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OPINION STATEMENT: In addressing Gestational Trophoblastic Neoplasia (GTN), it is imperative to acknowledge the evolving landscape of treatment options, especially in light of the challenges posed by traditional methods. While historically, surgical interventions, radiation therapy, and chemotherapeutic agents have been the mainstays, the emergence of resistance and high-risk scenarios necessitates a reevaluation of our therapeutic approaches. Our review highlights the promising advancements in immunotherapy and molecular targeted therapy as viable alternatives for GTN management. The introduction of immune checkpoint inhibitors and kinase inhibitors offers a paradigm shift, particularly for patients resistant to conventional chemotherapy regimens. These novel therapies not only exhibit efficacy but also demonstrate manageable toxicity profiles, particularly in high-risk cases. However, integrating these innovative treatments into established international guidelines presents a formidable task. As we move forward, it is imperative that future research not only prioritizes fertility preservation but also rigorously evaluates long-term toxicity implications. International collaboration becomes pivotal in addressing the nuances of this rare and complex disease. In conclusion, our review underscores the need for a nuanced approach to GTN treatment, one that prioritizes reduced toxicity and improved quality of life. By embracing the advancements in immunotherapy and molecular targeted therapy, we can pave the way for more effective and patient-centered care in the management of GTN.
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Gerenciamento Clínico , Doença Trofoblástica Gestacional , Imunoterapia , Terapia de Alvo Molecular , Humanos , Feminino , Doença Trofoblástica Gestacional/terapia , Doença Trofoblástica Gestacional/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Gravidez , Imunoterapia/métodos , Terapia Combinada/métodos , Terapia Combinada/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The objective of the study was to find the most effective retracting method for the six maxillary anterior teeth with double-slot lingual brackets using a lever arm and miniscrew system. METHODS: Six finite element models were constructed: (A) a ribbon-wise archwire with a lever arm; (B) a ribbon-wise archwire with a lever arm and a sectional edgewise archwire; (C) a ribbon-wise archwire and a sectional edgewise archwire with a lever arm; (D) an edgewise archwire with a lever arm; (E) an edgewise archwire with a lever arm and a sectional ribbon-wise archwire; and (F) an edgewise archwire and a sectional ribbon-wise archwire with a lever arm. Initial displacements of maxillary teeth driven by a 1.5 N retraction force to the lever arm were analysed. RESULTS: In models B, C, E and F, anterior torque loss and inter-canine distance increases were significantly lower than that of the models without auxiliary archwires. In models C and F, the main archwire was less likely deformed. In models A, B and C, the displacement of canines in sagittal and vertical directions were less than in models D, E and F. CONCLUSIONS: The combination of edgewise and ribbon-wise archwires in double-slot lingual brackets effectively preserves the anterior arch shape. An edgewise archwire with lever arms on the auxiliary sectional ribbon-wise archwire is recommended for better performance in anterior teeth retraction.
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Braquetes Ortodônticos , Análise de Elementos Finitos , Incisivo , Desenho de Aparelho Ortodôntico , Fios Ortodônticos , Técnicas de Movimentação Dentária/métodosRESUMO
Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial-mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.
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Endometriose , Neoplasias Ovarianas , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/patologia , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
AIM: Cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T-cells, plays a key role in tumorigenesis and progression. In the present study, we investigated the effects of three polymorphisms in the CTLA-4 gene on the risk of epithelial ovarian cancer and the clinical outcomes of patients. METHODS: A case-control study was performed in 527 epithelial ovarian cancer patients and 532 controls. Genotypes of three polymorphisms were determined by polymerase chain reaction/ligase detection reaction. A survival analysis was performed in 346 patients who were followed up for more than 3 years and 208 patients who were followed up for more than 5 years. RESULTS: There were significant differences in the genotype and allele distribution frequencies of the rs5742909 C/T polymorphism in CTLA-4 between patients and controls (p = 0.009 and p = 0.04, respectively). Compared with the CC genotype, the CT + TT genotype may significantly decrease the risk of developing epithelial ovarian cancer (OR = 0.69, 95% CI = 0.52-0.91). However, no significant association between the rs231775 G/A and rs3087243 G/A polymorphisms and epithelial ovarian cancer risk was observed. The survival analysis showed that three polymorphisms may not be related to the clinical outcomes of patients. CONCLUSION: Our results suggested that the rs5742909 C/T polymorphism of CTLA-4 may decrease the genetic susceptibility to epithelial ovarian cancer among northern Chinese women.
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Antígeno CTLA-4 , Carcinoma Epitelial do Ovário , Predisposição Genética para Doença , Neoplasias Ovarianas , Antígeno CTLA-4/genética , Carcinoma Epitelial do Ovário/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes with copy number alterations (deletion and duplication region), functional annotation was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region and duplication region. In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YSTs). Moreover, POU5F1 was the most significant mutated gene with mutation frequency >10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region and duplication region) was found in two YST and nuclear staining in two dysgerminomas tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I (DExD/H-box helicase 58)-like receptor, Toll-like receptor and nuclear factor (NF)-kappa. Keratin 4 (KRT4), ribosomal protein L14 (RPL14), proprotein convertase subtilisin/kexin type 6 (PCSK6), poly(A)-binding protein cytoplasmic 3 (PABPC3), and sterile alpha and TIR motif containing 1 (SARM1) mutations were detected in both peripheral blood and tumor samples. Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.
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Mutação , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Ovarianas/genética , Adulto , Variações do Número de Cópias de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Sequenciamento do Exoma , Adulto JovemRESUMO
The first enantioselective total synthesis of cerorubenic acid-III is described in detail. Different strategies and attempts, based on a type II [5+2] cycloaddition reaction, leading to the bicyclo[4.4.1] ring system with a strained bridgehead double bond, are depicted. Furthermore, sodium naphthalenide was found to be efficient in the chemoselective reduction of 8-oxabicyclo[3.2.1]octene, with three transformations completed in one operation. An unusual SN1 transannular cyclization reaction was applied to construct the synthetically challenging vinylcyclopropane moiety. This strategy enabled the total synthesis of cerorubenic acid-III in 19 steps.
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Reação de Cicloadição , Ciclização , EstereoisomerismoRESUMO
OBJECTIVES: The objective of this study was to investigate the optimal range of rotational moment for the mandibular lateral incisor, canine and first premolar to determine tooth movements during orthodontic treatment using hydrostatic stress and logarithmic strain on the periodontal ligament (PDL) as indicators by numerical simulations. MATERIAL AND METHODS: Teeth, PDL and alveolar bone numerical models were constructed as analytical objects based on computed tomography (CT) images. Teeth were assumed to be rigid bodies, and rotational moments ranging from 1.0 to 4.0 Nmm were exerted on the crowns. PDL was defined as a hyperelastic-viscoelastic material with a uniform thickness of 0.25 mm. The alveolar bone model was constructed using a non-uniform material with varied mechanical properties determined based on Hounsfield unit (HU) values calculated using CT images, and its bottom was fixed completely. The optimal range values of PDL compressive and tensile stress were set as 0.47-12.8 and 18.8-51.2 kPa, respectively, whereas that of PDL logarithmic strain was set as 0.15-0.3%. RESULTS: The rotational tendency of PDL was around the long axis of teeth when loaded. The optimal range values of rotational moment for the mandibular lateral incisor, canine and first premolar were 2.2-2.3, 3.0-3.1 and 2.8-2.9 Nmm, respectively, referring to the biomechanical responses of loaded PDL. Primarily, the optimal range of rotational moment was quadratically dependent on the area of PDL internal surface (i.e. area of PDL internal surface was used to indicate PDL size), as described by the fitting formula. CONCLUSIONS: Biomechanical responses of PDL can be used to estimate the optimal range of rotational moment for teeth. These rotational moments were not consistent for all teeth, as demonstrated by numerical simulations. CLINICAL RELEVANCE: The quantitative relationship between the area of PDL internal surface and the optimal orthodontic moment can help orthodontists to determine a more reasonable moment and further optimise clinical treatment.
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Incisivo , Ligamento Periodontal , Dente Pré-Molar , Fenômenos Biomecânicos , Simulação por Computador , Análise de Elementos Finitos , Modelos Biológicos , Ligamento Periodontal/diagnóstico por imagem , Estresse Mecânico , Técnicas de Movimentação DentáriaRESUMO
In the study of oral orthodontics, the dental tissue models play an important role in finite element analysis results. Currently, the commonly used alveolar bone models mainly have two kinds: the uniform and the non-uniform models. The material of the uniform model was defined with the whole alveolar bone, and each mesh element has a uniform mechanical property. While the material of the elements in non-uniform model was differently determined by the Hounsfield unit (HU) value of computed tomography (CT) images where the element was located. To investigate the effects of different alveolar bone models on the biomechanical responses of periodontal ligament (PDL), a clinical patient was chosen as the research object, his mandibular canine, PDL and two kinds of alveolar bone models were constructed, and intrusive force of 1 N and moment of 2 Nmm were exerted on the canine along its root direction, respectively, which were used to analyze the hydrostatic stress and the maximal logarithmic principal strain of PDL under different loads. Research results indicated that the mechanical responses of PDL had been affected by alveolar bone models, no matter the canine translation or rotation. Compared to the uniform model, if the alveolar bone was defined as the non-uniform model, the maximal stress and strain of PDL were decreased by 13.13% and 35.57%, respectively, when the canine translation along its root direction; while the maximal stress and strain of PDL were decreased by 19.55% and 35.64%, respectively, when the canine rotation along its root direction. The uniform alveolar bone model will induce orthodontists to choose a smaller orthodontic force. The non-uniform alveolar bone model can better reflect the differences of bone characteristics in the real alveolar bone, and more conducive to obtain accurate analysis results.
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Ligamento Periodontal , Técnicas de Movimentação Dentária , Fenômenos Biomecânicos , Simulação por Computador , Análise de Elementos Finitos , Humanos , Modelos Biológicos , Estresse MecânicoRESUMO
OBJECTIVE: Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes. METHODS: A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database. RESULTS: The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P < 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively). CONCLUSIONS: TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.
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Carcinoma Epitelial do Ovário/genética , Procedimentos Cirúrgicos de Citorredução , Receptor Celular 2 do Vírus da Hepatite A/genética , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Casos e Controles , China/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ovário/cirurgia , Polimorfismo de Nucleotídeo Único , Prognóstico , Intervalo Livre de Progressão , Regulação para Cima , Adulto JovemRESUMO
The first asymmetric total synthesis of the highly strained compound cerorubenic acid-III is reported. A type II intramolecular [5 + 2] cycloaddition allowed efficient and diastereoselective construction of the synthetically challenging bicyclo[4.4.1] ring system with a strained bridgehead (anti-Bredt) double bond in the final product. A unique transannular cyclization installed the vinylcyclopropane moiety with retention of the desired stereochemistry.
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The first and asymmetric total synthesis of cyclocitrinol, an unusual C25 steroid, has been accomplished in a linear sequence of 18 steps from commercially available compound 11. The synthetically challenging bicyclo[4.4.1] A/B ring system with a strained bridgehead (anti-Bredt) double bond of cyclocitrinol was constructed efficiently and diastereoselectively via a type II intramolecular [5 + 2] cycloaddition.
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OBJECTIVES: Glass fiber reinforced shape memory polyurethane (GFRSMPU) has great potential to be an alternative kind of material for orthodontic archwires for overcoming the disadvantages of metal wires in terms of esthetic and allergy and deficiency of pure shape memory polyurethane (SMPU) wires in mechanical properties. The objective of this study was to investigate the thermo-mechanical properties and shape recovery functions of GFRSMPU and evaluate the feasibility of using this composite for orthodontic archwires. MATERIAL AND METHODS: GFRSMPU were made from short cut glass fibers and SMPU by mixing extrusion. Scanning electron microscope (SEM) and differential scanning calorimetry (DSC) were performed to investigate the distribution of glass fibers in the mixture and glass transition temperature (Tg). Then the thermo-mechanical properties, including tensile modulus, flexural modulus and stress relaxation effects, were measured. Furthermore, shape recovery functions of GFRSMPU characterized by the shape recovery ratio and force were investigated through shape recovery tests, typodont models and finite element analysis (FEA). RESULTS: SEM images indicated that an excellent dispersity of glass fibers was obtained after double-extrusion. DSC experiments showed Tg was not enormously affected with the existence of glass fibers, but the mechanical properties of GFRSMPU were greatly improved. Shape recovery tests showed reduction of shape recovery ratio of the GFRSMPU material with the addition of glass fibers, but dentition aligning time was reduced by 50% in the simulation performed on identical typodont models with GFRSMPU archwires filled with 30 wt.% glass fibers. The FEA results illustrated that the reacting forces of GFRSMPU archwires with 30 wt.% glass fiber was increased by 96.36% compared with pure SMPU archwires. CONCLUSIONS: The mechanical properties of GFRSMPU can be considerably improved by adding glass fibers, and the shape memory function would be well preserved too. Enhanced SMPU owns a good application prospect in orthodontics for dentation aligning on the preliminary stage, as well as other medical fields.
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Materiais Biocompatíveis , Vidro , Teste de Materiais , Poliuretanos/química , Materiais Dentários/química , Maleabilidade , Estresse Mecânico , Propriedades de SuperfícieRESUMO
PURPOSE: During dental implantation, if the temperature within the bone tissue exceeds a critical value, the thermal necrosis of bone cells may take place, inhibiting osseointegration. In contrast to conventional dental implant surgery, a surgery guided by a surgical template is a safer and more efficient technique; however, the temperature within the implant field is more difficult to control, because the surgical guide blocks irrigation water. The purpose of this study was to investigate the temperature distribution in the drilling site when preparing for dental implant placement with a surgical guide, and to derive suggestions for clinical operation. MATERIALS AND METHODS: Initially, the sources of heat during drilling were investigated, and theoretical equations were listed. Subsequently, a measurement system using thermocouples was constructed, with which the temperature increments at specific points in the simulated bone samples were recorded during guided drilling with different cooling methods. Based on the equations and data assessed, a thermal simulation model with a finite element method (FEM) was created, and the temperature change of the whole surgical field was calculated on the basis of the numerical simulation results. Consequently, the point experiencing the highest temperature within the bone was determined. RESULTS: From the experimental measurements, the highest temperature increment was located at a depth of 6 mm without irrigation and at 8 mm with cooling, rather than at the deepest point of the prepared hole. Because the surgical guide blocks the cooling water from entering the drilling site, the biggest increment of temperature using conventional irrigation with the surgical guide was 1.95 times that recorded when using a surgical guide consisting of cooling channels, and 3.6 times that recorded using a drill with an internal cooling hole. And from numerical analysis, during drilling for implant placement site with conventional irrigation, the highest temperature (45.6°C) was close to the critical point at which bone necrosis occurs. CONCLUSIONS: Based on theoretical analysis, experimentation, and FEM simulation, the temperature distribution of the drilling area in the placement of dental implants under surgical guide was determined. For clinical operation, improved cooling methods, such as using a drill with an internal cooling channel, should be used, and the drill should be regularly withdrawn during drilling.
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Temperatura Corporal , Osso e Ossos , Implantes Dentários , Modelos Anatômicos , Osteotomia , Animais , Análise de Elementos Finitos , Humanos , Impressão Tridimensional , Irrigação Terapêutica , TermografiaRESUMO
The observation of an unexpected oxidative rearrangement coupling reaction led to the development of a novel method for the efficient functionalization of tetrahydro-ß-carbolines (THßCs). The treatment of THßCs with photogenerated singlet oxygen (1 O2 ) afforded unstable dioxetanes, which underwent further transformation to form new bonds in the presence of trifluoroacetic acid. This operationally simple protocol exhibits broad functional-group tolerance and is suitable for the late-stage functionalization of complex druglike molecules.
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Aminas/química , Carbolinas/química , Acoplamento Oxidativo , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Processos Fotoquímicos , Oxigênio Singlete/química , Ácido Trifluoracético/químicaRESUMO
Functional and esthetic results require accurate implant placement. We aimed to develop a predictive method for assessing guide layout and error on implant accuracy. A mathematical model for position error analysis was constructed based on triangular mesh data. This model examines the relationship between the spatial shifts of multiple surfaces and the spatial shifts of specific points. It involves encasing these surfaces in a cuboid bounding box and expressing them in a local coordinate system. The influence of positioning surface error and layout of surgical guide were researched with a simulation test. The result shows that error in the implant site position is directly related to the error in the guide locating surface under the same layout. When the guide locating surface layout varies, as the length, width, and height of the minimum cuboid envelope increase, the maximum deviation in the implant site position decreases.
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Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , Simulação por Computador , Próteses e Implantes , Modelos TeóricosRESUMO
Introduction and importance: With the widespread use of positron emission tomography and computed tomography (PET/CT), a significantly greater proportion of patients with advanced ovarian cancer (OC) are now diagnosed with superior renal-vein lymph node metastases involving retrocrural and mediastinal nodes. To the authors' knowledge, retrocrural lymphadenectomy has not yet been reported in patients with OC. The authors performed retrocrural lymph node resection in a patient with ovarian cancer. Case presentation: A 64-year-old woman with ovarian cancer who had not undergone surgery upon initial diagnosis was admitted to the authors' hospital because tumour markers increased during bevacizumab maintenance therapy. PET/CT imaging revealed adnexal masses and multiple metastases in pelvic, para-aortic, retrocrural, and mediastinal lymph nodes. Reduction surgery was performed, and retrocrural lymph nodes were excised. However, the patient's postoperative course was complicated by a chylothorax. Because of the failure of conservative treatment, interventional embolization was performed, but failed to obstruct lymphatic vessels. The patient underwent reoperation. A fistula was located where Hem-o-lock clips penetrated the pleura, clearly indicating the injury site, which was then sutured and embedded in the surrounding diaphragmatic tissue and filled with gel sponge. The patient recovered from chylous leakage postoperatively. She later underwent chemotherapy and targeted maintenance therapy. Clinical discussion: The authors may have injured the communicating branch of the thoracic duct posterior to the diaphragm during the first operation and did not ligate it. The accumulated chylous fluid finally penetrated through the weak point on the pleura and led to chylothorax 3 days later. If conservative treatment or interventional embolization are unsuccessful, surgical treatment should be selected in time. Conclusion: The location of the retrocrural lymph node at the anastomosis of the chylous cistern and the thoracic duct may pose a significant risk of chylous leakage as a complication of lymphadenectomy. Full exposure of the surgical field and thorough ligation of the lymphatic vessels may lead to successful superior renal-vein lymphadenectomy.
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Accumulating researches have reported that miR-17-92 cluster expression has strong association with tumorigenesis. In this study, we investigated the effects of 2 genetic polymorphisms in the promoter region of the miR-17-92 cluster and the risk and prognosis of endometrial cancer in northern Chinese women. Two polymorphisms (rs9588884 and rs982873) in the promoter of miR-17-92 cluster were genotyped by polymerase chain reaction and ligase detection reaction (PCR-LDR) in398 EC patients and 420 controls. The levels of miR-17-92 mRNA were investigated in 65EC tissues by real-time quantitative polymerase chain reaction (RT-qPCR). The impact of genetic features on the risk and clinical outcomes of EC was analyzed. The prognostic value of hsa-miR-17 and hsa-miR-20a in EC patients was assessed using the Kaplan-Meier plotter database. The results showed that a significant decrease in risk of EC with rs9588884 (GG vs CC: ORâ =â 0.49, 95% CIâ =â 0.32-0.78, Pâ =â .002; G vs C: ORâ =â 0.75, 95% CIâ =â 0.62-0.91, Pâ =â .005, respectively). Similarly, association was found between rs982873 and a decreased risk of EC (CC vs TT: ORâ =â 0.53, 95% CIâ =â 0.34-0.82, Pâ =â .004; C vs T: ORâ =â 0.77, 95% CIâ =â 0.63-0.94, Pâ =â .010, respectively). Moreover, survival analysis showed that the CG or GG genotype of rs9588884 may significantly increase overall survival (OS) compared with the CC genotype in the 5-year follow-up (HRâ =â 0.49, 95% CIâ =â 0.29-0.82 and HRâ =â 0.36, 95% CIâ =â 0.16-0.83, respectively). RT-qPCR results showed that the expression level of miR-17-92 mRNA in EC tissues with the rs9588884 GG genotype was significantly lower than those with the GCâ +â CC genotype (Pâ =â .030). However, there was no significant difference in the prognosis and expression level of miR-17-92mRNA in tissues of EC patients with different genotypes of rs982873 (Pâ =â .343). In addition, analysis using Kaplan-Meier plotter database showed that high hsa-miR-20a expression was significantly correlated with poor OS in EC patients (HRâ =â 1.63, 95% CIâ =â 1.02-2.61, Pâ =â .039). The genetic polymorphisms rs9588884 and rs982873 in the promoter of miR-17-92 cluster decreased EC risk. Both rs9588884 and the expression level of hsa-miR-20a mRNA may be associated with its clinical outcome in EC patients.
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Neoplasias do Endométrio , MicroRNAs , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , RNA Longo não Codificante , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Regiões Promotoras Genéticas/genética , Predisposição Genética para Doença , China/epidemiologia , Povo Asiático/genética , Genótipo , Estudos de Casos e Controles , Idoso , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: As a new intelligent polymer material, shape memory polymer (SMP) was a potential orthodontic appliance material. OBJECTIVE: This study aimed to investigate the thermodynamic responses of SMP under different loads via finite element analysis (FEA). METHODS: FEA specimens with a specification of 0.1 × 0.1 × 1 mm were designed. One end of the specimen was fixed, and the other was subjected to displacement load. Different loading, cooling, and heating rates were separately exerted on the specimen in its shape recovery process and used to observe the responses of the SMP constitutive model. Furthermore, specimens with various tensile elongation and sectional areas were simulated and used to elucidate their effect on shape recovering force. RESULTS: The specimens obtained a similar stress of 0.5, 0.44, and 1.07 Mpa for different loading, cooling, and heating rates after a long time. The shape recovering force of specimen increased from 0.0102 to 0.0315 N when the elongation improved from 10% to 40% and to 0.0408 N when the sectional areas were expanded to 0.2 × 0.2 mm. CONCLUSION: The stiffness of SMP was small at a high temperature but large at a low temperature. The effects of the loading, cooling, and heating rates on SMP can be eliminated after a long time. Furthermore, it was possible to increase the recovering force by increasing the elongation or expanding the sectional area of the specimen. The force was quadratically dependent on the elongation ratio.
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Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.
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Linfócitos T CD8-Positivos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , RNA-Seq/métodos , Biomarcadores Tumorais/genética , Análise de Célula Única/métodos , Regulação Neoplásica da Expressão Gênica , Análise da Expressão Gênica de Célula ÚnicaRESUMO
This study aimed to develop a constitutive model for human periodontal ligament (PDL) by combining the hyperelastic and viscosity models. We performed the finite element analysis (FEA) to simulate the experimental processes of the PDL in vitro and in vivo tests to verify the developed model. The FEA results indicated that the simulative curves were consistent with the experimental curves in the PDL in vitro tests. Moreover, for the in vivo measurements, the simulative result of 0.6258 N was similar to the experimental value of 0.65 N. The study results can help orthodontists better understand the biomechanical characteristics of PDL.