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Highly sensitive and specific biomarker detection is of outstanding importance for the diagnosis and treatment of cancers. Herein, we developed robust photoelectrochemical (PEC) biosensors with low background noise and high sensitivity based on a heterojunction, which can improve semiconductor photoelectric properties by limiting the recombination of photogenerated electron-hole pairs and successfully widening the range of light absorption. Alpha-fetoprotein (AFP) was used as a target model to examine the analytical performances of the designed PEC biosensors. ZnO/Cs3MnBr5 heterogeneous film with a uniform porous structure and large surface area enhanced electron transfer and biomolecule immobilization, and significantly increased the photocurrent response. Under the optimal conditions, the designed PEC biosensor exhibited a linear detection range of 0.01-500 ng/mL and a detection limit of 12 pg/mL. In addition, this PEC biosensor performed well when testing human serum samples and exhibited good repeatability, stability over time, and specificity, showing enormous potential for the detection of cancer markers in future biological and clinical research.
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OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46ï¼P =0.50; χ2=0.03ï¼P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04ï¼P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00ï¼P =0.09; t =0.94ï¼P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53ï¼P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.
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Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Transplante Autólogo , Humanos , Estudos Retrospectivos , Infecções Bacterianas/prevenção & controle , Antibacterianos , MasculinoRESUMO
Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.
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BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Hepatectomia , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
PURPOSE: This work proposes a robot-assisted augmented reality (AR) surgical navigation system for mandibular reconstruction. The system accurately superimposes the preoperative osteotomy plan of the mandible and fibula into a real scene. It assists the doctor in osteotomy quickly and safely under the guidance of the robotic arm. METHODS: The proposed system mainly consists of two modules: the AR guidance module of the mandible and fibula and the robot navigation module. In the AR guidance module, we propose an AR calibration method based on the spatial registration of the image tracking marker to superimpose the virtual models of the mandible and fibula into the real scene. In the robot navigation module, the posture of the robotic arm is first calibrated under the tracking of the optical tracking system. The robotic arm can then be positioned at the planned osteotomy after the registration of the computed tomography image and the patient position. The combined guidance of AR and robotic arm can enhance the safety and precision of the surgery. RESULTS: The effectiveness of the proposed system was quantitatively assessed on cadavers. In the AR guidance module, osteotomies of the mandible and fibula achieved mean errors of 1.61 ± 0.62 and 1.08 ± 0.28 mm, respectively. The mean reconstruction error of the mandible was 1.36 ± 0.22 mm. In the AR-robot guidance module, the mean osteotomy errors of the mandible and fibula were 1.47 ± 0.46 and 0.98 ± 0.24 mm, respectively. The mean reconstruction error of the mandible was 1.20 ± 0.36 mm. CONCLUSIONS: The cadaveric experiments of 12 fibulas and six mandibles demonstrate the proposed system's effectiveness and potential clinical value in reconstructing the mandibular defect with a free fibular flap.
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Realidade Aumentada , Retalhos de Tecido Biológico , Reconstrução Mandibular , Robótica , Cirurgia Assistida por Computador , Humanos , Reconstrução Mandibular/métodos , Cirurgia Assistida por Computador/métodos , Retalhos de Tecido Biológico/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgiaRESUMO
Neuroendocrine neoplasms (NENs) are rare heterogeneous tumors that can develop in almost any organ, with the digestive organs, including the gastrointestinal tract and pancreas being the most commonly affected sites. Despite the fact that advances in initial therapies have progressed, there is presently no recognized effective treatment for advanced NEN. Immune checkpoint inhibitors (ICIs) have shown superior efficacy in treating several types of solid tumors. Despite their successful role in the treatment of partial NENs, such as small cell lung cancer, and Merkel cell carcinoma, the role of ICIs in most of the NENs remains limited. Nevertheless, due to their specific anti-tumor mechanisms and acceptable safety profile, ICIs are a promising avenue for further study in NENs therapy. Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy, and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies. Therefore, the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system, with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor. Furthermore, this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.
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Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/tratamento farmacológico , Resultado do Tratamento , Imunoterapia/efeitos adversos , Terapia Combinada , Pâncreas/patologiaRESUMO
BACKGROUND: This study aimed to accurately evaluate the matching of proximal and distal femoral segments and fitting of the femur-femoral stem in patients with Crowe type IV developmental dysplasia of the hip (DDH) who have undergone subtrochanteric osteotomy at different locations with an implanted Wagner cone stem to improve the rate of the bone union at the osteotomy site. METHODS: Three-dimensional femur morphology of 40 patients with Crowe type IV DDH was evaluated at each cross-section to determine the femoral cortical bone area. This study focused on five osteotomy lengths (2.5, 3, 3.5, 4, and 4.5 cm). The overlapped area between the proximal and distal cortical bone segments was defined as the contact area (S, mm2), and the contact area to distal cortical bone area ratio was defined as the coincidence rate (R). Three indicators were used to evaluate the matching and fitting of the osteotomy sites with the implanted Wagner cone stems: (1) higher S and R between the proximal and distal segments; (2) the effective fixation length of the femoral stem at the distal segments being at least 1.5 cm; and (3) osteotomy did not involve the isthmus. RESULTS: In all groups, S significantly decreased in the two proximal levels above the 0.5 cm level below the lesser trochanter (LT) compared with those below this level. In comparison, at osteotomy lengths from 2.5 to 4 cm, R significantly decreased in the three proximal levels. The optimal osteotomy levels ranged from 1.5 and 2.5 cm below the LT for an appropriately sized stem. CONCLUSIONS: Subtrochanteric osteotomy at the optimal level not only ensures fitting of the femur-femoral stem but also meets the requirements of a higher S and R to ensure adequate reduction and stabilization at the osteotomy site, which may contribute to the bone union. Although the optimal osteotomy level varies with the size of the femoral stem and the length of the subtrochanteric osteotomy, the optimal osteotomy levels for an appropriately sized Wagner cone femoral stem implantation range from 1.5 to 2.5 cm below the LT.
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Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Sinostose , Humanos , Artroplastia de Quadril/métodos , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/cirurgia , Displasia do Desenvolvimento do Quadril/cirurgia , Estudos Retrospectivos , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Osteotomia/métodos , Sinostose/cirurgiaRESUMO
OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage â ¢, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 µmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (Pï¼0.001), ECOG ≥2 (P=0.011) and ISS stage â ¢ ï¼P=0.024ï¼ were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779ï¼95%CI: 0.682-0.875ï¼. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION: Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage â ¢ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.
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Infecção Hospitalar , Mieloma Múltiplo , Humanos , Nomogramas , Mieloma Múltiplo/metabolismo , Prognóstico , Estudos Retrospectivos , Proteína C-ReativaRESUMO
Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.
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Arsenic (As) is a toxic pollutant in the atmosphere. The atmospheric As concentration is high over the East Asian continent. At present, there is less research on the long-term trend of atmospheric arsenic pollution, which is not conducive to understanding its behavior. Total suspended particulate matter (TSP) samples were collected in Qingdao in autumn and winter from 2016 to 2020 to analyze total arsenic (TAs), As(V) and As(III). The interannual variation patterns, influencing factors and health risks of arsenic concentrations in aerosols were discussed. The results showed that As(V) is the dominant species of arsenic in aerosols. The average concentration of TAs gradually decreased and the proportion of As(III) increased during autumn and winter from 2016 to 2020. The levels of TAs, As(V) and As(III) in aerosols increased during the heating period and on polluted days. Negative correlation between TAs/TSP and TSP indicated that higher concentrations of TSP in the atmosphere would reduce the content of TAs in particulate matter. The increase of secondary aerosol particles played a dilution effect. Mobile source emissions, biomass and coal combustion were main sources of atmospheric arsenic. The distribution range of large potential sources of atmospheric arsenic decreased from 2016 to 2020, and concentrated, mainly in parts of Shandong province and its offshore areas. Local sources contributed the most to atmospheric arsenic pollution in Qingdao in autumn and winter. TAs, As(V) and As(III) posed a low non-carcinogenic risk and a negligible carcinogenic risk to adults and children. This study reveals the influence of strict air pollution control policies on the speciation and source of arsenic in aerosols.
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Poluentes Atmosféricos , Arsênio , Criança , Humanos , Poluentes Atmosféricos/análise , Arsênio/análise , Material Particulado/análise , Estações do Ano , China , Aerossóis/análise , Monitoramento AmbientalRESUMO
BACKGROUND: Augmented reality (AR) navigation has been developed in recent years and can overcome some limitations of existing technologies. This study aimed to investigate a novel method of fibula free flap (FFF) osteotomy based on AR technology through a cadaver study. METHODS: One mandible, seven fibulas, and seven lower limb specimens underwent computed tomography (CT) examination. We used the professional software Proplan CMF 3.0 to design a defective mandible model and created fourteen virtual reconstruction plans using the fibulas and lower limb specimens. The AR-based intraoperative guidance software prototype was developed using the Unity Real-Time Development Platform, and virtual plans were transferred into this software prototype. We used AR-based surgical navigation to guide the FFF osteotomy and used these fibular segments to reconstruct the defective mandible model. After reconstruction, all segments were scanned by CT. Osteotomy accuracy was evaluated by measuring the length and angular deviation between the virtual plan and the final result. The reconstruction precision was reflected by the volume overlap rate and average surface distance between the planned and obtained reconstruction. RESULTS: The length difference, angular deviation, volume overlap rate and average surface distance of the in vitro group were 1.03±0.68 mm, 5.04±2.61°, 95.35±1.81%, and 1.02±0.27 mm, respectively. Those of the in vivo group were 1.18±0.84 mm, 5.45±1.47°, 95.31±2.09%, and 1.22±0.12 mm. CONCLUSIONS: Due to the ideal result of cadaver experiments, an AR-based FFF osteotomy guided system may become a novel approach to assist FFF osteotomy for the reconstruction of defective mandibles.
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Realidade Aumentada , Retalhos de Tecido Biológico , Reconstrução Mandibular , Cirurgia Assistida por Computador , Humanos , Reconstrução Mandibular/métodos , Mandíbula/cirurgia , Retalhos de Tecido Biológico/cirurgia , Cirurgia Assistida por Computador/métodosRESUMO
BACKGROUND: Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM: To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS: PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS: This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION: This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
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The 3D printed porous titanium alloy scaffolds are beneficial to enhance angiogenesis, osteoblast adhesion, and promote osseointegration. However, titanium alloys are biologically inert, which makes the bond between the implant and bone tissue weak and prone to loosening. Inspired by the natural biological marine mussels, we designed four-claw-shaped mussel-derived bioactive peptides for the decoration of porous titanium alloy scaffolds: adhesion peptide-DOPA, anchoring peptide-RGD and osteogenic-inducing peptide-BMP-2. And the bifunctionalization of 3D-printed porous titanium alloy scaffolds was evaluated in vivo in a rabbit model of bone defect with excellent promotion of osseointegration and mechanical stability. Our results show that the in vivo osseointegration ability of the modified 3D printed porous titanium alloy test piece is significantly improved, and the bifunctional polypeptide coating group E has the strongest osseointegration ability. In conclusion, our experimental design partially solves the problems of stress shielding effect and biological inertness, and provides a convenient and feasible method for the clinical application of titanium alloy implants in biomedical implant materials.
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Bivalves , Titânio , Animais , Coelhos , Titânio/química , Porosidade , Projetos de Pesquisa , Impressão Tridimensional , Ligas , OsseointegraçãoRESUMO
BACKGROUND: Marker-based augmented reality (AR) calibration methods for surgical navigation often require a second computed tomography scan of the patient, and their clinical application is limited due to high manufacturing costs and low accuracy. METHODS: This work introduces a novel type of AR calibration framework that combines a Microsoft HoloLens device with a single camera registration module for surgical navigation. A camera is used to gather multi-view images of a patient for reconstruction in this framework. A shape feature matching-based search method is proposed to adjust the size of the reconstructed model. The double clustering-based 3D point cloud segmentation method and 3D line segment detection method are also proposed to extract the corner points of the image marker. The corner points are the registration data of the image marker. A feature triangulation iteration-based registration method is proposed to quickly and accurately calibrate the pose relationship between the image marker and the patient in the virtual and real space. The patient model after registration is wirelessly transmitted to the HoloLens device to display the AR scene. RESULTS: The proposed approach was used to conduct accuracy verification experiments on the phantoms and volunteers, which were compared with six advanced AR calibration methods. The proposed method obtained average fusion errors of 0.70 ± 0.16 and 0.91 ± 0.13 mm in phantom and volunteer experiments, respectively. The fusion accuracy of the proposed method is the highest among all comparison methods. A volunteer liver puncture clinical simulation experiment was also conducted to show the clinical feasibility. CONCLUSIONS: Our experiments proved the effectiveness of the proposed AR calibration method, and revealed a considerable potential for improving surgical performance.
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Realidade Aumentada , Cirurgia Assistida por Computador , Calibragem , Humanos , Imageamento Tridimensional , Imagens de FantasmasRESUMO
The identification of new diagnostic and therapeutic biomarkers might be helpful to understand molecular mechanism of cancer pathogenesis and develop anti-cancer targets. This study reported the alteration of Sodium channel 1 subunit alpha (SCNN1A) expression, its prognostic significance and biological roles in pancreatic cancer. Bioinformatics database was searched to explore the expression of SCNN1A in pancreatic cancer specimens and analysis results were further validated by qRT-PCR and Western blot assay. The correlation between SCNN1A expression and clinicopathological characteristics and its impact on survival outcome of pancreatic cancer patients were investigated using GEPIA database and Kaplan-Meier plotter. Loss- and gain-of-functional experiments in vitro were done to investigate the biological function of SCNN1A in pancreatic cancer. Bioinformatics analysis and validation experiment showed that SCNN1A was frequently overexpressed in pancreatic cancer specimens and cell lines (P < 0.001), and there were significant relevance between high SCNN1A expression and TP53 mutation (P < 0.05) as well as unfavorable prognosis of pancreatic cancer patients (HR for overall survival: 1.9, P = 0.003 and HR for disease-free survival: 1.7, P = 0.014). The silencing of SCNN1A suppressed cell proliferation, migration and invasion and induced cell apoptosis (P < 0.05), while its overexpression promoted aggressive phenotypes of pancreatic cancer cells in vitro (P < 0.05). SCNN1A possessed oncogenic function and its dysregulation could be implicated in the development and metastasis of pancreatic cancer.
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Neoplasias Pancreáticas , Sódio , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/patologia , Sódio/metabolismo , Canais de Sódio/genética , Neoplasias PancreáticasRESUMO
Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and ß subunits1-3. A tethered agonism mediated by the 'Stachel sequence' of the ß subunit has been proposed to have central roles in aGPCR activation4-6. Here we present three cryo-electron microscopy structures of aGPCRs coupled to the Gs heterotrimer. Two of these aGPCRs are activated by tethered Stachel sequences-the ADGRG2-ß-Gs complex and the ADGRG4-ß-Gs complex (in which ß indicates the ß subunit of the aGPCR)-and the other is the full-length ADGRG2 in complex with the exogenous ADGRG2 Stachel-sequence-derived peptide agonist IP15 (ADGRG2(FL)-IP15-Gs). The Stachel sequences of both ADGRG2-ß and ADGRG4-ß assume a U shape and insert deeply into the seven-transmembrane bundles. Constituting the FXφφφXφ motif (in which φ represents a hydrophobic residue), five residues of ADGRG2-ß or ADGRG4-ß extend like fingers to mediate binding to the seven-transmembrane domain and activation of the receptor. The structure of the ADGRG2(FL)-IP15-Gs complex reveals the structural basis for the improved binding affinity of IP15 compared with VPM-p15 and indicates that rational design of peptidic agonists could be achieved by exploiting aGPCR-ß structures. By converting the 'finger residues' to acidic residues, we develop a method to generate peptidic antagonists towards several aGPCRs. Collectively, our study provides structural and biochemical insights into the tethered activation mechanism of aGPCRs.
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Peptídeos , Receptores Acoplados a Proteínas G , Microscopia Crioeletrônica , Humanos , Peptídeos/metabolismo , Domínios Proteicos , Receptores Acoplados a Proteínas G/metabolismoRESUMO
RATIONALE: Pseudotumor formation after hip arthroplasty is a rare complication that can occur not only at the head-neck junction but also at the modular neck-stem junction. Dislocation is a challenging and common complication of primary and revision total hip arthroplasty compared with other complications. Similarly, the association between pseudotumors and delayed recurrent dislocation remains unclear. PATIENT CONCERNS: We report the case of a 73-year-old woman with pseudotumor formation after total hip arthroplasty combined with a modular femoral neck. A delayed recurrent dislocation occurred in this case. Approximately 4weeks after the first revision surgery, redislocation occurred. DIAGNOSIS: The patient was eventually diagnosed with delayed recurrent artificial hip dislocation combined with a periprosthetic pseudotumor of the right hip. INTERVENTIONS: During the first revision surgery, a thickened, indurated cyst measuring 8×3×8cm with a red-brown wall containing brown fluid was completely excised. A cemented stem, combined with a BIOLOX Forte ceramic head, was implanted. Approximately 4weeks after surgery, redislocation occurred, and we cemented an elevated rim liner on the acetabular component with a metal head. OUTCOMES: At the last follow-up, 49 months after revision surgery, the patient was asymptomatic with a Harris hip score of 90. The patient had a satisfactory prognosis after treatment. LESSONS: The application of the modular-neck stem should be cautiously performed, particularly for modular prostheses containing different alloys. Pseudotumors and insufficient soft-tissue tension both contribute to hip instability, which may eventually lead to delayed repeated dislocation. In addition, femoral offset must be considered. Cement-liner technology may be used for aging patients who are less active. This case report, focusing on pseudotumors and delayed recurrent dislocations, aimed to identify factors that may support this diagnosis, which is easy to miss. Consequently, it can provide further details on the treatment process and alert orthopedic surgeons to this infrequent but important cause of delayed recurrent dislocation.
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Artroplastia de Quadril , Luxação do Quadril , Prótese de Quadril , Idoso , Artroplastia de Quadril/efeitos adversos , Feminino , Colo do Fêmur , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia , Prótese de Quadril/efeitos adversos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos RetrospectivosRESUMO
PURPOSE: Facial repair surgeries (FRS) require accuracy for navigating the critical anatomy safely and quickly. The purpose of this paper is to develop a method to directly track the position of the patient using video data acquired from the single camera, which can achieve noninvasive, real time, and high positioning accuracy in FRS. METHODS: Our method first performs camera calibration and registers the surface segmented from computed tomography to the patient. Then, a two-step constraint algorithm, which includes the feature local constraint and the distance standard deviation constraint, is used to find the optimal feature matching pair quickly. Finally, the movements of the camera and the patient decomposed from the image motion matrix are used to track the camera and the patient, respectively. RESULTS: The proposed method achieved fusion error RMS of 1.44 ± 0.35, 1.50 ± 0.15, 1.63 ± 0.03 mm in skull phantom, cadaver mandible, and human experiments, respectively. The above errors of the proposed method were lower than those of the optical tracking system-based method. Additionally, the proposed method could process video streams up to 24 frames per second, which can meet the real-time requirements of FRS. CONCLUSIONS: The proposed method does not rely on tracking markers attached to the patient; it could be executed automatically to maintain the correct augmented reality scene and overcome the decrease in positioning accuracy caused by patient movement during surgery.