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Inferring prospective outcomes and updating behavior are prerequisites for making flexible decisions in the changing world. These abilities are highly associated with the functions of the orbitofrontal cortex (OFC) in humans and animals. The functional specialization of OFC subregions in decision-making has been established in animals. However, the understanding of how human OFC contributes to decision-making remains limited. Therefore, we studied this issue by examining the information representation and functional interactions of human OFC subregions during inference-based decision-making. We found that the medial OFC (mOFC) and lateral OFC (lOFC) collectively represented the inferred outcomes which, however, were context-general coding in the mOFC and context-specific in the lOFC. Furthermore, the mOFC-motor and lOFC-frontoparietal functional connectivity may indicate the motor execution of mOFC and the cognitive control of lOFC during behavioral updating. In conclusion, our findings support the dissociable functional roles of OFC subregions in decision-making.
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BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is a disease of the optic nerve, but its effect on brain network topology is still unclear.This study aimed to investigate brain network alterations in NAION patients and to explore their relationship with functional impairment. METHODS: Resting-state functional MRI data were collected from 23 NAION patients and 23 matched healthy control subjects.We used graph theory analysis to investigate the global and nodal network topological properties,and network-based statistical (NBS) methods were used to explore intergroup differences in functional connectivity (FC) strength. RESULTS: Compared to the control group, NAION patients had lower global efficiency, normalized clustering coefficient and small-world values and higher characteristic path length (P < 0.05). In the hub distributions of functional networks, the NAION group had one hub region disappearing and four hub regions appearing in nodal degree centrality (Dc), and two hubs disappearing and one hub region appearing in nodal betweenness centrality (Bc). The NAION group also had enhanced brain FC primarily associated with the frontal, prefrontal, parietal lobes and cerebellum. Furthermore, the right temporal pole, superior temporal gyrus (r = -0.424), the right inferior temporal gyrus (r = -0.414), the right cerebellar lobule â ¥ (r = 0.450), and the left cerebellar lobule crus â (r = 0.584) were significantly correlated with clinical severity. CONCLUSION: NAION patients show disruption and redistribution of FC in specific regions of the brain network, which may be associated with visual impairment.
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Neuropatia Óptica Isquêmica , Humanos , Neuropatia Óptica Isquêmica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Lobo TemporalRESUMO
BACKGROUND: Onlay bone grafting is considered highly reliable for reconstructing severe horizontal bone defects. A critical problem is how to achieve precise position of the bone block to control alveolar ridge dimensions. This research aims to establish a digital workflow for prosthetically oriented onlay bone grafting and evaluate its accuracy and efficiency. METHODS: This prospective pilot study investigated eight patients who required implant restoration in the esthetic area with horizontal alveolar bone defects. The workflow includes preoperative virtual planning, design and manufacture of patient-specific templates, bone grafting surgery, and implant insertion. Primary outcomes were graft accuracy, defined by root mean square estimate (RMSE) values between preoperatively designed and actual implanted outer contours of bone blocks. Secondary outcomes were bone graft and implant success rates. Besides, the surgeons used the visual analog scale (VAS) to rate the intuitiveness, ease of understanding, and helpfulness of the workflow. RESULTS: No bone grafts or implants failed in any of the eight patients, resulting in a 100% success rate. The RMSE values between the preoperative design and the implanted outer contour of bone blocks were 0.41 ± 0.15 mm. The digital approach showed advantages in intuitiveness (9.3 ± 0.5), understanding (9.0 ± 0.5), and helpfulness (8.4 ± 1.1) according to surgeons' VAS scores. CONCLUSIONS: A digital workflow provided encouraging results, in terms of accuracy and efficacy, for horizontal bone augmentation. TRIAL REGISTRATION: This study was registered in the National Clinical Trials Registry in 16/02/2023 under the identification number ChiCTR2300068361.
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Aumento do Rebordo Alveolar , Implantes Dentários , Humanos , Transplante Ósseo/métodos , Projetos Piloto , Estudos Prospectivos , Estudos de Viabilidade , Fluxo de Trabalho , Implantação Dentária Endóssea , Aumento do Rebordo Alveolar/métodosRESUMO
OBJECTIVE: Paclitaxel (P) is a standard second-line chemotherapy in the treatment of advanced gastric cancer. This study compared the clinical outcome of a paclitaxel plus raltitrexed (RP) regimen as second-line treatment in metastatic gastric cancer (MGC) patients. METHODS: An open, randomized, multi-center phase II clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP [raltitrexed (3 mg/m2 on day 1) and paclitaxel (135 mg/m2 on day 1 every 3 weeks)] or P [paclitaxel (135 mg/m2 on day 1 every 3 weeks)] as 2nd-line chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), and safety. RESULTS: PFS had a tendency to be prolonged with RP compared to P (2.7 months vs. 1.7 months; P = 0.148). OS was also prolonged with RP compared to P (10.2 months vs. 6.1 months; P = 0.140). The ORR was equal in the RP and P groups (6.8% and 4.0%; P = 0.72). The disease control rate (DCR) in the RP and P groups was 56.2% and 36.0%, respectively. Grade 3-4 treatment-related adverse events occurred in 36.2% (RP) and 28.2% (P) of patients. Frequent grade 3-4 toxicities for RP and P were neutropenia (11.0% and 4.0%), anemia (1.4% and 4.0%), and thrombocytopenia (1.4% and 5.3%), and all grades of peripheral neurotoxicity (12.3% vs. 17.3%). All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels (27.4% and 14.1%). Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement, the OS of the RP regimen was longer (P = 0.05). CONCLUSIONS: Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS, especially among patients with ascites or peritoneal involvement, which warrants confirmation using larger sample studies.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Paclitaxel , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Ascite/induzido quimicamente , Ascite/tratamento farmacológico , Adenocarcinoma/tratamento farmacológicoRESUMO
PURPOSE: To compare clinical and histological outcomes of sinus augmentation performed immediately or 3 months after pseudocyst removal through a prospective randomized controlled study. MATERIALS AND METHODS: In total, 33 sinus augmentation procedures were performed in 31 patients. Augmentation was performed either immediately after pseudocyst removal (one-stage intervention) or after 3 months (two-stage intervention). Six months postoperatively, bone specimens were harvested, and histomorphometric analysis was performed as primary outcome. Data were recorded and evaluated for implant survival rates, marginal bone resorption, complication rate, and patient-centered outcomes (visual analogue scale [VAS]). RESULTS: There were no baseline differences between groups or dropouts. Twelve biopsies obtained for histomorphometric analysis showed that delayed sinus augmentation, when compared to immediated led to a 1.1% increased mineralized bone ratio (95% confidence interval [CI]: -15.9 to 13.7). Graft leakage and acute sinusitis occurred in one patient in the one-stage group, none in the two-stage group. No pseudocyst recurrence was observed until the end of 1-year follow-up. Median VAS scores for overall acceptance were significantly increase of 1.4 (95% CI: 0.3-2.56) in immediate group. The degree of post-operative discomfort was not significantly different, although an increase of VAS (0.52, 95% CI: -0.32 to 1.37) was observed in delay group. CONCLUSIONS: Both procedures of sinus augmentation immediately and 3 months after pseudocyst removal could obtain comparable histological outcomes and had low complication rates. Patients who underwent the one-stage procedure had a short treatment course and high satisfaction rates, but this procedure is technically challenging to perform. This clinical trial was not registered prior to participant recruitment and randomization. The clinical trial registration number is ChiCTR2200063121. The hyperlink is as follows: https://www.chictr.org.cn/showproj.html?proj=172755.
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Substitutos Ósseos , Cistos , Levantamento do Assoalho do Seio Maxilar , Humanos , Implantação Dentária Endóssea , Levantamento do Assoalho do Seio Maxilar/métodos , Estudos Prospectivos , Seio Maxilar/cirurgia , Transplante Ósseo/métodos , Cistos/patologiaRESUMO
Purpose: To evaluate the implant survival and the prevalence of biologic and mechanical complications in edentulous patients restored with complete-arch implant-supported fixed dental prostheses (IFDPs). Materials and Methods: Patients restored with complete-arch screw-retained IFDPs between January 2012 and December 2019 with a minimum 2-year follow-up were included. Outcome measures were cumulative survival rate (CSR) for implants and prostheses, biologic complications, and mechanical complications. A generalized estimating equation model was used to estimate potential risk factors for mechanical complications. Patient satisfaction was investigated using a standardized questionnaire. Results: A total of 44 prostheses supported by 268 implants in 30 patients were included for a mean duration of 4.8 years (range: 2 to 9 years). Eighteen of the prostheses were zirconia-ceramic (group ZC), and 26 were titanium-ceramic (group TC). The CSR for the implants and IFDPs was 99.3% (95% CI: 98.2% to 100.3%) and 92.5% (95% CI: 84.2% to 100.8%), respectively. The most common biologic complication was peri-implant mucositis (4.5%), followed by peri-implantitis (3.0%). The most common mechanical complication was ceramic chipping (45.5%), followed by crown debonding (13.6%) and framework fracture (4.5%). There was no significant difference in the prevalence of complications between groups TC and ZC (P > .050). The presence of cantilever (OR = 5.54, P = .048) and maxillary arch (OR = 5.94, P = .041) were significantly associated with mechanical complications. Patient satisfaction scores were generally high, but some continued to be bothered by speech problems (13.6%). Conclusion: Complete-arch IFDPs presented reliable clinical outcomes for edentulous patients with a high implant survival rate and a high level of patient satisfaction. However, a high incidence of mechanical complications occurred in the long term.
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Produtos Biológicos , Implantes Dentários , Boca Edêntula , Peri-Implantite , Humanos , Estudos Retrospectivos , Seguimentos , Prevalência , Falha de Restauração Dentária , Prótese Dentária Fixada por Implante/efeitos adversosRESUMO
Osteoarthritis (OA) is a degenerative disease that causes chronic pain and joint swelling and even disables millions of patients. However, current non-surgical treatment for OA can only relieve pain without obvious cartilage and subchondral bone repair. Mesenchymal stem cell (MSC)-secreted exosomes have promising therapeutic effects on knee OA, but the efficacy of MSC-exosome therapy is not well determined, and the mechanisms involved are still unclear. In this study, we isolated dental pulp stem cell (DPSC)-derived exosomes by ultracentrifugation and determined the therapeutic effects of a single intra-articular injection of DPSC-derived exosomes in a mice knee OA model. The results showed that the DPSC-derived exosomes effectively improved abnormal subchondral bone remodeling, inhibited the occurrence of bone sclerosis and osteophytes, and alleviated cartilage degradation and synovial inflammation in vivo. Moreover, transient receptor potential vanilloid 4 (TRPV4) was activated during the progression of OA. Enhanced TRPV4 activation facilitated osteoclast differentiation, and TRPV4 inhibition blocked this process in vitro. DPSC-derived exosomes repressed osteoclast activation in vivo by inhibiting TRPV4 activation. Our findings demonstrated that a topical, single injection of DPSC-derived exosomes is a potential strategy for knee OA treatment, and that the exosomes regulated osteoclast activation by TRPV4 inhibition, which may act as a promising target for clinical OA treatment.
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Cartilagem Articular , Exossomos , Osteoartrite do Joelho , Animais , Camundongos , Osteoartrite do Joelho/metabolismo , Canais de Cátion TRPV/metabolismo , Osteoclastos , Exossomos/metabolismo , Polpa Dentária , Modelos Animais de Doenças , Células-Tronco , Cartilagem Articular/metabolismo , Condrócitos/metabolismoRESUMO
Blue emitting nitrogen-doped carbon dots were synthesized using citric acid and urea through the hydrothermal method, and the fluorescence quantum yield was 35.08%. We discovered that N-CDs featured excellent robust fluorescence stability and chemical resistance. For metronidazole detection, our N-CDs exhibited quick response time, high selectivity and sensitivity, and low cytotoxicity. Specifically, our N-CDs could detect metronidazole in the linear range of 0-179 µM, and the LOD was 0.25 µM. Furthermore, metronidazole efficaciously quenches the fluorescence of N-CDs, possibly owing to the inner filter effect. Lastly, we have employed our N-CDs to detect metronidazole in commercial metronidazole tablets with high accuracy. Overall, the newly prepared fluorescence sensor, N-CDs, demonstrated a huge potential to detect metronidazole in a simple, efficient, sensitive, and rapid manner.
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To investigate morphological changes of the total and inferior part of the maxillary sinus following Le Fort I osteotomy. 21 skeletal class II and 49 skeletal III patients who underwent orthognathic surgery were enrolled in this retrospective study. Cone-beam computed tomography taken before (T1) and 6 to 24 months after (T2) orthognathic surgery were imported into Mimics 20.0 software to analyze morphological changes of the total and inferior part of the maxillary sinus. Volume of the whole maxillary sinus was significantly reduced after surgery ( P ≤0.008), while the volume of the inferior part of the maxillary sinus was significantly greater than before surgery ( P ≤0.004). Maxillary sinus floor moved occlusally after Le Fort I osteotomy. Movement in the pitch direction of the posterior maxilla affected the state of the maxillary sinus mucosa after orthognathic surgery. Le Fort I osteotomy exerts a significant impact on the morphology of the total and inferior part of the maxillary sinus.
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Seio Maxilar , Levantamento do Assoalho do Seio Maxilar , Humanos , Seio Maxilar/cirurgia , Estudos Retrospectivos , Osteotomia de Le Fort/métodos , Maxila/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos , Osteotomia MaxilarRESUMO
This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. Background: Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. Methods: In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. Results: Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). Conclusion: TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.
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PURPOSE: To identify the impact of residual bone height on 5-year implant survival and prosthetic complication rates in patients who underwent maxillary sinus grafting. MATERIALS AND METHODS: A total of 87 consecutive patients were treated with 104 lateral approach maxillary sinus floor augmentation procedures with 100% deproteinized bovine bone and received 169 implants. The analysis considered patient age, sex, time of implant placement, and residual bone height. Patients with < 3 mm residual bone height were assigned to the study group; otherwise, they were placed in the control group. RESULTS: The mean follow-up was 68.2 months (0 to 103 months). The mean residual bone height was 1.8 mm in the study group and 4.1 mm in the control group. The 5-year implant survival and prosthetic complication rates were, respectively, 97.4% and 8.0% in the study group and 100% and 12.5% in the control group. Residual bone height, sex, age, and time of implant placement were not significant factors for the 5-year implant survival or prosthetic complication rate. The lateral bone wall was significantly thinner in the study group. The grafted bone height reduction was significantly different at 6 months and 2 years postoperation in both groups, but there was no difference in the change in grafted bone height reduction over time between the two groups. CONCLUSION: A residual bone height < 3 mm did not impact the survival rates of implants placed in grafted maxillary sinuses or the prosthetic complication rate after 5 years of functional loading.
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Aumento do Rebordo Alveolar , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Animais , Bovinos , Implantação Dentária Endóssea/métodos , Humanos , Seio Maxilar/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Taxa de SobrevidaRESUMO
PURPOSE: To primarily evaluate the dimensional changes of bone and soft tissue following ridge augmentation in compromised molar regions. The secondary objective was to evaluate the histologic composition of augmented sites. MATERIALS AND METHODS: The study included 27 patients who underwent augmentation of extraction sites with grafts covered by a collagen membrane. CBCT was taken immediately after augmentation (T2) and after 8 months of healing, before implant placement (T3). The width and height of the extraction sites were recorded at extraction (T1) and reentry surgery (T4). A histomorphometric analysis was performed. Data were evaluated in terms of bone crest level, implant survival rates, and change in mucogingival junction. RESULTS: According to clinical measurement, horizontal and vertical bone gain was 10.15 ± 1.00 mm and 8.80 ± 1.86 mm, respectively. Radiographic measurement showed that the horizontal width changes were 1.46 ± 0.52 mm, 0.98 ± 1.29 mm, and 1.29 ± 0.82 mm, respectively, at 1, 3, and 5 mm apical to the crestal level. Vertical bone change was 2.34 ± 0.90 mm in the center of the socket. Histomorphometric analysis showed that percentages of mineralized bone, nonmineralized tissue, and bone substitute were 32.31% ± 13.25%, 25.36% ± 12.24%, and 42.34% ± 9.54%, respectively. The mucogingival junction shift was 0.6 ± 1.1 mm. Implant survival rates and crestal bone resorption were 100% and 0.78 ± 0.58 mm, respectively, after 1 year of loading. CONCLUSION: Ridge augmentation can be performed successfully to manage extraction sockets. Membrane coverage combined with primary wound closure could be conducive to new bone regeneration and peri-implant tissue health.
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Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/cirurgia , Processo Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Humanos , Estudos Prospectivos , Extração Dentária , Alvéolo Dental/patologia , Alvéolo Dental/cirurgiaRESUMO
BACKGROUND: mTOR pathway is known to promote cancer malignancy and influence cancer immunity but is unknown for its role in immune checkpoint inhibitors (ICI) therapy. METHODS: Using Memorial Sloan-Kettering Cancer Center dataset (MSKCC), we extracted mTOR pathway gene mutations for stepwise Cox regression in 1661 cancer patients received ICI. We associated the mutation of the gene signature resulted from the stepwise Cox regression with the 1661 patients' survival. Other 553 ICI-treated patients were collected from 6 cohorts for validation. We also performed this survival association in patients without ICI treatment from MSKCC as discovery (n = 2244) and The Cancer Genome Atlas (TCGA) as validation (n = 763). Pathway enrichment analysis were performed using transcriptome profiles from TCGA and IMvigor210 trial to investigate the potential mechanism. RESULTS: We identified 8 genes involved in mTOR pathway, including FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1, mTOR, and RPTOR, resulted from stepwise Cox regression in discovery (n = 1661). In both discovery (n = 1661) and validation (n = 553), the mutation of the 8-gene signature was associated with better survival of the patients treated with ICI, which was independent of tumor mutation burden (TMB) and mainly attributed to the missense mutations. This survival association was not observed in patients without ICI therapy. Intriguingly, the mutation of the 8-gene signature was associated with increased TMB and PD1/PD-L1 expression. Immunologically, pathways involved in anti-tumor immune response were enriched in presence of this mutational signature in mTOR pathway, leading to increased infiltration of immune effector cells (e.g., CD8 + T cells, NK cells, and M1 macrophages), but decreased infiltration of immune inhibitory M2 macrophages. CONCLUSIONS: These results suggested that mTOR pathway gene mutations were predictive of better survival upon ICI treatment in multiple cancers, likely by its association with enhanced anti-tumor immunity. Larger studies are warranted to validate our findings.
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Inibidores de Checkpoint Imunológico , Neoplasias , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Mutação/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Serina-Treonina Quinases TOR/genéticaRESUMO
Transitive inference (TI) is a critical capacity involving the integration of relevant information into prior knowledge structure for drawing novel inferences on unobserved relationships. To date, the neural correlates of TI remain unclear due to the small sample size and heterogeneity of various experimental tasks from individual studies. Here, the meta-analysis on 32 fMRI studies was performed to detect brain activation patterns of TI and its three paradigms (spatial inference, hierarchical inference, and associative inference). We found the hippocampus, prefrontal cortex (PFC), putamen, posterior parietal cortex (PPC), retrosplenial cortex (RSC), supplementary motor area (SMA), precentral gyrus (PreCG), and median cingulate cortex (MCC) were engaged in TI. Specifically, the RSC was implicated in the associative inference, whereas PPC, SMA, PreCG, and MCC were implicated in the hierarchical inference. In addition, the hierarchical inference and associative inference both evoked activation in the hippocampus, medial PFC, and PCC. Although the meta-analysis on spatial inference did not generate a reliable result due to insufficient amount of investigations, the present work still offers a new insight for better understanding the neural basis underlying TI.
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Imageamento por Ressonância Magnética , Lobo Parietal , Aminoacridinas , Giro do Cíngulo , Humanos , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologiaRESUMO
BACKGROUND: The prosthetic emergence profile design might be an important factor in postsurgical mucosal recession etiology. Therefore, a restorative buccal emergence profile designed correctly might reduce gingival margin recession. PURPOSE: To compare the marginal gingival level and the width/height (W/H) ratio between two profile configurations of single implant-supported restorations at molar sites. MATERIALS AND METHODS: Twenty-one patients requiring a single mandibular molar tooth replacement with supracrestal mucosal thickness ≥2 mm were recruited and randomly assigned to a prosthesis buccal emergence profile design based on the buccal mucosal W/H ratio (Test Group) or maintained the original emergence profile of the healing abutment (Control Group). Assessments were made before delivery of the definitive restoration (T0), at prosthesis placement (T1), one (T2), and 12 (T3) months after loading. The gingival margin level change (â³GM), initial emergence angle, buccal mucosal W/H ratio, marginal bone loss (MBL), implant failure, and complications were assessed. RESULTS: The gingival recession in the test group (0.13 ± 0.32 mm) was significantly lower than in the control group (0.63 ± 0.38 mm) at T3 (p = 0.006). The initial emergence angle in the test group (31.4 ± 7.22 degrees) was significantly lower than the control group (40.0 ± 7.60 degrees) (p = 0.025). The W/H ratio in the test group at T2 was significantly higher than at T0 but remained stable thereafter. The W/H ratio presented a continued rising trend in the control group. CONCLUSIONS: When the initial supracrestal soft tissue thickness was ≥2 mm, a restorative emergence profile based on the W/H ratio significantly reduced gingival margin recession. An emergence angle of 32.4 degrees showed better behavior in maintaining the gingival margin than 40 degrees. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR190002210.
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Implantes Dentários para Um Único Dente , Implantes Dentários , Retração Gengival , Gengiva/cirurgia , Retração Gengival/etiologia , Humanos , Dente Molar , Mucosa Bucal/cirurgiaRESUMO
In our study, a unique ratiometric fluorescent sensor for the rapid detection of arginine (Arg) and acetaminophen (AP) was constructed by the integration of blue fluorescent N-CDs and yellowish-green fluorescent calcein. The N-CD/calcein ratiometric fluorescent sensor exhibited dual emission at 435 and 519 nm under the same excitation wavelength of 370 nm, and caused potential Förster resonance energy transfer (FRET) from N-CDs to calcein. When detecting Arg, the blue fluorescence from the N-CDs of the N-CD/calcein sensor was quenched by the interaction of N-CDs and Arg. Then, the fluorescence of our sensor was recovered with the addition of AP, possibly due to the stronger association between AP and Arg, leading to the dissociation of Arg from N-CDs. Meanwhile, we observed an obvious fluorescence change from blue to green, then back to blue, when Arg and AP were added, exhibiting the "on-off-on" pattern. Next, we determined the detection limits of the N-CD/calcein sensor to Arg and AP, which were as low as 0.08 µM and 0.02 µM, respectively. Furthermore, we discovered that the fluorescence changes of the N-CD/calcein sensor were only responsible for Arg and AP. These results suggested its high sensitivity and specificity for Arg and AP detection. In addition, we have successfully achieved its application in bovine serum samples, indicating its practicality. Lastly, the logic gate was generated by the N-CD/calcein sensor and presented its good reversibility. Overall, we have demonstrated that our N-CD/calcein sensor is a powerful sensor to detect Arg and AP and that it has potential applications in biological analysis and imaging.
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BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.
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Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Oxaliplatina , Oxaloacetatos , Estudos Prospectivos , Qualidade de Vida , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: It is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases. METHODS: Colon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744. RESULTS: Between April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9-181.1) in group A and 196 days (95% CI: 96.5-295.5) in group B (HR: 0.930 95% CI: 0.589-1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3. CONCLUSION: PTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.
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BACKGROUND: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. METHODS: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. RESULTS: A total of 172 patients with mCRC were randomly treated with FOLFIRI (n = 88) or irinotecan (n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911-1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3-4 neutropenia (47.7% versus 21.7%). CONCLUSION: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764.
RESUMO
STATEMENT OF PROBLEM: Screw- and cement-retained prostheses (SCRPs) may be contaminated during fabrication in a dental laboratory, leading to mechanical and biological complications related to the implant treatment. Studies that explored methods to efficiently and conveniently clean and disinfect SCRPs are sparse. PURPOSE: The purpose of this clinical study was to compare the efficiency of 3 methods to remove contaminants and microorganisms present on the surface of an SCRP. MATERIAL AND METHODS: Forty-eight 1-unit SCRPs fabricated in a dental laboratory were randomly divided into 3 groups: wiping, soaking, or ultrasonic cleaning. The presence of contaminants was determined by scanning electron microscopy, and microbial cells were cultured before and after treatment. Bacterial colony-forming units (CFUs) on the surface of the SCRPs and contamination density at the implant-abutment interface and emergence profile area were assessed. Statistical tests including ANCOVA were used to compare the efficiency of different methods before and after treatment (α=.05). RESULTS: Significant differences in contamination density were noted during the treatment at the implant-abutment interface and at the emergence profile area in the 3 groups (P<.05), but no significant differences were observed in the number of CFUs (P>.05). There were significant differences among the 3 methods for cleaning efficiency both at the implant-abutment interface (P=.023) and the emergence profile area (P=.038). At the implant-abutment interface, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the soaking group (P=.007), whereas at the emergence profile area, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the wiping group (P=.019) and the soaking group (P=.048). CONCLUSIONS: All 3 treatment methods reduced contaminants on the SCRP surface, but ultrasonic cleaning yielded the most favorable results. However, none of the methods provided additional disinfection for SCRPs previously disinfected by ozone and UV in a dental laboratory.