Comparison of survival outcomes between clinical trial participants and non-participants of patients with advanced non-small cell lung cancer: A retrospective cohort study.

Background: Clinical trials for advanced non-small cell lung cancer (NSCLC) have been conducted extensively. However, the effect of participation in clinical trials on survival outcomes remains unclear. This study aimed to assess whether participation in clinical trials was an independent prognostic factor for survival in patients with advanced NSCLC. Methods: We analyzed the medical records of patients aged ≥18 years who were newly diagnosed with stage IIIB or IV NSCLC and received chemotherapy or immunotherapy from September 2016 to June 2020 in this retrospective cohort study. To reduce the impact of confounding factors, propensity score matching (PSM) was performed. The Kaplan-Meier method and log-rank test were used to calculate and compare the overall survival (OS) and progression-free survival (PFS) of the patients. Finally, Cox proportional hazards regression was employed to examine the correlation between clinical trial participation and survival outcomes. Results: The study enrolled 155 patients in total, of which 62 (40.0 %) patients participated in NSCLC clinical trials. PSM identified 50 pairs of patients in total. The median PFS and OS of clinical trial participants and non-participants were 17.2 vs. 13.9 months (p = 0.554) and 32.4 vs. 36.5 months (p = 0.968), respectively. According to the results of multivariate Cox proportional hazards regression analysis, clinical trial participation was not an independent prognostic factor for advanced NSCLC patients (HR: 0.89, 95 % CI: 0.50-1.61; p = 0.701). Conclusions: The clinical trial participants with advanced NSCLC displayed similar survival outcomes compared with the non-participating patients in this cohort.

Functionalized Ag/Fe-MOFs nanocomposite as a novel endogenous redox mediator for determination of α2,6-sialylated glycans in serum.

The development of a novel signal amplification system is described for sensitive determination of α2,6-sialylated glycans (α2,6-sial-Gs), an important prognostic tumor biomarker. First, Fe-based metal-organic frameworks (Fe-MOFs) with silver nanoparticles (AgNPs) decorated onto the outer surface were designed and synthesized with controlled octahedron structures. The new Ag/Fe-MOFs nanocomposite possessed strong conductivity and a large surface area to carry more nanoprobes. To connect the Ag/Fe-MOFs nanocomposite with more groups, the nanocomposite was functionalized by -COOH with SH-PEG-COOH to bind with an α2,6-sial-Gs catcher, M-APBA, via -CONH- bonds. More importantly, the Ag/Fe-MOFs also exhibited an excellent endogenous redox mediator property to produce electrons, which is the fundamental mechanism underlying amplification of an electronic signal. A gold electrode was used to accelerate electron transfer and immobilize the α2,6-sial-Gs lectin (SNA). After the sandwich-type catcher recognition (SNA/α2,6-sial-Gs/M-APBA), the current peak response was provoked in the process of oxidizing AgNPs to Ag+ in the forward anodic potential sweep, while Cl- in a PBS solution was transferred into Ag+ to maintain charge neutrality. Optimized particles were employed for direct fabrication of the sandwich-type affinity biosensor, which was found to show a linear detection range from 1 fg mL-1 to 1 ng mL-1 with a detection limit of 0.09 fg mL-1. Furthermore, the biosensor exhibited excellent specificity and stability, indicating that such a novel nanobiotechnology platform can be used to initiate potential utility for monitoring biomarkers in serum. (A)Schematic presentation of synthesis and surface modification of Ag/Fe-MOFs. The new Ag/Fe-MOFs nanocomposite possessed commendable conductivity and large surface area to carry more nanoprobe; after functionalizing the Ag/MOFs with SH-PEG-COOH, the functionalized endogenous redox mediator (c-Ag/MOFs) realized the possibility that can connect with the biological catcher. (B) Schematic diagram of electrode construction for detecting α2,6-sialylated glycans (α2,6-sial-Gs). By using the c-Ag/Fe-MOFs functional endogenous redox mediator, we successfully implemented the electrochemical detection of α2,6-sial-Gs.

Au@BSA microspheres-luminol and a novel luminescent Zeolitic Imidazolate Framework were used for potential-resolved electrochemiluminescence to detect dual targets.

Here, a novel electrochemiluminescence biosensor based on potential-resolved strategy was firstly prepared for the detection of dual targets α2,3-sialylated glycans and α2,6-sialylated glycans. This is the first time that Au@BSA microsphere was used to connect with luminol to enhance its ECL intensity, and it can generate ECL signals at positive potential. Zeolitic Imidazolate Framework-8 (ZIF-8) and Meso-tetra (4-carboxyphenyl) porphyrin (TCPP) were linked using a one-pot method to synthesize a novel luminescent ZIF (L-ZIF) named TZZ, which can emit ECL signals at negative potential. Moreover, magnetite microspheres were used to construct a sandwich-type biosensor to obtain higher sensitivity and reduce background signals. In addition, the biosensor manufactured directly in solution have a wider linear range than constructed on electrode because it has more available space than the electrode surface. Due to the above advantages, the prepared ECL biosensor exhibited high sensitivity, stability and broader linear range, even for practical analysis. Therefore, the prepared ECL biosensor will become a promising method for determination of α2,3-sialylated glycans and α2,6-sialylated glycans in clinical applications in the future. What is more, it provides a potential method for detection of other multi-targets.

Novel Ce(III)-Metal Organic Framework with a Luminescent Property To Fabricate an Electrochemiluminescence Immunosensor.

We designed a novel luminescent metal-organic framework (MOF) named Ce-TCPP-LMOF (CTM) through a simple one-pot solvothermal method. CTM was synthesized by using the emerging electrochemiluminescent (ECL) material (4,4',4″,4‴-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) as the organic ligand and Ce(III) as the metal node. We found that CTM not only has the remarkable ability to emit light but also has a uniform "sandwich biscuit" shape and suitable nanoscale size, which are promising for further applications. We also applied CTM to construct a novel ECL immunosensor and achieve sensitive detection of the proprotein convertase subtilisin/kexin type 9 (PCSK9), a biomarker related to cardiovascular diseases. To further amplify the ECL signal of CTM, a novel dual-amplified signal strategy was established by inducing a polyamidoamine dendrimer (PAMAM) and gold nanoparticles (AuNPs). Importantly, we first proved that the ECL signal of the CTM/S2O82- system could be enhanced by the PAMAM electric field. As the electron transfer rate was accelerated by the AuNP layer, this ECL signal was further enhanced in AuNP-modified electrodes. The ECL immunosensor showed desirable performance for PCSK9 analysis within a detection range of 50 fg mL-1 to 10 ng mL-1 and a low limit of detection of 19.12 ± 2.69 fg mL-1. Real sample detection suggested that the immunosensor holds great potential for analyzing clinical serum samples.

A novel light-electricity sensing method for PCSK9 detection based on s-PdNFs with multifunctional property.

Amounts of studies show that proprotein convertase subtilisin/kexin type 9 (PCSK9) can increase the low-density lipoprotein cholesterol ((LDL-C), leading to the progression and development of atherosclerosis. Hence, design an effective method to detect serum PCSK9 is meaningful for the prevention, monitor and diagnosis of cardiovascular diseases. Here, we reported a dual-signal method for detecting PCSK9 using a signal label, sulphur-doped palladium nanoflowers (s-PdNFs), inspired by its multifunctional properties of quenching and catalysis, which would simultaneously achieve electrochemiluminescence (ECL) analysis and electrochemical detection. For the ECL analysis, s-PdNFs could effectively quench the ECL intensity of peroxydisulfate/oxygen (S2O82-/O2) system via ECL resonance energy transfer (ECL-RET). Importantly, the donor-acceptor pair (s-PdNFs-S2O82- pair) was firstly reported in the ECL-RET field. For the electrochemical detection, s-PdNFs with peroxidase-like activity, produce electric signals by catalyzing H2O2. Herein, a novel light-electricity dual signal immunosensor based on s-PdNFs was developed, and with a broad linear range of 5 fg mL-1 to 50 ng mL-1 (ECL channel) and 500 fg mL-1 to 50 ng mL-1 (electrochemical channel). Furthermore, the ECL channel and electrochemical channel can achieve the detection respectively which can meet different testing instruments. The two channels can also be combined to improve the accuracy of the detection. More importantly, the immunosensor realized the detection of PCSK9 in real serum samples demonstrated by good correlations with ELISA method. Our findings can promote the application of multifunctional materials in sensor and biomedicine field and provide a novel strategy for the detection of serum molecular.

A sensitive sandwich-type immunosensor for the detection of MCP-1 based on a rGO-TEPA-Thi-Au nanocomposite and novel RuPdPt trimetallic nanoalloy particles.

A novel electrochemical immunosensor was proposed for the detection of monocyte chemoattractant protein-1 (MCP-1), a biomarker of cardiovascular disease. Due to thionine (Thi) possessing electroactive redox properties, a one-step approach was utilized to synthesize a reduced graphene oxide-tetraethylene-thionine-Au (rGO-TEPA-Thi-Au) nanocomposite at room temperature using the synergistic effect of Thi and rGO-TEPA towards HAuCl4. We obtained the excellent matrix material, which immobilized more primary antibody MCP-1-Ab1 on rGO-TEPA on a modified glassy carbon electrode (GCE). To further enhance the sensitivity of the sensor, a novel signal generation and amplification strategy was developed for detection. RuPdPt trimetallic nanoalloy particles (RuPdPt TNPs), a novel nanomaterial, were synthesized by a one-pot method, displayed a uniform morphology as well as good electrochemical activity and bound with the secondary antibodies against MCP-1 via the Pt-NH2 bond. Most importantly, RuPdPt TNPs have a significant ability to catalyze H2O2 to produce an electron. The electrochemical signal was highly amplified because the electrochemical signal was primarily derived from the synergistic catalysis of H2O2 by RuPdPt TNPs and recorded by chronoamperometry. Under the optimal conditions, this newly designed biosensor exhibited sensitive detection of MCP-1 in the range from 20 fg mL-1 to 1000 pg mL-1, with a detection limit of 8.9 fg mL-1 (based on a S/N = 3). Additionally, the designed immunosensor showed acceptable selectivity, reproducibility and stability. This immunosensor is a promising strategy for analyzing clinical serum samples in the future.

Trimetallic signal amplification aptasensor for TSP-1 detection based on Ce-MOF@Au and AuPtRu nanocomposites.

In this work, an aptamer was used as the target capturing agent and a trimetallic signal amplification strategy based on Ce-MOF@Au and AuPtRu NPs was demonstrated for the sensitive detection of TSP-1. Herein, the synthesized AuPtRu nanocomposite (AuPtRu NPs) not only acts as the catalyst for catalyzing hydrogen peroxide but also acts as a nanocarrier for capturing the -NH2 termination single strand DNA (S1) to obtain the signal probe (SP, AuPtRu nanocomposite/S1). Then, SP was efficiently linked into TSP-1 aptamers with the addition of complementary linking strands to form M1 (SP/aptamer). The Ce-MOF@Au nanocomposites were obtained by in situ reduction and used as GCE electrode modification materials. The -NH2-modified capture probe (CP) DNA was immobilized on the surface of Ce-MOF@Au nanocomposites for hybridizing SP. In the presence of the target TSP-1, the aptamer recognizes the target and binds strongly so that SP is released from the prepared M1 and then hybridized with CP. When the detection solution contains an electrochemical matrix of H2O2, AuPtRu NPs can oxidize H2O2 to obtain an enhanced signal. Furthermore, the proposed aptasensor has a very low LOD of 0.13 fg mL-1 TSP-1 in the detection range of 1 fg mL-1 to 10 ng mL-1. Moreover, the proposed platform also has application implications for other potential targets.

Dual-type responsive electrochemical biosensor for the detection of α2,6-sialylated glycans based on AuNRs-SA coupled with c-SWCNHs/S-PtNC nanocomposites signal amplification.

In this study, a dual-type responsive electrochemical biosensor was developed for the quantitative detection of α2,6-sialylated glycans (α2,6-sial-Gs), a potential biomarker of tumors. The gold nanorods (AuNRs), which exhibited great specific surface area, as well as good biocompatibility, was synthesized by the way of seed growth method. Furthermore, a biotin-streptavidin (biotin-SA) system was introduced to improve the immunoreaction efficiency. Accordingly, a label-free biosensor was fabricated based on AuNRs-SA for the quick detection of α2,6-sial-Gs by recording the signal of differential pulse voltammetry (DPV). Furthermore, to expand the ultrasensitive detection of α2,6-sial-Gs, a carboxylated single-walled carbon nanohorns/sulfur-doped platinum nanocluster (c-SWCNHs/S-PtNC) was synthesized for the first time as a novel signal label, which showed an excellent catalytic performance. The usage of c-SWCNHs/S-PtNC could significantly amplify the electrochemical signal recorded by the amperometric i-t curve. Herein, a sandwich type biosensor was constructed by combining the AuNRs-SA on the electrode and c-SWCNHs/S-PtNC (signal amplifier). The label-free biosensor possessed a linear range from 5 ng mL-1 to 5 µg mL-1 with a detection limit of 0.50 ng mL-1, and the sandwich-type biosensor possessed a wide linear range from 1 fg mL-1 to 100 ng mL-1 with a detection limit of 0.69 fg mL-1. Furthermore, the biosensor exhibited excellent recovery and stability, indicating its potential for use in actual samples.