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"Jin, Qi"
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الأجراس الذهبية
في قرية فاولا وتشوانغ أراد السيد قاو العثور على زوج لابنته الصغرى ولكن الأمر انتهى به الشيطان الخنزير ودعا السيد قاو الكثيرين لإخضاع الشيطان لكنهم فشلوا. وعندما سمع سان تسائخ والقرد أثناء رحلتهما إلى الغرب أن هناك شيطانا في القرية، تطوع الفرد للمساعدة، والتقى بالشيطان الخنزير وحاربه ولحق به إلى كيفه. أدرك الشيطان الخنزير أن سان تسانغ والقرد في رحلة لإحضار الكتب المقدسة، فأخبر القرد أنه كان ينتظرهما بعدما تلقى تعليمات من قوان بن. لكن القرد لم يصدقه فطلب منه أن يحرق كهفه ثم سيأخذه لمقابلة سان تسانغ فك سان تسانغ وثاق الشيطان الخنزير واتخذه تلميذا ثانيا له. واتضح أن الشيطان الخنزير كان قائدا في السماء ولكنه نفي إلى العالم الأرضي لسوء سلوكه، ومنحته قوان بن اسم وو ننغ ثم منحه سان تسانغ اسم \"با جیه\".
Book
Optimized transmission of multi-path low-latency routing for electricity internet of things based on SDN task distribution
With the continuous development of 5G network, how to further improve the routing and transmission efficiency of electric power IoT has become a popular research at present. Facing the current problems of high data transmission delay, low efficiency, and large task volume in the electric power IoT, this research combines software-defined networking to design a multi-path low-latency routing and transmission model under the concept of task allocation. First, the grid data communication network model and network slicing technology in 5G power IoT are introduced. On this basis, considering the data transmission in the core network in the power IoT, a multi-path low-latency routing optimization transmission model based on software-defined network task allocation is designed by combining the software-defined network controller and task allocation concept. The results indicated that the average delay of the designed model is only 15.78ms when the transmission task size is 10KB and 23.38ms when the transmission task size is 50KB. In addition, the designed model was able to achieve a throughput of 298bps in the local area network and the lowest jitter and packet loss in the wide area network, which are 0.13ms and 0.001%. It can be concluded that the constructed multi-path low-latency routing and transmission model can not only provide theoretical guidance for the optimization of data transmission in the power IoT, but also lay the foundation for the in-depth application and development of software-defined networking in the power IoT and other fields.
Journal Article
Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis
To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
Systematic review and network meta-analysis.
Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
PROSPERO CRD42017082553.
Journal Article
Exosomal miR‐21‐5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1
Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumour‐associated microenvironment. However, the role of MSC‐derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not been thoroughly clarified until now. In this study, we established a co‐culture model for human bone marrow‐derived MSCs with osteosarcoma cells, then extraction of exosomes from induced MSCs and study the role of MSC‐derived exosomes in the progression of osteosarcoma cell. The aim of this study was to address potential cell biological effects between MSCs and osteosarcoma cells. The results showed that MSC‐derived exosomes can significantly promote osteosarcoma cells’ proliferation and invasion. We also found that miR‐21‐5p was significantly over‐expressed in MSCs and MSC‐derived exosomes by quantitative real‐time polymerase chain reaction (qRT‐PCR), compared with human foetal osteoblastic cells hFOB1.19. MSC‐derived exosomes transfected with miR‐21‐5p could significantly enhance the proliferation and invasion of osteosarcoma cells in vitro and in vivo. Bioinformatics analysis and dual‐luciferase reporter gene assays validated the targeted relationship between exosomal miR‐21‐5p and PIK3R1; we further demonstrated that miR‐21‐5p‐abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells. In summary, our study provides new insights into the interaction between human bone marrow MSCs and osteosarcoma cells in tumour‐associated microenvironment.
Journal Article
The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors
A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months,
p
= 0.0011; 53.3% vs 13.3%,
p
= 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (
p
= 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (
p
< 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (
p
= 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.
Journal Article
Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking
Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn
2+
) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO
2
group, Zn
2+
can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn
2+
and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO
2
(98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.
Immune response and new tissue formation are important aspects of tissue repair but often only one aspect is considered in biomedical interventions. Here, the authors report on the use of a mussel-like surface coating to immobilize immune modulating metal ions and growth factors and demonstrated improved in vivo outcomes.
Journal Article
Improvement of Pest Resistance in Transgenic Tobacco Plants Expressing dsRNA of an Insect-Associated Gene EcR
The adoption of pest-resistant transgenic plants to reduce yield loss and pesticide utilization has been successful in the past three decades. Recently, transgenic plant expressing double-stranded RNA (dsRNA) targeting pest genes emerges as a promising strategy for improving pest resistance in crops. The steroid hormone, 20-hydroxyecdysone (20E), predominately controls insect molting via its nuclear receptor complex, EcR-USP. Here we report that pest resistance is improved in transgenic tobacco plants expressing dsRNA of EcR from the cotton bollworm, Helicoverpa armigera, a serious lepidopteran pest for a variety of crops. When H. armigera larvae were fed with the whole transgenic tobacco plants expressing EcR dsRNA, resistance to H. armigera was significantly improved in transgenic plants. Meanwhile, when H. armigera larvae were fed with leaves of transgenic tobacco plants expressing EcR dsRNA, its EcR mRNA level was dramatically decreased causing molting defects and larval lethality. In addition, the transgenic tobacco plants expressing H. armigera EcR dsRNA were also resistant to another lepidopteran pest, the beet armyworm, Spodoptera exigua, due to the high similarity in the nucleotide sequences of their EcR genes. This study provides additional evidence that transgenic plant expressing dsRNA targeting insect-associated genes is able to improve pest resistance.
Journal Article
Radiomics of 18F-FDG PET/CT images predicts clinical benefit of advanced NSCLC patients to checkpoint blockade immunotherapy
IntroductionImmunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment 18F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy.MethodsThis study included 194 patients with histologically confirmed stage IIIB-IV NSCLC with pretreatment PET/CT images. Radiomics features were extracted from PET, CT, and PET+CT fusion images based on minimum Kullback–Leibler divergence (KLD) criteria. The radiomics features from 99 retrospective patients were used to train a multiparametric radiomics signature (mpRS) to predict DCB using an improved least absolute shrinkage and selection operator (LASSO) method, which was subsequently validated in both retrospective (N = 47) and prospective test cohorts (N = 48). Using these cohorts, the mpRS was also used to predict progression-free survival (PFS) and overall survival (OS) by training nomogram models using multivariable Cox regression analyses with additional clinical characteristics incorporated.ResultsThe mpRS could predict patients who will receive DCB, with areas under receiver operating characteristic curves (AUCs) of 0.86 (95%CI 0.79–0.94), 0.83 (95%CI 0.71–0.94), and 0.81 (95%CI 0.68–0.92) in the training, retrospective test, and prospective test cohorts, respectively. In the same three cohorts, respectively, nomogram models achieved C-indices of 0.74 (95%CI 0.68–0.80), 0.74 (95%CI 0.66–0.82), and 0.77 (95%CI 0.69–0.84) to predict PFS and C-indices of 0.83 (95%CI 0.77–0.88), 0.83 (95%CI 0.71–0.94), and 0.80 (95%CI 0.69–0.91) to predict OS.ConclusionPET/CT-based signature can be used prior to initiation of immunotherapy to identify NSCLC patients most likely to benefit from immunotherapy. As such, these data may be leveraged to improve more precise and individualized decision support in the treatment of patients with advanced NSCLC.
Journal Article
Non-linear association between AKI alert detection rate by physicians and medical costs
Acute kidney injury (AKI) is associated with high mortality rates and long-term adverse outcomes and significantly increases medical costs. The AKI electronic alert system built the AKI diagnostic algorithm into the medical system, along with automated collection of key indications and generation of alerts. However, the relationship between the AKI electronic alert system and medical costs is still unknown.
An exploratory secondary analysis of data from a double-blinded, multicenter, parallel, randomized controlled trial to investigate the association between the AKI electronic alert system and medical costs.
Finally, a total of 6030 patients were enrolled in this study. Multivariate logistic regression analysis revealed that the alert group was not significantly associated with medical costs (all p-values > 0.05). However, the rate of alert detection by an attending physician demonstrated a notable negative correlation with medical costs; adjusted effects for direct and total costs were -126.78$ and -236.82$, respectively. The curve fitting and threshold effect analysis revealed that when the rate of alert detection by an attending physician was between 18% and 59%, each unit increase in the rate corresponded to decreases in direct cost by 363.94 (-463.34, -264.55) $ and in total cost by 698.93 (-885.78, -512.07) $. Our subgroup analysis also found a significant relationship between the rate and medical costs.
The alert group did not significantly reduce medical costs compared to the usual care group. However, the rate of alert detection by an attending physician had a significant negative association with medical costs, and there was a threshold effect between them. When the rate was between 18% and 59%, medical costs decreased as the rate increased, and when the rate was < 18% or ≥ 59%, medical costs did not decrease as the rate increased.
Journal Article