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1.
Heliyon ; 10(7): e27768, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38690000

ABSTRACT

Background: Primary tumor resection is associated with survival benefits in patients with metastatic lung adenocarcinoma (mLUAD). However, there are no established methods to determine which individuals would benefit from surgery. Therefore, we developed a model to predict the patients who are likely to benefit from surgery in terms of survival. Methods: Data on patients with mLUAD were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Depending on whether surgery was performed on the primary tumor, patients were categorized into two groups: cancer-directed surgery (CDS) and no-cancer-directed surgery (No-CDS). Propensity Score Matching (PSM) was utilized to address bias between the CDS and No-CDS groups. The prognostic impact of CDS was assessed using Kaplan-Meier analysis and Cox proportional hazard models. Subsequently, we constructed a nomogram to predict the potential for surgical benefits based on multivariable logistic regression analysis using preoperative factors. Results: A total of 89,039 eligible patients were identified, including 6.4% (5705) who underwent surgery. Following PSM, the CDS group demonstrated a significantly longer median overall survival (mOS) compared with the No-CDS group (23 [21-25] vs. 7 [7-8] months; P < 0.001). The nomogram showed robust performance in both the training and validation sets (area under the curve [AUC]: 0.698 and 0.717, respectively), and the calibration curves exhibited high consistency. The nomogram proved clinically valuable according to decision curve analysis (DCA). According to this nomogram, surgical patients were categorized into two groups: no-benefit candidates and benefit candidates groups. Compared with the no-benefit candidate group, the benefit candidate group was associated with longer survival (mOS: 25 vs. 6 months, P < 0.001). Furthermore, no difference in survival was observed between the no-benefit candidates and the no-surgery groups (mOS: 6 vs. 7 months, P = 0.9). Conclusions: A practical nomogram was developed to identify optimal CDS candidates among patients with mLUAD.

2.
Polymers (Basel) ; 15(24)2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38139907

ABSTRACT

The polymer/substrate interface plays a significant role in the dynamics of nanoconfined polymers because of its suppression on polymer mobility and its long-range propagation feature, while the molecular origin of the long-range substrate effect in unentangled polymer material is still ambiguous. Herein, we investigated the propagation distances of the substrate effect (h*) by a fluorinated tracer-labeled method of two unentangled polymer films supported on silicon substrates: linear and ring poly(methyl methacrylate) films with relatively low molecular weights. The results indicate that the value of h* has a molecular weight dependence of h*∝N (N is the degree of polymerization) in the unentangled polymer films, while h*∝N1/2 was presented as previously reported in the entangled films. A theoretical model, depending on the polymer/polymer intermolecular interaction, was proposed to describe the above long-range propagation behavior of the substrate effect and agrees with our experiment results very well. From the model, it revealed that the intermolecular friction determines the long-range propagation of the substrate effect in the unentangled system, but the intermolecular entanglement is the dominant role in entangled system. These results give us a deeper understanding of the long-range substrate effect.

3.
Arch Biochem Biophys ; 748: 109784, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37816420

ABSTRACT

Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.


Subject(s)
Bone Neoplasms , Exosomes , Extracellular Vesicles , Prostatic Neoplasms , Male , Humans , Exosomes/metabolism , Prostatic Neoplasms/pathology , Bone Neoplasms/pathology , Cell Communication , Extracellular Vesicles/metabolism , Tumor Microenvironment , Neoplasm Metastasis
4.
Appl Opt ; 62(19): 5064-5068, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37707207

ABSTRACT

Perovskite has emerged as an outstanding light-absorbing material, leading to significant advancements in solar cell efficiency. Further improvements can be made by restructuring the internal optical properties of perovskite. In this study, we investigate the impact of gold triangle nanostructures on perovskite absorption rates, and we explore the optimization of surface plasmon resonance to enhance its solar absorption efficiency. Our numerical simulations revealed that stacking gold triangle nanostructures in the perovskite film resulted in a significant increase in its absorption rate. Finally, comparative testing showed that the solar spectral absorption rate of a 200 nm thick perovskite film increased by 41.5%.

5.
Am J Pathol ; 193(9): 1248-1266, 2023 09.
Article in English | MEDLINE | ID: mdl-37301536

ABSTRACT

Prostate cancer (PC) is a malignancy with high morbidity and mortality. Bone metastasis is the main driver of short survival time and difficulties in the treatment and prevention of PC. The goal of this study was to explore the biological function of E3 ubiquitin ligase F-box only protein 22 (FBXO22) in PC metastasis and its specific regulation mechanism. According to transcriptome sequencing, FBXO22 was overexpressed in PC tissues (versus adjacent tissues) and bone tissues (versus biopsied bone tissues without bone metastases). Fbxo22 down-regulation reduced bone metastases and macrophage M2 polarization in mice. FBXO22 was down-regulated in macrophages, and polarization was observed by flow cytometry. Macrophages were co-cultured with PC cells and osteoblasts to assess PC cell and osteoblast activity. FBXO22 knockdown restored osteoblast capacity. FBXO22 ubiquitinated and degraded Krüppel-like factor 4 (KLF4), which regulated the nerve growth factor (NGF)/tropomyosin receptor kinase A pathway by repressing NGF transcription. Silencing of KLF4 mitigated the metastasis-suppressing properties of FBXO22 knockdown, whereas NGF reversed the metastasis-suppressing properties of KLF4 in vitro and in vivo. Cumulatively, these data indicate that FBXO22 promotes PC cell activity and osteogenic lesions by stimulating macrophage M2 polarization. It also degrades KLF4 in macrophages and promotes NGF transcription, thereby activating the NGF/tropomyosin receptor kinase A pathway.


Subject(s)
Bone Neoplasms , F-Box Proteins , Prostatic Neoplasms , Humans , Male , Mice , Animals , Nerve Growth Factor/metabolism , Tropomyosin/metabolism , F-Box Proteins/genetics , F-Box Proteins/metabolism , Prostatic Neoplasms/genetics , Signal Transduction , Receptors, Cytoplasmic and Nuclear
6.
Opt Express ; 31(9): 14454-14463, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37157309

ABSTRACT

Twisted light carrying orbital angular momentum (OAM), which features a helical phase front, has shown its potential applications in diverse areas, especially in free-space optical (FSO) communications. Multiple orthogonal OAM beams can be utilized to enable high-capacity FSO communication systems. However, for practical OAM-based FSO communication links, atmospheric turbulence will cause serious power fluctuations and inter-model crosstalk between the multiplexed OAM channels, impairing link performance. In this paper, we propose and experimentally demonstrate a novel OAM mode-group multiplexing (OAM-MGM) scheme with transmitter mode diversity to increase system reliability under turbulence. Without adding extra system complexity, an FSO system transmitting two OAM groups with a total of 144 Gbit/s discrete multi-tone (DMT) signal is demonstrated under turbulence strength D/r0 of 1, 2, and 4. In our experiments, the proposed OAM-MGM scheme helps to achieve bit-error-rate (BER) mostly less than 3.8 × 10-3 under turbulence strength D/r0 of 1 and 2 with a total transmitted power of 10 dBm. Compared with the conventional OAM mode multiplexed system, the system interruption probability decreases from 28% to 4% under moderate turbulence strength D/r0 of 2.

7.
Opt Express ; 31(2): 976-985, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36785144

ABSTRACT

Vortex beam carrying orbital angular momentum (OAM), which features a helical phase front, has shown its potential applications in diverse areas, especially in free-space optical (FSO) communications. However, when generating vortex beams, the radial phase distribution is usually disregarded in previous reports. In this paper, by controlling the radial phase distribution, we propose a method for the generation of vortex beams with arbitrary convex trajectories. By using this method, we successfully generate vortex beams with different predesigned trajectories with high accuracy. Moreover, we also demonstrate the transmission of the radial phase-controlled vortex beams in FSO links for different scenarios in simulation. Firstly, we generate vortex beams with different OAM states (l=+1, + 3, and +6), which have the same ring diameter at the receiver side. Secondly, we generate three vortex beams (l=+3) with the same ring diameter at different transmission distances (z = 100 m, 200 m, and 300 m). Finally, by carefully controlling the radial phase of the vortex beam, we generate vortex beams that can almost keep the same ring diameter for a long distance. The proposed method for shaping the transmission trajectory of vortex beams may pave the way for more applications in OAM-based FSO communications.

8.
J Orthop Surg Res ; 17(1): 572, 2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36578051

ABSTRACT

PURPOSE: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a secreted protein associated with inflammation, is believed to possess momentous and multiple anti-inflammatory and tissue-protective properties. However, the role and potential mechanism of TSG-6 in cervical disk degeneration (CDD) are still not clear. Hence, we aimed to explore the effect of TSG-6 on CDD. METHODS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or enzyme-linked immunosorbent assay was applied to detect the expression level of TSG-6 and IL-1ß in normal and degenerated nucleus pulposus (NP) tissues. Then, qRT-PCR and western blot were adopted to test the TSG-6 protein expression after IL-1ß treatment (10 ng/mL) in human NP cells (HNPCs). After over-expressing TSG-6, qRT-PCR was also utilized to evaluate the expression of TNF-α, IL-8, and IL-6 and the synthesis of sulfated glycosaminoglycans (sGAGs), western blot to check the expression of extracellular matrix (ECM) proteins [collagen II, aggrecan, and matrix metalloproteinase-3 (MMP-3)], pain-related molecules (CGRP, calcitonin gene-related peptide; NGF, nerve growth factor; SP, substance P), and PI3K/Akt signaling pathway-related proteins. RESULTS: Briefly speaking, TSG-6 and IL-1ß expression levels were significantly increased in CDD patient tissues; and IL-1ß treatment could significantly increase TSG-6 expression in HNPCs. Further research revealed that, in addition to greatly promoting sGAGs synthesis, TSG-6 over-expression also inhibited TNF-α, IL-8, and IL-6 expression and ECM degradation in IL-1ß-induced HNPCs. (The collagen II and aggrecan expression was up-regulated and MMP-3 expression was down-regulated.) Furthermore, over-expression of TSG-6 could decrease the levels of CGRP, NGF, and SP protein expression and activate the PI3K/Akt signaling pathway in IL-1ß-treated HNPCs. CONCLUSION: TSG-6 inhibits inflammatory responses, ECM degradation, and expression of pain-related molecules in IL-1ß-induced HNPCs by activating the PI3K/Akt signaling pathway.


Subject(s)
Intervertebral Disc Degeneration , Nucleus Pulposus , Humans , Proto-Oncogene Proteins c-akt/metabolism , Nucleus Pulposus/metabolism , Tumor Necrosis Factor-alpha/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Matrix Metalloproteinase 3/metabolism , Nerve Growth Factor/pharmacology , Aggrecans/metabolism , Interleukin-6/metabolism , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/pharmacology , Interleukin-8/metabolism , Interleukin-8/pharmacology , Signal Transduction , Intervertebral Disc Degeneration/pathology , Extracellular Matrix Proteins/metabolism , Extracellular Matrix/metabolism , Cells, Cultured , Interleukin-1beta/pharmacology , Interleukin-1beta/metabolism
9.
Aging (Albany NY) ; 14(24): 10050-10066, 2022 12 23.
Article in English | MEDLINE | ID: mdl-36566018

ABSTRACT

Prostate cancer is the most prevalent genitourinary malignant cancer in men worldwide. Patients with prostate cancer who progress to castration-resistant prostate cancer (CRPC) or metastatic CRPC have significantly poorer survival. Advanced prostate cancer is a clinical challenge due to the lack of effective treatment strategies. In the field of oncology, SGOL2 was an emerging and differentially expressed molecule, which enhanced the proliferation of cell populations in vitro in our studies. Mass spectrum and Co-IP validated the interaction of SGOL2 and RAB1A in a protein-protein manner. We further investigated the role of SGOL2 in the regulatory mechanism of RAB1A in prostate cancer cell lines. Furthermore, SGOL2 regulated RAB1A expression by inhibiting its ubiquitination. Rescue Experiments demonstrated that SGOL2 promoted prostate cancer cell proliferation and migration by upregulating RAB1A expression. Finally, we found that SGOL2 and RAB1A may regulate the tumor microenvironment (TME) in prostate cancer. In conclusion, our findings concluded that SGOL2 stabilized RAB1A expression to promote prostate cancer development. Both of them were of great importance in TME modulation.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/metabolism , Treatment Outcome , Ubiquitination , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Tumor Microenvironment
10.
Cancer Drug Resist ; 5(1): 15-24, 2022.
Article in English | MEDLINE | ID: mdl-35582532

ABSTRACT

Aim: The objective of our study was to assess the efficacy of immune checkpoint inhibitors (ICIs) on patients with non-small-cell lung cancer (NSCLC) harboring oncogenic alterations. Methods: We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy. Major characteristics including PD-L1 expression, treatment, and survival were analyzed. Results: In total, 309 non-squamous NSCLC patients with a median age of 61 years (range 20-88 years) including 70.9% male were retrospectively enrolled. The molecular alterations involved epidermal growth factor receptor (EGFR) (n = 81), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (n = 31), anaplastic lymphoma kinase (ALK) (n = 1), human epidermal growth factor receptor 2 (HER2) (n = 12), V-raf murine sarcoma viral oncogene homolog (BRAF) (n = 2), rearranged during transfection (n = 4), and c-ros oncogene 1 (ROS1) (n = 3). In the EGFR subset, the ORR was 30.9% (n = 81) and PFS was significantly shorter than WT group (median PFS: 5.7 months vs. 7.1 months; P = 0.0061). In subgroup analyses, ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy (median PFS: 7.7 months vs. 4.7 months; P = 0.0112). In KRAS patients, ORR was 51.6% (n = 31). No significant difference was found in subgroup analyses. The ORR and PFS were 16.7% (n = 12) and 28.6% (n = 7), 7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients, respectively. Three ROS1 patients were enrolled with a PFS of 16.0, 34.2, and 45.0 months individually, and one ALK patient with PFS of 4.4 months was identified. No response was found in two BRAF patients. Conclusion: ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC. ICI-based combination therapy could be considered for patients with ROS1 rearrangement, HER2 mutation and EGFR Exon20 insertion NSCLC.

11.
Opt Express ; 29(20): 32580-32590, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34615324

ABSTRACT

Vortex beams carrying orbital angular momentum (OAM), which feature helical wavefronts, have been regarded as an alternative degree of freedom for free-space optical (FSO) communication systems. However, in practical applications, atmospheric turbulence and limited-size receiving aperture effects will cause OAM modal degradation and seriously reduce the received power. In this paper, by controlling the radial phase distribution of conventional OAM beams, quasi-ring Airy vortex beams (QRAVBs) are successfully generated in the experiments to increase the received power under the limited-size receiving aperture conditions. By employing 72-Gbit/s 16-ary quadrature amplitude modulation (16-QAM) discrete multi-tone (DMT) signals, we successfully demonstrate free-space data transmission with QRAVBs in the experiments. Moreover, the transmission performance of QRAVBs under atmospheric turbulence is also evaluated. Comparing with conventional OAM beam and Bessel beam, the obtained results show that QRAVBs can achieve higher received power and better BER performance under limited-size receiving aperture and atmospheric turbulence conditions.

12.
ACS Sens ; 6(10): 3564-3574, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34606243

ABSTRACT

Digital polymerase chain reaction (dPCR) has found widespread applications in molecular diagnosis of various diseases owing to its sensitive single-molecule detection capability. However, the existing dPCR platforms rely on the auxiliary procedure to disperse DNA samples, which needs complicated operation, expensive apparatus, and consumables. Besides, the complex and costly dPCR readers also impede the applications of dPCR for point-of-care testing (POCT). Herein, we developed a portable digital loop-mediated isothermal amplification (dLAMP) platform, integrating a microscale hydrogel (microgel) array chip for sample partition, a miniaturized heater for DNA amplification, and a hand-held reader for digital readout. In the platform, the chip with thousands of isolated microgels holds the capability of self-absorption and partition of DNA samples, thus avoiding auxiliary equipment and professional personnel operations. Using the integrated dLAMP platform, λDNA templates have been quantified with a good linear detection range of 2-1000 copies/µL and a detection limit of 1 copy/µL. As a demonstration, the epidermal growth factor receptor L858R gene mutation, a crucial factor for the susceptibility of the tyrosine kinase inhibitor in non-small-cell lung cancer treatment, has been accurately identified by the dLAMP platform with a spiked plasma sample. This work shows that the developed dLAMP platform provides a low-cost, facile, and user-friendly solution for the absolute quantification of DNA, showing great potential for the POCT of nucleic acids.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Microgels , Humans , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques
13.
Clin Cancer Res ; 27(22): 6184-6196, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34446541

ABSTRACT

PURPOSE: Having emerged as a noninvasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of circulating tumor DNA (ctDNA) of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation. EXPERIMENTAL DESIGN: Primary cohort encompasses 5,671 blood samples from 4,892 patients with lung cancer. Pair-wise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue tumor mutational burden (TMB). Parallel sequencing with plasma/tissue and white blood cells was performed using a 1,021-gene panel. RESULTS: Histologic subtyping was the most relevant to ctDNA detectability independent of other demographic characteristics, with small cell lung cancer showing the highest detectability, ctDNA abundance, and blood TMB (bTMB). Mutational landscape demonstrated significant differences, and integrated clonality analysis highlighted distinct driver-pattern and functional pathway interaction among various subtypes. The clonality and concurrent genes of EGFR mutations could predict the therapeutic efficacy of tyrosine kinase inhibitors (TKI), and RB1 mutations in non-small cell lung cancer characterized a subset with high bTMB, elevated ctDNA level, and potential small cell transformation. Most importantly, we developed an adjusted algorithm for bTMB in samples with extremely low ctDNA level and validated its correlation with tissue TMB in an independent cohort. CONCLUSIONS: ctDNA could serve as a promising alternative in genomic profiling for lung cancer. The novel identification of ctDNA clonality and adjusted bTMB might improve therapeutic and prognostic evaluation. This dataset was also a valuable resource for the development of new therapeutic targets and new genomically guided clinical trials.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , Lung Neoplasms , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/drug therapy , China , Circulating Tumor DNA/genetics , Humans , Lung Neoplasms/drug therapy , Mutation
14.
Sci Rep ; 11(1): 12012, 2021 Jun 08.
Article in English | MEDLINE | ID: mdl-34103592

ABSTRACT

Vortex beams carrying orbital angular momentum (OAM), which featuring helical phase front, have been regarded as an alternative spatial degree of freedom for optical mode coding and multiplexing. For most reported OAM-based mode coding schemes, data information is only encoded by different OAM mode states. In this paper, we introduce a novel design technique to construct vortex array phase grating (VAPGs) for the flexible generation of vortex arrays, and employ the proposed VAPGs to realize multi-dimensional space/mode/amplitude coding/decoding. By designing VAPGs with different parameters and loading them on to a single spatial light modulator (SLM), we successfully generate vortex array with different mode states and relative power in the experiments. Moreover, a 10-bit multi-dimensional space/mode/amplitude data coding/decoding scheme for image transfer in free-space link with a zero bit-error-rate is experimentally demonstrated, which confirm the feasibility of our proposed VAPG-based coding/decoding scheme.

15.
Opt Express ; 29(9): 13171-13182, 2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33985057

ABSTRACT

Twisted light carrying orbital angular momentum (OAM), which features helical phase front, has shown its potential applications in diverse areas, especially in optical communications. For OAM-based free-space optical (FSO) links, a significant challenge is the power fading induced by atmospheric turbulence. In this paper, we experimentally demonstrate the mitigation of atmospheric turbulence effects with an OAM-based transmitter mode diversity scheme. By designing multi-OAM phase patterns, we successfully generate multiple OAM modes (OAM-1,0,1, OAM+2,+3,+4, OAM+5,+6,+7) carrying the same data stream for transmitter diversity without adding system complexity. An intensity-modulated direct-detection (IM-DD) system with 39.06 Gbit/s discrete multi-tone (DMT) signal is employed to confirm the feasibility of the OAM-based transmitter mode diversity scheme under atmosphere turbulence. The obtained experimental results show that the received power fluctuation and average bit-error rate (BER) are decreased under moderate to strong turbulence compared to the traditional single OAM mode transmission. In addition, the required transmitted power at 10% interruption probability is relaxed by nearly 2 dB under moderate to strong turbulence.

16.
Ann Transl Med ; 9(8): 705, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33987403

ABSTRACT

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive and proliferative disease, with little progress being having made for its treatment in decades. Our goal was to evaluate the effect of immune checkpoint inhibitors (ICIs) and identify optimal first-line interventions for the treatment of SCLC. METHODS: A systematic literature search of the Cochrane Library, PubMed and oncology conference proceedings were conducted. Randomized trials evaluating ICIs for SCLC were included. We use the risk of bias tool in RevMan 5.3 to assess the quality of studies. We used Stata version 15.0 to carry out data direct comparison and R version 4.0.2 to conduct the Bayesian network analysis. RESULTS: A total of 16 relevant clinical trials comprising 4,476 patients were included. We found the magnitude of efficacy for ICIs as first-line therapy conferred a statistically significant benefit in overall survival (OS) and progression-free survival compared to chemotherapy alone. The results were 0.82 (95% CI, 0.76-0.89, P<0.001) and 0.80 (95% CI, 0.74-0.86, P<0.001). For objective response rate (ORR), the result (1.13, 95% CI, 0.97-1.31, P=0.109) was not significant. In the second-line and maintenance treatment, no additional benefit was observed. With regard to safety, results showed that for all grades of AEs and grades 3-4 AEs, the pooled results were 1.36 (95% CI: 0.50-3.70; P=0.543) and 1.35 (95% CI: 0.58-3.15; P=0.484) respectively. In addition, the indirect comparison results showed that nivolumab combined with chemotherapy led to the most significant improvement in OS, while durvalumab combined with chemotherapy was a more efficacious therapy for improving ORR compared with the other interventions; the probability were the best treatments was 73.93% and 81% respectively. DISCUSSION: Our results showed ICIs combined with etoposide and platinum-based drugs as first-line treatment of SCLC have benefits for patients and there was no evidence of a significant difference in efficacy among the different ICI drugs used for the first-line therapy. As for toxicity, the ICIs did not increase the frequency AEs for patients. However, as some studies are ongoing and the full data have still not been reported, our conclusions may not be completely representative.

17.
Oncol Lett ; 21(1): 6, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33240412

ABSTRACT

Human esophageal cancer (hESC) cell motility adopts various modes, resulting in hESC progression and poor survival. However, how tripartite motif 59 (TRIM59), as the ubiquitination machinery, participates in hESC metastasis is not completely understood. The results indicated that TRIM59 was aberrantly upregulated in hESC tissues compared with adjacent healthy esophageal tissues, which was associated with poor survival and advanced TNM state among patients with hESC. Moreover, patients with hESC with higher TRIM59 expression displayed undetectable p53 expression, which contributed to enhanced progression and motility of hESC. At the molecular level, TRIM59 was indicated to be an E3 putative ubiquitin ligase that targeted the p53 protein, leading to increased degradation of p53, which resulted in decreased chemosensitivity to cisplatin. TRIM59 knockdown reduced TRIM59 expression, increased p53 protein expression, and decreased hESC cell viability, clone formation and migration compared with the small interfering RNA negative control (siNC) group. Furthermore, hESC cell lines were more sensitive to cisplatin in the TRIM59-knockdown group compared with the siNC group. The results indicated a relationship between TRIM59, p53 and the chemosensitivity of cisplatin. The present study suggested that TRIM59 may serve as a promising prognostic indicator for patients with hESC.

18.
Anal Chem ; 92(7): 4771-4779, 2020 04 07.
Article in English | MEDLINE | ID: mdl-32157867

ABSTRACT

Mechanical microenvironment plays a key role in the regulation of the phenotype and function of cardiac cells, which are strongly associated with the intracellular redox mechanism of cardiomyocytes. However, the relationship between the redox state of cardiomyocytes and their mechanical microenvironment remains elusive. In this work, we used polyacrylamide (PA) gels with varying stiffness (6.5-92.5 kPa) as the substrate to construct a mechanical microenvironment for cardiomyocytes. Then we employed scanning electrochemical microscopy (SECM) to in situ characterize the redox state of a single cardiomyocyte in terms of the apparent rate constant (kf) of the regeneration rate of ferrocenecarboxylic by glutathione (GSH) released from cardiomyocyte, which is the most abundant reactant of intracellular reductive-oxidative metabolic cycles in cells and can represent the redox level of cardiomyocytes. The obtained SECM results show that the cardiomyocytes cultured on the stiffer substrates present lower kf values than those on the softer ones, that is, the more oxidative state of cardiomyocytes on the stiffer substrates compared to those on the softer ones. It proves the relationship between mechanical factors and the redox state of cardiomyocytes. This work can contribute to understanding the intracellular chemical process of cardiomyocytes during physiopathologic conditions. Besides, it also provides a new SECM method to in situ investigate the redox mechanism of cardiomyocytes at a single-cell level.


Subject(s)
Acrylic Resins/chemistry , Myocytes, Cardiac/metabolism , Single-Cell Analysis , Acrylic Resins/chemical synthesis , Animals , Cells, Cultured , Gels/chemical synthesis , Gels/chemistry , Glutathione/chemistry , Glutathione/metabolism , Microscopy, Electrochemical, Scanning , Myocytes, Cardiac/cytology , Oxidation-Reduction , Rats , Software
19.
Int J Med Microbiol ; 309(3-4): 225-231, 2019.
Article in English | MEDLINE | ID: mdl-31054808

ABSTRACT

Brucella species are the causative agents of brucellosis, a worldwide zoonotic disease that affects a broad range of mammals and causes great economic losses. Small regulatory RNAs (sRNAs) are post-transcriptional regulatory molecules that participate in the stress adaptation and pathogenesis of Brucella. In this study, we characterized the role of a novel sRNA, BSR1141, in the intracellular survival and virulence of Brucella melitensis. The results show that BSR1141 was highly induced during host infections and under in vitro stress situations that simulated the conditions encountered within host phagocytes. In addition, a BSR1141 mutant showed reduced survival both under in vitro stress conditions and in mice, confirming the role of BSR1141 in Brucella intracellular survival. Bioinformatic and experimental approaches revealed that BSR1141 affects the expression of many target genes, including the Brucella virulence component virB2. These data indicate that BSR1141 could influence the expression of virB2, which is important for B. melitensis pathogenesis and intracellular survival. This work provides new insight into the mechanism of adaptation to environmental stress and into the pathogenesis of intracellular pathogens.


Subject(s)
Brucella melitensis/physiology , Brucella melitensis/pathogenicity , RNA, Small Untranslated/metabolism , Virulence Factors/genetics , Animals , Brucella melitensis/genetics , Brucellosis/microbiology , Female , Gene Expression Regulation, Bacterial , Macrophages/metabolism , Macrophages/microbiology , Mice, Inbred BALB C , Microbial Viability , Mutation , RNA, Bacterial/genetics , RNA, Bacterial/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Untranslated/genetics , Spleen/microbiology , Stress, Physiological , Virulence/genetics
20.
PLoS One ; 11(9): e0162657, 2016.
Article in English | MEDLINE | ID: mdl-27631789

ABSTRACT

Independent component analysis (ICA) as a promising spatial filtering method can separate motor-related independent components (MRICs) from the multichannel electroencephalogram (EEG) signals. However, the unpredictable burst interferences may significantly degrade the performance of ICA-based brain-computer interface (BCI) system. In this study, we proposed a new algorithm frame to address this issue by combining the single-trial-based ICA filter with zero-training classifier. We developed a two-round data selection method to identify automatically the badly corrupted EEG trials in the training set. The "high quality" training trials were utilized to optimize the ICA filter. In addition, we proposed an accuracy-matrix method to locate the artifact data segments within a single trial and investigated which types of artifacts can influence the performance of the ICA-based MIBCIs. Twenty-six EEG datasets of three-class motor imagery were used to validate the proposed methods, and the classification accuracies were compared with that obtained by frequently used common spatial pattern (CSP) spatial filtering algorithm. The experimental results demonstrated that the proposed optimizing strategy could effectively improve the stability, practicality and classification performance of ICA-based MIBCI. The study revealed that rational use of ICA method may be crucial in building a practical ICA-based MIBCI system.


Subject(s)
Automation , Brain-Computer Interfaces , Imagery, Psychotherapy , Algorithms , Electroencephalography , Humans
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