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1.
Dermatol Surg ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900089

RESUMEN

BACKGROUND: The superior auricular artery (SAA)-retroauricular flap is commonly used for the repair of defects of the superior auricle. There are few studies about the anatomy of the SAA. OBJECTIVE: This study mainly analyzed the anatomical pattern of SAA. MATERIALS AND METHODS: Computed tomography (CT) was performed on 26 cadaver heads infused with lead oxide. The anatomical pattern of the SAA was statistically analyzed by 3-dimensional CT images. RESULTS: The SAA was classified into 3 types according to whether it gave off the helix branch or the auricular dorsal branch. The SAA was located mainly in an area 2 cm above and below the horizontal line at the midpoint of the 2 base points (the otobasion superius and the apex of the external auditory canal). The origin of each branch of the SAA was mainly located in Areas 2, 3, and 4 within a circular area that had the otobasion superius as the center of the circle and a radius of 2 cm. CONCLUSION: In this study, the 3 anatomical types and anatomical patterns of the SAA were identified. These findings can provide a reference for the design of SAA-retroauricular flaps and for surgical planning.

2.
Iran J Public Health ; 53(3): 614-624, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38919288

RESUMEN

Background: Fine particulate matter (PM2.5), an important component of ambient air pollution, induces significant adverse health effects. MitoQuinone (MitoQ), a mitochondria-targeted antioxidant, has been reported to play a protective role in various diseases. However, the roles of MitoQ in PM2.5 induced pulmonary toxicity remains to be elucidated. Methods: All the experiments were performed at Higher Educational Key Laboratory for Translational Oncology of Fujian Province, Putian City, China in 2023. Pulmonary epithelial cells (A549) were pretreated with 4 µM MitoQ for 2 h and exposed to PM2.5 for 24 h. Cell viability was tested through CCK8 assay. Oxidative stress state and active mitochondria was used to study MitoQ's effect on PM2.5 induced injury, and cell apoptosis was measured using a flow cytometer and analyzed by Bcl-2 family. Results: MitoQ pretreatment significantly relieved a decreased cell viability, subsequently, MitoQ alleviated ROS production and prevented the reduction of T-AOC and GSH and increased the expression of NF-E2-related factor 2 (Nrf2) and p62 in A549 cells exposed to PM2.5. MitoQ restored the decreased mitochondrial dysfunction and dynamics disorder and inhibited activated mitochondrial-mediated apoptosis induced by PM2.5. Furthermore, the decreased ratio of Bcl-2/Bax and expression of Mcl-1 and the enhanced expression of Caspase-3 were reversed by MitoQ pretreatment. Conclusion: MitoQ might be regarded as a potential drug to relieve PM2.5 induced pulmonary epithelial cells damage.

3.
Aesthetic Plast Surg ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839616

RESUMEN

BACKGROUND: As a facial feature, the auricle plays an important role in the integrity and aesthetics of the whole face. Auricular subunits are associated with patient satisfaction in auricular reconstruction, but there are few studies on auricular subunits. We want to evaluate the reproducibility of auricular subunits by measuring the coordinates of the marker points of auricular subunits, accordingly provide a reference for the improvement of auricular reconstruction and the aesthetics of auricular injection. METHODS: Mimics 19.0 was used to carry out three-dimensional (3D) reconstruction of the computed tomography (CT) scan data of patients' brains; measure the three-dimensional coordinates of the 13 auricular subunit markers, the morphological auricle length and width, and the physiological auricle length and width; and analyze the reproducibility as well as the differences between group. RESULTS: Reproducibility of auricle subunit markers: There are 1124 (58.82%) high reproducibility, 580 (30.35%) moderate reproducibility, and 207 (10.83%) low reproducibility. The superior tragus notch, tragus, and antitragus had the highest reproducibility. There was no significant difference between the groups in the marking points on the helix, and there were no statistically significant differences in the measurement values of the auricles on the two sides. The physiological ear length and width and the morphological ear length of males were larger than those of females. These showed significant differences between the age groups. CONCLUSION: Most auricular subunit markers have high reproducibility. The subunits with higher reproducibility are the structures that need to be optimized during auricle reconstruction surgery or auricle injection in the future. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

4.
Aesthetic Plast Surg ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565722

RESUMEN

BACKGROUND: Ears are an important aesthetic feature that is vital to the overall attractiveness of the face. Although there have been many studies on the aesthetics of the auricle, there is currently a lack of consensus on the ideal proportion of auricle exposure for Asian women in frontal view. OBJECTIVES: This study aimed to investigate ideal proportion of auricle exposure in Asian women. METHODS: An observational study was carried out on the photographs of 84 women on the list of the 100 most beautiful faces in Asia (published by TCC Asia in 2020). The proportion of the distance between the outer canthus and the outermost point of auricle to the distance between the inner canthus and the outermost point of auricle was calculated as the auricle exposure proportion. Evaluators were asked to rank a set of photographs of the volunteer with varying auricle exposure proportions from most attractive to least attractive. RESULTS: Measurements of the photographs of the 84 women showed a mean ear exposure proportion of 0.600. With 487 questionnaire responses received, the proportion of auricle exposure that the evaluators considered most attractive was 0.600. People with aesthetic experience considered 0.625 the most attractive proportion, while the general group considered 0.600 the most attractive. CONCLUSIONS: The ideal proportion of the auricle exposure for Asian women is in the range of 0.60-0.625, which may help surgeons reconstruct aesthetically pleasing ears. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

5.
FASEB J ; 38(8): e23613, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38661048

RESUMEN

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.


Asunto(s)
Tejido Adiposo , Macrófagos , PPAR gamma , Rosiglitazona , Trasplante Autólogo , Animales , PPAR gamma/metabolismo , PPAR gamma/genética , Macrófagos/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/citología , Rosiglitazona/farmacología , Masculino , Diferenciación Celular , Adipogénesis , Adipocitos/metabolismo , Ratones , Ratas
6.
Plast Reconstr Surg Glob Open ; 12(2): e5579, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38313594

RESUMEN

Background: The demand for soft tissue filler injections has experienced a significant increase in recent years. Therefore, this study used bibliometric analysis to identify prominent research areas and emerging trends within the field. Methods: Publications concerning research on soft tissue filler injections were collected from the Web of Science Core Collection database. Subsequently, VOSviewer 1.6.18 and CiteSpace 6.2.R4 software were used to analyze the co-authorship, co-occurrence, and citations of countries, institutions, authors, hotspot keywords, and journals associated with these studies. Results: A total of 1370 records pertaining to filler injection research conducted between 2000 and 2022 were identified. The United States (524 publications) emerged as the country with the highest number of publications in this field, with Mayo Clinic (37 publications) making the most substantial contribution. Dermatologic Surgery emerged as the leading journal in this field, publishing the highest number of research articles (151 publications) and also being the most frequently co-cited. Cotofana proved to be the most prolific author with 51 publications, and Lemperle emerged as the most frequently co-cited author with 628 citations (including total link strength: 6587). The most popular keywords, in descending order of popularity, were "dermal filler," "injection," "soft-tissue augmentation," "complications," and "hyaluronic acid." Conclusions: The findings of this study offer a comprehensive overview of the main directions in filler injection research. Furthermore, they underscore the imperative of intensifying efforts to prevent complications linked to filler injections.

7.
Aesthetic Plast Surg ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388798

RESUMEN

Ophthalmic artery occlusion caused by facial hyaluronic acid filler injection has always been a rare but devastating complication. With the pursuit of beauty, people have become more interested in ears and hyaluronic acid fillers. Herein, we report the case of a more serious rare complication of ophthalmic artery occlusion caused by ear filler injection. A 45-year-old woman developed vision loss on the left side immediately after receiving cosmetic hyaluronic acid injection in the ear, with only the visual field at the inferior temporal side remaining. She was diagnosed with central retinal artery occlusion in the left eye. After treatment with hyaluronidase injection, dexamethasone, hyperbaric oxygen, and oral alprostadil, blood flow was partially restored in the left ophthalmic artery, and her vision improved. Vascular complications after ear injections are rare. However, as the demand for ear filler injections increases, the probability of serious vascular complications is predicted to increase. The potential mechanism by which occlusion occurred involved the filler reaching the superficial temporal artery system through the superior auricular artery, thus occluding the ophthalmic artery. Having an understanding of anatomy is an important measure to avoid complications.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

8.
Plast Reconstr Surg ; 153(1): 74e-78e, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36988631

RESUMEN

SUMMARY: Lying-ear deformity refers to an auricle that bends backward excessively, is excessively folded against the head, and has a very prominent antihelix. It usually requires experienced surgeons to perform surgical treatment and a prolonged postoperative recovery process. This article proposes a simple and effective hyaluronic acid injection technique that significantly improves the shape of the outer ear and enhances perceived facial aesthetics. Twenty patients underwent treatment with multiple injections. Measure-related parameters were used to evaluate the postoperative effect, and the results were graded using a visual analog scale. Interrater reliability among graders was evaluated using intraclass correlation coefficients. After treatment, no serious complications, such as infection or embolism, occurred. Six months after the procedure, the average auriculocephalic angle increased from 25.11 ± 9.46 to 32.72 ± 8.29 degrees, the average conchoscaphal angle increased from 87.69 ± 9.06 to 95.94 ± 7.11 degrees, and patients' average visual analog scale score increased from 4.40 ± 1.14 to 8.57 ± 0.68. Interrater reliability was fair to good for visual analog scale before injection and 6 months after injection (intraclass correlation coefficients, 0.49 and 0.45, respectively; both P < 0.001). The patients were satisfied with the injection process and results. This injection protocol improved the shape of the outer ear, resulting in excellent postoperative outcomes.


Asunto(s)
Pabellón Auricular , Procedimientos de Cirugía Plástica , Humanos , Reproducibilidad de los Resultados , Oído Externo/cirugía , Pabellón Auricular/cirugía , Trasplante de Piel , Resultado del Tratamiento
9.
Cancers (Basel) ; 15(24)2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38136320

RESUMEN

At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.

11.
J Chromatogr A ; 1707: 464292, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37586302

RESUMEN

The multicolumn counter-current solvent gradient purification (MCSGP) method has proven effective in addressing the issue of elution profile overlap for difficult-to-separate proteins, leading to improved purity and recovery. However, during the MCSGP process, the flow rate and proportion of loaded proteins undergo changes, causing a significant discrepancy between the elution profiles of batch process design and the actual MCSGP process. This mismatch negatively impacts the purity and recovery of the target protein. To address this challenge, an improved process design (reDesign) was proposed with the first-run MCSGP to mimic the actual continuous process and obtain elution profiles that closely resemble the real ones. The reDesign was demonstrated with both a model protein mixture and a sample of monoclonal antibody (mAb) with charge variants. For model protein mixture, the reDesign-based MCSGP process (reMCSGP) showed a remarkable improvement in recovery, increasing from 83.6% to 97.8% while maintaining a purity of more than 95%. For mAb sample, the recovery of reMCSGP improved significantly to 93.9%, surpassing the performance of normal MCSGP processes at a given purity level of more than 84%. In general, the new process design strategy developed in this work could generate a more representative elution profile that closely mirrors actual conditions in continuous processes, which enhances the separation performance of MCSGP.


Asunto(s)
Anticuerpos Monoclonales , Solventes
12.
3 Biotech ; 13(8): 283, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37501919

RESUMEN

Neutralizing monoclonal antibodies (nMABs) have been proved to be effective therapeutics in treating coronavirus disease (COVID-19). To enhance the potency of nMAB 553-15, we generated a novel monospecific tetravalent IgG1-(scFv)2 version. This was achieved by covalently fusing two forms of 553-15-derived single chain variable fragments (scFv) to the C-terminus of the hIgG1 (human Immunoglobulin G1) Fc fragment. We found that the Fc-fused VL-linker-VH format achieved similar binding affinity and neutralizing behavior as 553-15. The tetravalent versions were constructed by fusing the scFv domains to the C-terminus of nMAB 553-15. As a result, the tetravalent version 55,315-VLVH exhibited significantly higher binding activity to target spike protein variants and enhanced neutralization against VOCs (variants of concern) pseudovirus compared to 553-15. We also measured the Fc effector responses of candidates using wild-type Spike-expressing CHOK1 cells. The 55,315-VLVH enhanced the function of ADCP (antibody-dependent cellular phagocytosis) but had similar IL-6 release levels compared to the bivalent 553-15. It seemed that the novel tetravalent version avoids the pro-inflammatory effect induced by macrophage activation. However, the 55,315-VLVH displayed slightly increased potency in ADCC (antibody-dependent cell-mediated cytotoxicity) and CDC (complement-dependent cytotoxicity), which might contribute to higher systemic inflammation. Further investigation is necessary to determine whether the tetravalent version is beneficial to balance efficiency and safety against COVID-19.

13.
Aesthetic Plast Surg ; 47(5): 2117-2129, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37400586

RESUMEN

BACKGROUND: Cryopreserved fat has limited clinical applications due to its rapid absorption, high degree of fibrosis, and risk of complications after grafting. Many studies have verified that Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) can improve fresh fat graft survival. This study assessed whether ADSC-Exos could improve the survival of cryopreserved fat grafts. METHODS: Exosomes were isolated from human ADSCs were subcutaneously engrafted with adipose tissues stored under different conditions (fresh; cryopreserved for 1 month) into the backs of BALB/c nude mice (n = 24), and exosomes or PBS were administered weekly. Grafts were harvested at 1, 2, 4, and 8 weeks, and fat retention rate, histologic, and immunohistochemical analyses were conducted. RESULTS: At 1, 2, and 4 weeks after the transfer, cryopreserved fat grafts in groups of exosome-treated showed better fat integrity, fewer oil cysts, and reduced fibrosis. Further investigations of macrophage infiltration and neovascularization revealed that those exosomes increased the number of M2 macrophages at 2 and 4 weeks (p<0.05), but had limited impact on vascularization (p>0.05). It's important to note that no significant differences (p>0.05) were observed between the two groups in both histological and immunohistochemical evaluations at 8 weeks post-transplantation. CONCLUSIONS: This study suggests that ADSC-Exos could improve the survival of cryopreserved fat grafts in the short term (within 4 weeks), but the overall improvement was poor (after 8 weeks). This suggests that the utility of using ADSC-Exos to treat cryopreserved adipose tissue grafts is limited. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Exosomas , Supervivencia de Injerto , Ratones , Animales , Humanos , Exosomas/trasplante , Ratones Desnudos , Tejido Adiposo/trasplante , Criopreservación , Células Madre , Fibrosis
14.
Medicine (Baltimore) ; 102(28): e34333, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37443507

RESUMEN

RATIONALE: To investigate the clinical efficacy of the axillary approach in the surgical treatment of Ideberg type I and II scapular glenoid fractures. PATIENT CONCERNS AND DIAGNOSIS: Retrospective analysis of 13 cases of scapular glenoid fracture treated in the affiliated Hospital of Jining Medical College, Jiaxiang County People hospital, Zoucheng City people Hospital, Yanzhou District People Hospital, and Juancheng County people Hospital from December 2020 to January 2022. Eight males (including 1 bilateral) and 5 females, with an average age of 57.5 years (range from 33 to 75 years). According to Ideberg classification, there were 10 cases of type I a, 1 case of type I a combined with type I b, and 2 cases of type II. All patients were treated with axillary approach surgery and 7 patients with combined anterior shoulder dislocation were treated by first-stage manipulation and second-stage reoperation. Seven patients were fixed with a wire anchor, 3 patients with type I a were fixed with a "T" plate, and 5 patients were complicated with rotator cuff tear and were repaired with a wire anchor. At the last follow-up, the Constant-Murley shoulder function score, visual analog score, DASH score, and Hawkins grade were used to evaluate shoulder function, pain, and stability after treatment. INTERVENTION: The intervention was to treat patients with Ideberg type I and II scaphoid fractures using an axillary approach. OUTCOMES: All 13 patients in this group were followed up thoroughly, and the follow-up time was 12 to 25 months, with an average of 18.6 months. The operation time was 65 to 135 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 to 120 mL, averaging 55.6 mL. The duration of hospitalization ranged from 7 to 22 days, with an average of 9.6 days. The surgical incisions of all patients were grade-A healing. Bone healing of glenoid fractures was observed 3 months after the operation. LESSONS: The axillary approach for Ideberg type I and II scapular glenoid fractures is a feasible surgical approach with complete access through the muscle gap, minimal surgical trauma, mild postoperative pain, and satisfactory clinical results.


Asunto(s)
Fijación Interna de Fracturas , Fracturas del Hombro , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Escápula/cirugía , Escápula/lesiones , Hombro/cirugía , Fracturas del Hombro/cirugía , Resultado del Tratamiento
15.
Aesthetic Plast Surg ; 47(5): 2045-2050, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37076704

RESUMEN

BACKGROUND: Knowledge of the anatomy of the deep temporal artery (DTA) is critical to ensure safe filling of the deep temporal region. However, current treatment guidelines still focus on how to avoid the superficial temporal artery and the middle temporal vein, and an understanding of the safety of avoiding DTA injury is lacking. OBJECTIVE: The purpose of this study was to determine the positioning and course of the DTA to help clinicians safely perform the injection and filling in the temporal region. METHODS: Computed tomography (CT) scans and dissections of the skulls of 34 fresh frozen cadavers perfused with lead oxide were performed. Reconstruction and trajectory analysis of all DTA branches were performed using Mimics and MATLAB software. RESULTS: In this study, the DTA was identified in all samples, which originated from the maxillary artery of the external carotid artery system. According to image reconstruction and anatomical observations, the distribution of the anterior and posterior branches of the DTA had two different distribution patterns. The anatomical level of the DTA is located between the temporal muscle and the periosteal layer. Compared with observations in previous studies, the anterior branch of the DTA is slightly different, and we found that its course is closer to the frontal area in Asian specimens. CONCLUSION: The anatomical information on the DTA described in this study may help improve awareness of the safety of temporal injection by aesthetic physicians. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266. .


Asunto(s)
Disección , Arterias Temporales , Humanos , Arterias Temporales/diagnóstico por imagen , Inyecciones , Cadáver
16.
Plast Reconstr Surg ; 151(6): 1180-1185, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728786

RESUMEN

BACKGROUND: The current anatomical description of the zygomatico-orbital artery (ZOA) is mainly based on cadaver head studies and does not accurately reflect the complete anatomical information of the ZOA. The purpose of this study was to reveal the anatomical characteristics of the ZOA and to provide an anatomical basis for relevant operations in the temporal area. METHODS: Computed tomographic scans and autopsies were performed on 78 cadaver heads perfused with lead oxide. Mimics software was used to construct a three-dimensional image based on the bilateral intertragic notches and the right inferior orbital margin for a detailed analysis of the ZOA. RESULTS: The occurrence rate of ZOA in the 101 qualified hemisectioned cadaver heads was 86.14% (87 of 101). According to our observations, 46 of 87 (52.87%) originated from the superficial temporal artery above the zygomatic arch, 23 of 87 (26.44%) from the superficial temporal artery under the zygomatic arch, and 18 of 87 (20.69%) from the frontal branch of the superficial temporal artery. The ZOA communicates with the deep and superficial arches of the supraorbital artery, transverse facial artery, and ophthalmic artery. CONCLUSIONS: This study describes the anatomical characteristics of the ZOA. Moreover, these findings may guide skin flap transplantation and prevent associated injection complications.


Asunto(s)
Cabeza , Cigoma , Humanos , Cigoma/diagnóstico por imagen , Cigoma/irrigación sanguínea , Colgajos Quirúrgicos , Arteria Oftálmica/diagnóstico por imagen , Cadáver , Arterias Temporales/diagnóstico por imagen
17.
Cancers (Basel) ; 14(19)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36230887

RESUMEN

Immune checkpoint inhibitors (ICIs) are remarkable breakthroughs in treating various types of cancer, but many patients still do not derive long-term clinical benefits. Increasing evidence shows that TGF-ß can promote cancer progression and confer resistance to ICI therapies. Consequently, dual blocking of TGF-ß and immune checkpoint may provide an effective approach to enhance the effectiveness of ICI therapies. Here, we reported the development and preclinical characterization of a novel bifunctional anti-PD-L1/TGF-ß fusion protein, BR102. BR102 comprises an anti-PD-L1 antibody fused to the extracellular domain (ECD) of human TGF-ßRII. BR102 is capable of simultaneously binding to TGF-ß and PD-L1. Incorporating TGF-ßRII into BR102 does not alter the PD-L1 blocking activity of BR102. In vitro characterization further demonstrated that BR102 could disrupt TGF-ß-induced signaling. Moreover, BR102 significantly inhibits tumor growth in vivo and exerts a superior antitumor effect compared to anti-PD-L1. Administration of BR102 to cynomolgus monkeys is well-tolerated, with only minimal to moderate and reversing red cell changes noted. The data demonstrated the efficacy and safety of the novel anti-PD-L1/TGF-ß fusion protein and supported the further clinical development of BR102 for anticancer therapy.

18.
Medicine (Baltimore) ; 101(33): e30149, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-35984144

RESUMEN

RATIONALE: To evaluate the clinical effects of 1-stage revascularization, vacuum sealing drainage covering the wound, temporary external fixation and 2-stage Ilizarov bone transport for the treatment limb destruction injury. PATIENT CONCERNS AND DIAGNOSIS: Nine patients with limb destruction injury between September 2014 and June 2019 at our institute were evaluated retrospectively. The age of patient was 21 to 51 years with an average of 33 years. The injuries were caused by vehicle accidents in 4 patients, gunshot in 1 patient, and crushing injuries in 4 patients. All of them had vascular injury. The average length of bone defect was 9.5 (8.3-10) cm. Regular follow-up was performed on wound healing, bone transport time, bone healing time, external fixation index, and limb function. INTERVENTIONS: All patients underwent 1-stage revascularization and temporary external fixation during emergency surgery, and then gradual bone transport by Ilizarov fixator was performed until the broken fracture site was reunited. OUTCOMES: Nine patients were followed up for 12 to 48 months (average 30 months). Six patients were treated with autogenous cancellous bone graft for the second time, and 2 patients healed spontaneously. The mean wound healing time was 86 (73-90) days. The bone transport time was 97 (88.3-105.3) days, and the bone mineralization time was 164.5 (156.8-181.3) days, and the healing time of the docking sites was 6.8 (6.1-8.3) months. The external fixator time was 14.5 (12.5-17) months with the external fixation index was 1.5 (1.4-1.8) m/cm. At the last follow-up, according to the Association for the Study of the Method of Ilizarov functional scores, excellent functional outcomes were obtained in 5 patients, good in 1 patients, moderate in 2 patients. According to the Association for the Study of the Method of Ilizarov Radiological System, excellent functional outcomes were obtained in 6 cases and good in 2 cases. LESSONS: One-stage revascularization and temporary external fixation combined with 2-stage Ilizarov bone transport technique for the treatment of bone defects in limb destruction injury have satisfactory clinical effects and few complications, and can be applied under the condition of strict understanding of surgical indications.


Asunto(s)
Técnica de Ilizarov , Fracturas de la Tibia , Adulto , Fijadores Externos , Humanos , Extremidad Inferior , Persona de Mediana Edad , Estudios Retrospectivos , Tibia/cirugía , Fracturas de la Tibia/cirugía , Resultado del Tratamiento , Adulto Joven
19.
Front Surg ; 9: 859426, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36034350

RESUMEN

Purpose: This clinical research aims to assess the safety and efficacy of a combination of fusiform capsulectomy of the posterior capsule and percutaneous flexion tendon release in the treatment of a fused knee with severe flexion contracture during total knee arthroplasty (TKA). Methods: A retrospective analysis was performed in three patients (six knees) who had preoperative severe bony fused flexion contracture (>80°) prior to TKA and received a combination of fusiform capsulectomy of posterior capsule and percutaneous flexion tendon release during TKA between January 2016 and December 2019. The range of motion (ROM), knee functional score, postoperative complications, and radiographic results were evaluated. Result: Three patients (six knees) were enrolled in this study. The mean duration of follow-up was 42.83 ± 15.77 months. The postoperative knee ROM was 100.0 (76.0, 102.75) (p < 0.01). The knee society score (KSS) clinical score increased from a preoperative 30.0 (25.0, 36.0) to a postoperative 64.0 (65.0, 78.0) (p < 0.01), and the KSS function score increased from a preoperative 0.0 (0.0, 30.0) to a postoperative 55.0 (40.0, 55.0) (p < 0.01). No implant loosening, infection, neurovascular complications, or revision were recorded in the cohort until the last follow-up. Conclusion: The technique of a combination of fusiform capsulectomy of the posterior capsule and percutaneous flexion tendon release is an effective and safe method during primary TKA for a fused knee with severe flexion contracture.

20.
Eur J Med Res ; 27(1): 79, 2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35642042

RESUMEN

BACKGROUND: Acute lung injury (ALI) caused by intestinal ischemia-reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia-reperfusion conditions. METHODS: To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). RESULTS: C-176 administration significantly attenuated intestinal ischemia-reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNß mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. CONCLUSION: C-176, a selective STING inhibitor, improves intestinal ischemia-reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Lesión Pulmonar Aguda , Daño por Reperfusión , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/terapia , Animales , Caspasa 3 , Masculino , Ratones , Ratones Endogámicos C57BL
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