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BACKGROUND: In this network meta-analysis (NMA), the efficiency and safety of PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy were compared in the first-line therapy of patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: We searched research databases, conference abstracts, and trial registries and subsequently chose relevant studies and extracted dates. The NMA was conducted to estimate the efficiency and safety of the PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy on overall survival (OS), progression-free survival (PFS), overall remission rate (ORR), and adverse events (AEs). Studies were assessed for quality. Subgroup analyses were used to evaluate study heterogeneity. RESULTS: We included six randomized trials with a total of 3163 patients. Direct comparisons showed that patients who received either PD-1 inhibitors + chemotherapy (HR: 0.71, 95% CI: 0.57-0.87) or PD-L1 inhibitors + chemotherapy (HR: 0.74, 0.61-0.89) demonstrated significantly longer OS than those who received placebo + chemotherapy. The results of the NMA showed that no significant differences in OS (HR 0.96 95% CI: 0.72-1.3), PFS (HR 0.83, 95% CI: 0.51-1.4), and ORR (OR 1.3 95% CI: 0.66-2.5) were observed for PD-1 inhibitors + chemotherapy compared with PD-L1 inhibitors + chemotherapy, but the Bayesian ranking revealed that patients receiving PD-1 inhibitors + chemotherapy tended to have longer OS, PFS benefit, and better treatment response than patients receiving PD-L1 inhibitors + chemotherapy. In terms of safety, no significant difference was observed in their safety profiles. CONCLUSION: In comparison to placebo + chemotherapy, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy significantly improved survival for ES-SCLC. According to the available data, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy had equivalent efficacy and safety; however, the level of evidence of this type of comparison is limited.
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Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Metanálise em Rede , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Antígeno B7-H1/antagonistas & inibidores , Resultado do TratamentoRESUMO
Objective: The study aimed to evaluate the risk factors for the morbidity and prognosis of lung metastases (LM) in patients with newly diagnosed ovarian cancer (OC), and further explore the important role of marital status. Materials and methods: Based on the Surveillance, Epidemiology, and End Results (SEER) dataset, OC patients from 2010 and 2019 were retrospectively analyzed. Logistic regression analysis and Kaplan-Meier method were applied to evaluate the vital factors of incidence and survival outcome in LM population. Cox regression analysis was performed to identify risk factors for the prognosis of OC patients with LM. The predictive potential was showed by two established nomograms and examined by the concordance index (C-index), calibration curves, the area under the curve (AUC), decision curve analyses (DCAs) and clinical impact curves (CICs). Results: There are 25,202 eligible OC patients were enrolled in the study, the morbidity of LM at 5.61%. Multivariable logistic regression models illustrated that chemotherapy (P<0.01), surgical treatment of bilateral or more areas (P<0.01), T stage (P<0.01), N1 stage (P<0.01), bone metastasis (P<0.01), brain metastasis (P<0.01) and liver metastasis (P<0.01) were all significantly connected with LM in OC. Multivariable Cox regression analyses illustrated that unmarried, radiotherapy, elder people and positive cancer antigen 125 (CA-125) were significantly associated with shorter survival time, while chemotherapy made contributions to improve survival. Our study found that marital relationships promoted LM and was associated with the better prognosis, while unmarried patients had the opposite results. With the further development of our research, the cross-action of social, economic and psychological factors together determined the great impact of marital status on the morbidity and prognosis of OC patients combined with LM. Finally, the stability of the models was proved by internal verification. Conclusion: The population-based cohort study provides references for guiding clinical screening and individualized treatment of OC patients with LM. Under the influence of society and economy, marital status is closely related to the morbidity and prognosis of OC, which can be an important direction to explore the risk of OC lung metastasis in the future.
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BACKGROUND: Sirtuins (SIRTs) have key roles in cancer progression. However, the prognostic implications of SIRTs in breast cancer (BC) remains a subject of debate and controversy. Thus, we performed a meta-analysis to identify the precise prognostic value of SIRTs in BC patients. METHODS: Systematic literature searching was conducted in PubMed, Cochrane Library, Web of Science, and Embase databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association of SIRTs expression and survival outcomes in BC patients. RESULTS: A total of 22 original studies with 6317 patients were eligible for this meta-analysis. The results showed that in patients with BC, elevated SIRTs levels were associated with shorter overall survival (OS) and disease-free survival (DFS) both in univariate (HR = 1.56, 95% CI 1.21-2.00; HR = 1.67, 95% CI 1.32-2.12, respectively) and multivariate analysis models (HR = 2.11, 95% CI 1.48-3.00; HR = 1.70, 95% CI 1.20-2.39, respectively). Notably, further subgroup analysis revealed that overexpression of SIRT1 and SIRT6 predicted poor OS (HR = 2.65, 95% CI 1.54-4.56; HR = 2.53, 95% CI 1.64-3.90, respectively) and DFS (HR = 1.65, 95% CI 1.07-2.56; HR = 2.74; 95% CI 1.88-4.01, respectively) in BC. CONCLUSIONS: Our data has elucidated that SIRT1 and SIRT6 could serve as prognostic biomarkers for patients with BC and may contribute to refined patient management.
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Tunable broadband near-infrared (NIR)-luminescent materials play a crucial role as light sources and tunable fiber lasers in modern technologies such as high-capacity telecommunication, imaging, and remote sensing. Despite considerable effort in studying the luminescent materials doped with rare-earth or transition metal ions, it is still challenging to achieve tunable broadband emission in photonic materials, especially in glasses, for active-fiber applications. In the present work, such NIR emission is achieved by modifying oxygen-deficient structural defects (i.e., singly ionized oxygen vacancies (VOâ) in tellurium (Te)-doped germanate glass). The local glass chemistry around Te is controlled by engineering singly ionized oxygen vacancies (VOâ) in alkali-alumino-germanate glass. This enables fine-tuning of the configurations and chemical states of Te centers over a wide range of chemical states, from ionic states to neutrally charged clusters and to positively charged clusters, resulting in various intriguing luminescent behaviors (e.g., wavelength-tunable emission, great emission enhancement, bandwidth extension).
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Bismuth (Bi)-activated luminescence materials have attracted much attention for their tunable broad emissions ranging from a visible to near-infrared (NIR) region. However, it remains a challenge to regulate the Bi valence state and achieve NIR emission via a facile way. Here, we report the design and preparation of Ba3Sc4O9:Bi phosphors, which emit visible and NIR emissions simultaneously even prepared in the air condition. The self-reduction mechanism of Bi3+ species in Ba3Sc4O9 with a rigid crystal structure is illustrated based on the charge compensation model, and the coexistence of different Bi-active centers, Bi3+ for visible emission, while Bi+ and Bi0 for NIR emission, is confirmed by the spectroscopic data and X-ray photoelectron spectroscopy (XPS) analysis. The enhanced NIR emission was further achieved through controlled reducing treatment and the related mechanism has also been clarified. This work paves a new way to control bismuth valence and tune the emission of Bi-based luminescence materials for emerging photonics applications.
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Triple-negative breast cancer (TNBC) exhibits aggressive behavior and high levels of metastasis owing to its complex heterogeneous structure and lack of specific receptors. Here, tumor cell membrane (CM)-coated bismuth/manganese oxide nanoparticles (NPs) with high indocyanine green (ICG) payload up to 50.6 wt% (mBMNI NPs) for targeted TNBC therapy are constructed. The extra-high drug load Bi@Bi2 O3 @MnOx NPs (honey-comb like structure) are formed by Kirkendall effect and electrostatic attraction. After modified with CM, they can home into tumor sites precisely, where they respond to internal overexpressed glutathione (GSH), releasing Mn2+ for chemodynamic therapy (CDT) with GSH depletion, while H2 O2 degrades into O2 enabling relief of tumor hypoxia. In response to external near-infrared irradiation, mBMNI NPs intelligently generate vigorous heat and single oxygen (1 O2 ) for photothermal therapy (PTT) and photodynamic therapy (PDT) owing to high load. Importantly, O2 production and GSH consumption during the internal response reinforce external PDT, while the heat generated through PTT during the external response promotes internal CDT. The honeycomb-like structure with high ICG load and mutual reinforcement between internal and external response results in excellent therapeutic effects against TNBC.
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Nanopartículas , Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Bismuto , Linhagem Celular Tumoral , Humanos , Verde de Indocianina , Manganês , Compostos de Manganês , Óxidos , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
Due to the in situ, real-time, and non-destructive properties, mechanoluminescence (ML) crystals have been considered as intelligent stress sensors, which demonstrate potential applications such as in inner crack visualization, light source, and ultrasonic powder recording. Thereinto, it is highly expected that near-infrared (NIR) MLs can realize the visualization of inner biological stress because mechanically induced signals from them can penetrate biological tissues. However, such an energy conversion technique fails to work in biomechanical monitoring due to the limited advances of NIR ML materials. Based on those, some research groups have begun to focus on this field and initially realized this idea in vitro while related advances are still at the early stage. To advance this field, it is highly desirable to review recent advances in NIR ML crystals. In this review, to our knowledge, all the NIR ML crystals have been included in two main groups: oxysulfides and oxides. Besides, the present and emerging trends in investigation of such crystals were discussed. In all, the aim is to advance NIR ML crystals to more practical applications, especially for that of biomechanical visualization in vivo.
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Broadband near-infrared (NIR) light sources present attractive opportunities for potential applications in high-capacity telecommunication, temperature sensing, energy conversion, and NIR spectroscopy. While significant effort has been spent on materials doped with rare-earth and transition-metal ions, the achievement of these materials with ultrabroadband NIR emission and desired wavelength region remains a long-standing challenge, especially operating in the spectral region between 700 and 1300 nm. Here, such emission is developed in tellurium (Te) cluster-doped silicate glass for the first time. Furthermore, the mechanism of the NIR luminescence due to D2h-symmetric tetratellurium (Te4) clusters is identified by density functional theory (DFT) calculations. For intense luminescence, a model for the generation and stabilization of Te clusters by tailoring topological cages via adjustment of the Na2O and Al2O3 contents and by optimizing the content of the dopant is proposed. Various stable Te clusters embedded into glass exhibit intense visible (Vis) to NIR broadband luminescence (400-1300 nm) with a spectral gap of 900 nm. In a demonstration experiment, a light-emitting diode (LED) device is fabricated from Te cluster-doped glass. This study opens a new opportunity for Te cluster-doped glass as a broadband NIR light source for spectroscopy applications.
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Bismuth (Bi)-doped materials are capable of exhibiting broadband near-infrared (NIR) luminescence in 1,000-1,700 nm; driven by the potential use in lasers and broadband optical amplifiers for modern fiber communication systems, Bi-activated NIR luminescencent glasses and related devices have attracted much attention. Compared with glass systems, Bi-doped crystals as gain media usually have more regular crystal structures to produce stronger NIR signals, and developing such materials is highly desirable. Regarding the recent advances in Bi-doped NIR crystals, here, for the first time, we summarized such crystals listed as two main categories of halogen and oxide compounds. Then, by comparing the substitution site, coordination environment, emission and excitation luminescence peaks, emitting center species, and decay times of these known Bibased NIR crystals, discussion on how to design Bi-doped NIR crystals is included. Finally, the key challenges and perspectives of Bi-doped NIR crystals are also presented. It is hoped that this review could offer inspiration for the further development of Bi-doped NIR luminescent crystals and exploit its potential applications.
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Long persistent phosphors (LPPs) with ultraviolet (UV) luminescence have great potential for application in the fields of biomedicine, environmental, and catalysis. However, it is currently limited by the design and development of remarkable UV LPPs with a suitable spectral region and an ultralong afterglow decay time. Herein, we develop a new type of Bi3+-activated LiScGeO4 LPP, which exhibits bright ultraviolet-A (UVA) persistent luminescence (PersL). Because of the existence of numerous stabilized effective traps, the as-synthesized phosphors can undergo an ultralong PersL decay time far longer than 12 h. The PersL properties, effective trap depths, distributions, and types, as well as the possible mechanism for the PersL behavior of LiScGeO4:Bi3+, are comprehensively surveyed utilizing PersL excitation spectra, PersL decay analyses, thermoluminescence experiments, and X-ray photoelectron spectroscopy. This work can cover the shortage of LPPs in the UV region and also can lay the foundation for the development of more excellent UV LPPs toward versatile novel applications.
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We report a narrow linewidth and low threshold single-frequency distributed Bragg reflector (DBR) fiber laser at 1120 nm based on a short 1.5 cm long Nd-doped silica fiber which, to the best of our knowledge, is the first demonstration of a Nd-doped fiber-based single-frequency fiber laser with a wavelength greater than 1100 nm. A stable single-longitudinal-mode laser operation with a signal-to-noise ratio greater than 67 dB was verified by a scanning Fabry-Perot interferometer. The laser threshold is as low as 10 mW. The DBR fiber laser has a maximum output power of 15 mW and optical-to-optical efficiency for the launched pump power reaches more than 8%. The narrow linewidth of 71.5 kHz is obtained in such a single-frequency fiber laser (SFFL). Our result is expected to offer an exciting new opportunity to realize high-performance SFFLs above 1100 nm.
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Parkinson's disease (PD) is a complex neurodegenerative disease affected by diverse factors, and lipid droplets (LDs) are increasingly recognized as major players in PD because of their relevance to neuron activity. However, long-term dynamic changes of LDs and their relative activity remain unclear. Here, an aggregation-induced emission (AIE) probe named 2-DPAN was prepared and employed to visualize dynamic processes of LDs in a 6-hydroxydopamine model of PD for the first time, and LDs' accumulation-peak/plateau-decrease were confirmed. We further found a close relationship between LDs and variation in mitochondrial activity. Strikingly, the progression of cell death was accelerated by lipase, whereas pre-stimulation of LDs by unsaturated fatty acid-oleic acid decreased the death process by inhibiting excessive reactive oxygen species (ROS) and fatty acid production, thereby protecting mitochondria. The utilization of 2-DPAN demonstrates the importance of LDs in neuronal homeostasis, and effective tuning of LDs may prevent or inhibit PD progression.
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Bismuth (Bi)-doped materials are a new family of laser materials, and they usually exhibit extremely broad near-infrared (NIR) luminescence in 1000-1700 nm. Therefore, they can be utilized for a new generation of ultra-broadband tunable laser sources and ultra-broadband fiber amplifier. The broadband characteristics of Bi-active NIR luminescence can meet the needs of special wavelength laser sources that rare-earth-doped lasers cannot provide. However, at present, the Bi-doped NIR luminescence materials are mainly concentrated on glass, while Bi-doped NIR luminescence laser crystals are rarely reported. In this work, a novel Bi-doped crystal Sr2B5O9Cl:Bi is reported with NIR luminescence, which exhibits broadband absorption in ultraviolet and visible regions, and can produce ultra-broadband from red to NIR luminescence covering 600-1600 nm. The results of excitation, emission spectra, and fluorescence lifetime show that the Sr2B5O9Cl:Bi crystal contains three different Bi-active NIR emission centers. This work could enrich our understanding on Bi NIR emission behaviors in crystals. And this material provides a possibility for the development of a new laser source.
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[This corrects the article DOI: 10.1038/s41377-018-0007-z.].
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The fiber laser in the range of 900-1000 nm is essential to generate the blue fiber laser through frequency doubling for the laser display, laser underwater communications, and laser lighting. Yet, the well-developed three-level Yb-doped fiber laser can only realize the blue-green fiber laser at around 490 nm, which is far from the pure blue area (450 nm). To further achieve the pure blue fiber laser, the Nd-doped fiber has emerged as a proper choice to realize a shorter wavelength laser (<920 nm) through the F3/24âI9/24 transition of Nd3+. Here, based on the facile "melt-in-tube" (MIT) method, a novel Nd-doped high alumina and yttria glass @ silica glass hybrid fiber was successfully prepared using the Nd:YAG crystal as the precursor core. The crystal core converts to the amorphous glass state after the drawing process, as evidenced by Raman spectra. The gain coefficient at 915 nm of the hybrid fiber reaches 0.4 dB/cm. Further, the laser oscillation at 915 nm with over 50 dB signal-to-noise ratio was realized by a short 3.5 cm gain fiber. Our results indicate that MIT is a feasible strategy to produce novel fiber for generating fiber laser at special wavelengths.
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Computer tomography (CT) and magnetic resonance imaging (MRI) are noninvasive cancer imaging methods in clinics. Hence, a material that enables MRI/CT dual-modal imaging-guided therapy is in high demand. Currently, the available materials lack active tumor targeting, deep tumor penetration, and ultralong tumor retention and may lose their imaging elements. To overcome these drawbacks, herein, nanoparticles (NPs) were deveopled by integrating an MRI contrast-enhancing chelated gadolinium (Gd) complex within a doxorubicin (DOX)-loaded protective silica shell as well as a CT imaging/photothermal biocompatible bismuth (Bi) nano-core, which surface-displayed an MCF-7 breast tumor-homing peptide (AREYGTRFSLIGGYR, termed AR); we found that the resultant NPs AR-Bi@SiO2-Gd/DOXNPs could home to and penetrate deep into the tumors with the unexpected ultralong retention of at least 14 days (as determined by CT/MRI imaging) and the tumor retention half-life of 104.5 h (as determined by ICP-MS analysis) under the guidance of the AR peptide. These NPs can be further used to image tumors with significantly increased sharp contrasts via both CT and MRI, which are much better than the commercial standard contrast agents; moreover, they significantly inhibit tumor growth via the synergistic action of both Bi-enabled photothermal therapy and DOX-induced chemotherapy. The NPs are cleared by the spleen, liver and kidney and then excreted from the body along with faeces and urine. The precise tumor targeting and ultralong tumor retention of these unique NPs would enable both precise tumor detection for early diagnosis and signal-persistent tumor tracking for monitoring the treatment with only a single injection of these NPs.
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Narrow band red-emitting Mn4+-doped fluoride phosphor is an essential red component of modern white-light-emitting-diode (WLED) devices. Its luminescence has sensitivity to structure and influences the performance of WLED. In this paper, we report a high-performance Mn4+ phosphor based on a new heterodialkaline fluorogermanate, CsNaGeF6:Mn4+. As determined by the single-crystal X-ray diffraction analysis, the CsNaGeF6 compound crystallizes in the orthorhombic crystal system with space group Pbcm (No. 57). Under excitation by 360 and 470 nm photons, CsNaGeF6:Mn4+ emits intense red light near 630 nm with a high quantum yield of 95.6%. The electronic energy levels of the Mn4+ ion in Cs2GeF6, Na2GeF6, and CsNaGeF6 are calculated using the exchange charge model of crystal-field theory. The local Mn4+ environment inducing different zero-phonon-line emissions in the structures is probed by electron paramagnetic resonance. The Mn4+-doped heterodialkaline fluorogermanate CsNaGeF6:Mn4+ exhibits broader emission as a result of the lowest symmetry. It has higher quantum yield than Na2GeF6:Mn4+ and higher spectral luminous efficacy than Cs2GeF6:Mn4+. Given the good thermal stability and efficient luminescence, a prototype warm-WLED device with a color rendering index of 92.5, a correlated color temperature of 3783 K, and a luminous efficacy of 176.3 lm/W has been fabricated by employing the CsNaGeF6:Mn4+ phosphor as the red component. Our results not only reveal that a high-performance Mn4+ red phosphor is achieved through cationic substitutions but also construct a relationship of performance-structure to guide the design of Mn4+ phosphors in the future.
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We report an unusual thermal response of tellurium (Te) near-infrared (NIR) luminescence in phosphate laser glass, where the luminescence first increases and then decreases with heat-treatment temperatures increasing from 250°C to the glass transition temperature (Tg). This is followed by a distinct revival of Te NIR luminescence at temperatures above Tg. This result differs from the scenario in conventional rare-earth (Er3+, Nd3+, and Yb3+)-doped phosphate glasses, where the rare-earth NIR emission decreases with increasing heat-treatment temperature. The difference may originate from conversion between Te4 and other Te species, which depends on the evolution of the glass structure and molecular motion during the reheating processes, leading to unusual thermal response of Te NIR luminescence. The increase in Te4 clusters enhances Te NIR emission, indicating that Te NIR luminescence is assigned to the Te4 cluster, in contrast to previous studies. Heating and cooling cycles between 50°C and 250°C reveal strong dependence of the thermal degradation on glass structure. Te-doped phosphate laser glass with zero thermal degradation can be realized by stabilizing NIR luminescence center Te4 by adjusting the glass structure with reduced network crosslinking. The superior optical performance has been confirmed in our previous study that the NIR luminescence properties can be well maintained in Te-doped fiber. The findings indicate that Te-doped phosphate glass with unusual thermal responses can potentially be used in fiber laser devices.
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Despite its 5-year event-free survival rate increasing to 60-65% due to surgery and chemotherapy, osteosarcoma (OS) remains one of the most threatening malignant human tumors, especially in young patients. Therefore, a new approach that combines early diagnosis with efficient tumor eradication and bioimaging is urgently needed. Here, a new type of mesoporous silica-coated bismuth sulfide nanoparticles (Bi2 S3 @MSN NPs) is developed. The well distributed mesoporous pores and large surface areas hold great promise for drug protection and encapsulation (doxorubicin (DOX), 99.85%). Moreover, the high photothermal efficiency of Bi2 S3 @MSNs (36.62%) offers great possibility for cancer synergistic treatment and highly near-infrared-triggered drug release (even at an ultralow power density of 0.3 W cm-2 ). After covalently conjugated to arginine-glycine-aspartic acid (RGD) peptide [c(RGDyC)], the NPs exhibit a high specificity for osteosarcoma and finally accumulate in the tumor cells (tenfold more than peritumoral tissues) for computed tomography (CT) imaging and tumor ablation. Importantly, the synergistic photothermal therapy-chemotherapy of the RGD-Bi2 S3 @MSN/DOX significantly ablates the highly malignant OS. It is further proved that the superior combined killing effect is achieved by activating the mitochondrial apoptosis pathway. Hence, the smart RGD-Bi2 S3 @MSN/DOX theranostic platform is a promising candidate for future applications in CT monitoring and synergistic treatment of malignant tumors.