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Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.
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Empalme Alternativo , Exones , Genoma Humano , Elementos Alu , Animales , Secuencia de Bases , Células Madre Embrionarias/metabolismo , Evolución Molecular , Humanos , Intrones , Mamíferos/genética , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Alineación de SecuenciaRESUMEN
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.
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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 , RatasRESUMEN
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.
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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 .
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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 .
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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 .
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Pueblo Asiatico , Pabellón Auricular , Estética , Humanos , Femenino , Pueblo Asiatico/estadística & datos numéricos , Adulto , Pabellón Auricular/anatomía & histología , Pabellón Auricular/cirugía , Adulto Joven , Fotograbar , BellezaRESUMEN
BACKGROUND: Research studies on Asian women's preferences for breast augmentation and the factors that influence decision-making are scarce or unrepresentative. METHODS: This study was conducted from September 2016 to September 2017, a period of one year. We developed a questionnaire for Chinese female with breast augmentation intentions based on the Breast-Q questionnaire, the world's most popular breast augmentation assessment tool, and conducted questionnaire surveys in 35 hospitals located in 19 provinces in mainland China among female who came to hospitals to inquire about breast augmentation surgery. RESULTS: A total of 2066 questionnaires were collected from female interested in breast augmentation. The age range at the time of response was 19-53 years (mean 31.2 ± 6.8 years). More than half of the respondents (58.1%) were married, and 70.4% of them had children. The respondents rated their dressed image significantly higher than their nude image. Their partners also rated their breast image poorly, with 43% rating it fair and 30.4% negatively. Internal reasons, such as improving self-confidence and creating a better body image, were the main motivators for breast augmentation. More than half of the respondents had only limited understanding of breast augmentation surgery or had heard of it but did not fully understand it (33.2% and 27.5%, respectively), and 69.4% had considered breast augmentation for less than three years. A total of 49.2% of the respondents learned about breast augmentation surgery through the Internet. A total of 43.8% of the respondents did not receive support from family members or partners. Surgical safety (20.4%), surgical effect (17.1%), and surgeon's skill (16.6%) were given the highest priority. The surgeon's professionalism, popularity, and academic background were also high on people's list of considerations. CONCLUSIONS: The results of our breast augmentation survey provide data on many Chinese women considering breast augmentation. This will help plastic surgeons better understand the characteristics, preferences, and concerns of Chinese women undergoing breast augmentation and will be used to guide patient-doctor communication and help Chinese women make the most informed decisions. 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 .
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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. .
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Disección , Arterias Temporales , Humanos , Arterias Temporales/diagnóstico por imagen , Inyecciones , CadáverRESUMEN
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 .
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Exosomas , Supervivencia de Injerto , Ratones , Animales , Humanos , Exosomas/trasplante , Ratones Desnudos , Tejido Adiposo/trasplante , Criopreservación , Células Madre , FibrosisRESUMEN
The novel anti-PD-L1/TGFBR2-ECD fusion protein (BR102) comprises an anti-PD-L1 antibody (HS636) which is fused at the C terminus of the heavy chain to a TGF-ß1 receptor â ¡ ectodomain (TGFBR2-ECD), and which can sequester the PD-1/PD-L1 pathway and TGF-ß bioactivity in the immunosuppressive tumor microenvironment. In the expression of TGFBR2-ECD wild-type fused protein (BR102-WT), a 50 kDa clipped species was confirmed to be induced by proteolytic cleavage at a "QKS" site located in the N-terminus of the ectodomain, which resulted in the formation of IgG-like clipping. The matrix metalloproteinase-9 was determined to be associated with BR102-WT digestion. In addition, it was observed that the N-glycosylation modifications of the fusion protein were tightly involved in regulating proteolytic activity and the levels of cleavage could be significantly suppressed by MMP-inhibitors. To avoid proteolytic degradation, eliminating protease-sensitive amino acid motifs and introducing potential glycosylation were performed. Three sensitive motifs were mutated, and the levels of clipping were strongly restrained. The mutant candidates exhibited similar binding affinities to hPD-L1 and hTGF-ß1 as well as highly purified BR102-WT2. Furthermore, the mutants displayed more significant proteolytic resistance than that of BR102-WT2 in the lysate incubation reaction and the plasma stability test. Moreover, the bifunctional candidate Mu3 showed an additive antitumor effect in MC38/hPD-L1 bearing models as compared to that of with anti-PD-L1 antibody alone. In conclusion, in this study, the protease-sensitive features of BR102-WT were well characterized and efficient optimization was performed. The candidate BR102-Mutants exhibited advanced druggability in drug stability and displayed desirable antitumor activity.
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Anticuerpos Antineoplásicos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias del Colon/terapia , Procesamiento Proteico-Postraduccional , Receptor Tipo II de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/genética , Animales , Anticuerpos Antineoplásicos/genética , Anticuerpos Antineoplásicos/inmunología , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Células CHO , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Cricetulus , Femenino , Glicosilación , Humanos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Endogámicos C57BL , Mutación , Dominios Proteicos , Proteolisis , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta/inmunología , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/farmacología , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/inmunología , Microambiente Tumoral/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Osteoarthritis (OA) is a common type of degenerative joint diseases that is regulated by a combination of complex intercellular signals and modulators, including non-coding RNAs. Mounting evidence suggests that miR-31-5p is physiologically involved in the regulation of chondrocytes, but the mechanism remains unclear. METHODS: Expression levels of miR-31-5p and SOX4 in OA cartilage tissues and in IL-1ß-stimulated chondrocytes were examined by quantification polymerase chain reaction (q-PCR) or immunohistochemistry assays. Cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Expression of LC3 was detected using immunofluorescence staining. Expressions of autophagy-related proteins and extracellular regulated protein kinase (ERK)/mechanical target of rapamycin kinase (mTORC1) signal-related proteins were measured by Western blot analysis. Molecular interaction was validated by dual luciferase reporter assay. RESULTS: Downregulation of miR-31-5p and upregulation of SOX4 were observed in both OA patients and OA chondrocytes. Mechanistic experiments revealed that miR-31-5p negatively modulated SOX4 expression by directly targeting its 3'- untranslated region. Moreover, overexpression of miR-31-5p suppressed the activation of mTORC1 in an ERK-dependent manner by inhibiting SOX4. Further functional experiments demonstrated that overexpressing miR-31-5p in OA chondrocytes markedly promoted its proliferation and autophagy while inhibiting apoptosis. However, these effects were abolished by overexpression of SOX4 or treatment with 3BDO, an mTOR activator. CONCLUSION: These results demonstrated that miR-31-5p enhanced survival and autophagy of OA chondrocytes through inactivation of mTORC1 via directly targeting SOX4, suggesting that miR-31-5p may play a protective role in OA progression.
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MicroARNs , Osteoartritis , Apoptosis/fisiología , Autofagia/genética , Condrocitos/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Proteínas Quinasas/metabolismo , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Sirolimus/metabolismoRESUMEN
N6-methyladenosine (m6A) is the most abundant posttranscriptional methylation modification that occurs in mRNA and modulates the fine-tuning of various biological processes in mammalian development and human diseases. In this study we investigated the role of m6A modification in the osteogenesis of mesenchymal stem cells (MSCs), and the possible mechanisms by which m6A modification regulated the processes of osteoporosis and bone necrosis. We performed systematic analysis of the differential gene signatures in patients with osteoporosis and bone necrosis and conducted m6A-RNA immunoprecipitation (m6A-RIP) sequencing to identify the potential regulatory genes involved in osteogenesis. We showed that fat mass and obesity (FTO), a primary m6A demethylase, was significantly downregulated in patients with osteoporosis and osteonecrosis. During the differentiation of human MSCs into osteoblasts, FTO was markedly upregulated. Both depletion of FTO and application of the FTO inhibitor FB23 or FB23-2 impaired osteogenic differentiation of human MSCs. Knockout of FTO in mice resulted in decreased bone mineral density and impaired bone formation. PPARG, a biomarker for osteoporosis, was identified as a critical downstream target of FTO. We further revealed that FTO mediated m6A demethylation in the 3'UTR of PPARG mRNA, and reduced PPARG mRNA stability in an YTHDF1-dependent manner. Overexpression of PPARG alleviated FTO-mediated osteogenic differentiation of MSCs, whereas knockdown of PPARG promoted FTO-induced expression of the osteoblast biomarkers ALPL and OPN during osteogenic differentiation. Taken together, this study demonstrates the functional significance of the FTO-PPARG axis in promoting the osteogenesis of human MSCs and sheds light on the role of m6A modification in mediating osteoporosis and osteonecrosis.
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Células Madre Mesenquimatosas , Osteonecrosis , Osteoporosis , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Animales , Diferenciación Celular , Humanos , Mamíferos/genética , Mamíferos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Noqueados , Osteogénesis , Osteonecrosis/metabolismo , Osteoporosis/genética , PPAR gamma/metabolismo , ARN Mensajero/metabolismoRESUMEN
We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.
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COVID-19/sangre , Quimiocina CXCL10/sangre , Interleucina-7/sangre , SARS-CoV-2/metabolismo , Índice de Severidad de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Breast ptosis is a deformity commonly found in patients seeking breast augmentation. Current mastopexy techniques rely on incisions on the breast to correct ptosis; nonetheless, they leave extensive scars. Having to opt for a visibly scarred breast over a ptotic breast can be a difficult choice. OBJECTIVES: We sought an innovative internal suture mastopexy for hypomastia of mild breast ptosis. METHODS: A procedure that left a tiny scar on the nipple-areolar complex was introduced. This method was safe and efficient when combining mastopexy with augmentation. RESULTS: Overall, 53 patients underwent this operation in the Plastic and Cosmetic Department of Guangdong Second Provincial General Hospital from January 1, 2013, to June 30, 2017, with a mean follow-up of 38 ± 16 months. The pre-operation and post-operation SN-N lines (the distance from the sternal notch to the nipple) were 21.8 ± 1.2 cm and 20.7 ± 1.0 cm, respectively; the difference was statistically significant (P<0.05). The patients and surgeon expressed satisfaction with the procedure. CONCLUSION: Based on the results of the present study, which included more than 50 patients, we believe that internal suture mastopexy can be used as an effective alternative hypomastia in patients with mild breast ptosis. LEVEL OF EVIDENCE IV: 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. .
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Mamoplastia , Estudios de Cohortes , Estética , Humanos , Pezones/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Results regarding immediate prosthetic breast reconstruction after postmastectomy radiation therapy (PMRT) have been inconsistent. OBJECTIVES: The authors aimed to assess the efficacy and safety of PMRT before immediate prosthetic breast reconstruction for patients with breast cancer. METHODS: Electronic databases (PubMed, EmBase, and the Cochrane Library) were systematically searched to identify eligible studies from their inception until March 2020. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was applied as an effect estimate and calculated using the random-effects model. RESULTS: Nineteen studies including a total of 6757 patients were selected for final meta-analysis. The pooled OR showed that PMRT was associated with a higher incidence of reconstruction failure (OR = 2.57; 95% CI =1.55-4.26; Pâ <â 0.001), capsular contracture (OR = 5.99; 95% CI = 3.12-11.47; Pâ <â 0.001), and overall complications (OR = 2.52; 95% CI = 1.68-3.79; Pâ <â 0.001). It was also associated with a lower incidence of patient satisfaction (OR = 0.29; 95% CI = 0.16-0.52; Pâ <â 0.001) and good aesthetic results (OR = 0.25; 95% CI = 0.12-0.52; Pâ <â 0.001) compared with those who did not undergo PMRT. These significant associations could be affected by study design, mean age, stage of immediate breast reconstruction, follow-up, and study quality. CONCLUSIONS: Although PMRT is the standard adjuvant therapy for mastectomy patients treated with immediate implant-based breast reconstruction, PMRT for patients undergoing immediate implant-based breast reconstruction has been associated with high risks of reconstruction failure, capsular contracture, and overall complications as well as low incidences of patient satisfaction and good aesthetic results.
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Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/efectos adversos , Mastectomía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Radioterapia Adyuvante/efectos adversosRESUMEN
As the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. However, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. Therefore, in this work, we developed a NRGK (nonparametric regression with Gaussian kernel) method, which aimed to identify the critical components that affect product titres during the development of cell culture media. With this nonparametric model, we successfully identified the important components that were neglected by the conventional PLS (partial least squares regression) method. The superiority of the NRGK method was further verified by ANOVA (analysis of variance). Additionally, it was proven that the selection accuracy was increased with the NRGK method because of its ability to model both the nonlinear and linear relationships between the medium components and titres. The application of this NRGK method provides new perspectives for the more precise identification of the critical components that further enable the optimization of media in a shorter timeframe.
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Algoritmos , Animales , Células CHO , Cricetulus , Medios de Cultivo , Análisis de los Mínimos Cuadrados , Proyectos de InvestigaciónRESUMEN
Triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis due to the lack of an effective targeted therapy. Histone lysine methyltransferases (KMTs) have emerged as attractive drug targets for cancer therapy. However, the function of the majority of KMTs in TNBC has remained largely unknown. In the current study, we found that KMT nuclear receptor binding SET domain protein 2 (NSD2) is overexpressed in TNBC tumors and that its overexpression is associated with poor survival of TNBC patients. NSD2 regulates TNBC cell survival and invasion and is required for tumorigenesis and tumor growth. Mechanistically, NSD2 directly controls the expression of EGFR and ADAM9, a member of the ADAM (a disintegrin and metalloproteinase) family that mediates the release of growth factors, such as HB-EGF. Through its methylase activity, NSD2 overexpression stimulates EGFR-AKT signaling and promotes TNBC cell resistance to the EGFR inhibitor gefitinib. Together, our results identify NSD2 as a major epigenetic regulator in TNBC and provide a rationale for targeting NSD2 alone or in combination with EGFR inhibitors as a targeted therapy for TNBC.
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Proteínas ADAM/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/fisiología , Neoplasias de la Mama Triple Negativas/fisiopatología , Proteínas ADAM/genética , Animales , Línea Celular Tumoral , Proliferación Celular/fisiología , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Técnicas de Silenciamiento del Gen , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/fisiopatología , Proteínas Represoras/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: The addition of the stromal vascular fraction (SVF) can enhance the postoperative survival rate of fat. However, a universal SVF application method is currently unavailable. Therefore, a simple and convenient guideline for SVF addition is needed for its clinical application. OBJECTIVES: The authors sought to evaluate whether SVF can improve fat survival after large-volume fat grafting and to find a simple and convenient standard for the clinical use of SVF. METHODS: Patient fat samples were obtained after liposuction for SVF preparation and grafting. Four types of grafts were prepared with different SVF ratios: 0:1, 1:1, 2:1, and 4:1 SVF:fat. After intensive mixing, fat grafts (5 mL) were randomly injected into both sides of the backs of athymic rats (n = 15). At 24 hours and 1, 3, 6, and 9 months after the operation, microcomputed tomography scanning was performed to calculate the fat survival rate. RESULTS: Nine months after the operation, the survival rates of fat in the 4 groups were 8.89 ± 1.62% (0:1), 18.26 ± 3.85% (1:1), 8.83 ± 1.46% (2:1), and 7.96 ± 1.31% (4:1). The 1:1 group exhibited the greatest survival rate (P < 0.01), and the adipose tissue histological patterns and blood vessel quality were enhanced compared with those in the other groups. CONCLUSIONS: An appropriate SVF ratio can increase the fat survival rate after large-volume fat grafting, but no linear relationship exists between the SVF ratio and fat survival. The optimal SVF:fat ratio for grafting is 1:1.
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Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/trasplante , Células del Estroma/trasplante , Microtomografía por Rayos X , Adulto , Animales , Células Cultivadas , Femenino , Supervivencia de Injerto , Xenoinjertos , Humanos , Lipectomía , Células Madre Mesenquimatosas/patología , Modelos Animales , Ratas Desnudas , Adulto JovenRESUMEN
BACKGROUND: Filler injection is a popular cosmetic procedure, but it can entail vascular complications. Periorbital injections have the highest risk within the entire injection area. OBJECTIVES: The authors sought to systematically screen for periorbital arterial variations prior to treatment. METHODS: The external carotid arteries of 10 cadaveric heads were infused with adequate lead oxide contrast. The facial and superficial temporal arteries of another 11 cadaveric heads were injected with the contrast in sequential order. Computed tomography (CT) scanning was performed after injection of contrast, and 3-dimensional (3D) CT scans were reconstructed using validated algorithms. RESULTS: Three types of periorbital blood vessels were found to derive from the ophthalmic artery, including 30% directly originating from the ophthalmic artery, 65% originating from its trochlear branch, and 5% originating from its supraorbital branch. In the forehead, the ophthalmic artery, originating from the internal carotid arteries, formed anastomoses between the frontal branch of the superficial temporal artery, originating from the external carotid artery, with the deep and superficial branches of the supratrochlear and supraorbital arteries, respectively. The lateral orbit and malar plexus can be classified into 4 types based on the trunk artery: the zygomatic orbital artery (27%), the transverse facial artery (23%), the premasseteric branch of the facial artery (19%), and all 3 contributing equally (31%). CONCLUSIONS: Postmortem 3D CT can map periorbital arterial variations. The branching pattern of the ophthalmic artery, the ophthalmic angiosome in the forehead, and the distribution of the lateral orbit and malar plexus were identified at high resolution to guide clinical practice.
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Variación Anatómica , Técnicas Cosméticas/efectos adversos , Rellenos Dérmicos/administración & dosificación , Embolia/prevención & control , Arteria Oftálmica/anatomía & histología , Adulto , Cadáver , Embolia/etiología , Femenino , Frente/irrigación sanguínea , Frente/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Arteria Oftálmica/diagnóstico por imagen , Órbita/irrigación sanguínea , Órbita/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: The carrier of hydroxyethyl starch (HES) may play a critical role in kidney injury in fluid resuscitation. This study aimed mainly to compare effects of pyruvate-enriched saline with normal saline (NS) and acetate Ringer's (AR) solution as a carrier in HES130/0.4 on kidney function in rats subjected to severe burns. METHODS: Using a lethal burn model, 140 rats were randomly allocated in seven groups (n = 20): sham group (group S); no fluid after burn (group N); burn resuscitated with NS (group NS); burn resuscitated with pyruvate saline (group PS); burn resuscitated with AR plus pyruvate-HES (group SP); burn resuscitated with AR plus acetate-HES (group SA), and burn resuscitated with AR plus NS-HES (group SN). A low volume (18.75 mL·kg-1 during 12 h) of HES130/0.4 was infused with the ratio of 1:1 to crystalloids. Renal surface blood flow, blood creatinine and blood urea nitrogen, early sensitive indicators of kidney function: alpha-1 microglobulin, cystatin-C, and neutrophil gelatinase-associated lipocalin in blood and urine, and kidney tissue water contents were determined. Renal histopathological alterations with Paller scores were also measured at 8 h and 24 h after burn (n = 10), respectively. RESULTS: The results showed in a comparable manner that group SP was the best in three HES groups and group PS was superior to group NS in renal preservation; group SP appeared significantly beneficial compared with group PS in renal surface blood flow, cystatin-C, neutrophil gelatinase-associated lipocalin, water contents, and Paller scores at 8-h or both time points after burn, respectively (all P < 0.05). CONCLUSIONS: The carrier of HES130/0.4 played a crucial role in kidney injury in fluid resuscitation of rats subjected to severe burns. Pyruvate-enriched HES130/0.4 was superior and HES130/0.4, per se, might be not renocytotoxic, but renoprotective. Further studies are warranted.