retina/patología , Epitelio Pigmentado de la Retina/patología
19.
Journal of Clinical Hepatology ; (12): 936-940, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-971855

RESUMEN

Portal pressure measurement plays an important role in the diagnosis and evaluation of portal hypertension, and at present, there is still no unified method for the assessment of portal vein pressure. With the wide application of endoscopic ultrasound in digestive system diseases, endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement was included in the research agenda of the 2021 Baveno-VII conference, thus attracting widespread attention of scholars. This article reviews portal pressure measurement techniques, the development of EUS-PPG measurement technique, and two commonly used methods for EUS-PPG measurement in China and globally and elaborates on the application prospect of EUS-PPG measurement technique. A number of studies around the world have shown that EUS-PPG measurement technique is a direct, minimally invasive, simple, accurate, and radiation-free technique with strong clinical operability, and it is an important supplement to portal pressure measurement methods and may gradually become one of the main methods for portal pressure measurement.

20.
JOURNAL OF RARE DISEASES ; (4): 359-364, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1004963

RESUMEN

A middle-aged man was presented with poor appetite, polyuria, polydrpsia, and headache. A sellar mass was found, along with total pituitary hypofunction and visual field defect. A biopsy of the lesion via the trans-sphenoidal approach showed inflammatory changes and granuloma formation. However, repeated cerebrospinal fluid and pathogenic examination of the pathological tissue showed no positive indications. The initial diagnosis considered autoimmune hypophysitis, and treatment of glucocorticoids combined with immunosuppressants was administered, which led to a temporary shrinkage of the lesion, but it gradually enlarged subsequently. After multidisciplinary discussion, a high possibility of pituitary tuberculosis infection was decided upon. After standardized anti-tuberculosis treatment was initiated, the lesion reduced noticeably and the patient′s condition improved. Pituitary tuberculosis infection is incredibly rare and extremely easy to misdiagnose. This case was diagnosed and treated in a timely and effective manner through a multidisciplinary approach, highlighting the importance of such an approach in dealing with rare diseases.

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