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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： si-yang liu Song Dong Xue-Ning yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji yang Qing Zhou Hong-Rui Li Ke liu Wendy Wu si-yang Maggie liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

An immunological storm for cancer therapy: 2018 Nobel Prize in Physiology or Medicine

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Science Bulletin 2018年第24期63卷 1608-1610页

作者： si-yang liu Yi-Long Wu Guangdong General Hospital School of MedicineSouth China University of Technology

Immunotherapy with checkpoint inhibitors (CPIs)is a new approach to cancer therapy that harnesses and enhances the innate abilities of the immune system to recognize and fight *** has become a breakthrough in the history of cancer treatment and is of epoch-making significance [1 ]. In the past century,Nobel Prize has been awarded to the advances in immunology for 15 *** year,it won for the 16th *** *** from the University of Texas MD Anderson Cancer Center and Japanese immunologist Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine,for their great contributions to the discovery of the CTLA-4 and PD-1 and the development of promising cancer therapy by inhibition of negative immune *** research shows how different strategies to inhibit the brakes on the immune system can be used in the treatment of cancer,which became a landmark in the history of cancer therapy.

关键词： Immunotherapy checkpoint inhibitors cancer

Over-sampling basis expansion model aided channel estimation for OFDM systems with ICI

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The Journal of China Universities of Posts and Telecommunications 2008年第4期15卷 7-13页

作者： liu si-yang liu Yuan-an WANG Fei-fei XIE Gang ZHANG Ran-ran Key Laboratory of Universal Wireless Communications (Beijing University of Posts and Telecommunications) Ministry of Education Beijing 100876 China

The rapid variation of channel can induce the intercarrier interference in orthogonal frequency-division multiplexing （OFDM） systems. Intercarrier interference will significantly increase the difficulty of OFDM channel estimation because too many channel coefficients need be estimated. In this article, a novel channel estimator is proposed to resolve the above problem. This estimator consists of two parts： the channel parameter estimation unit （CPEU）, which is used to estimate the number of channel taps and the multipath time delays, and the channel coefficient estimation unit （CCEU）, which is used to estimate the channel coefficients by using the estimated channel parameters provided by CPEU. In CCEU, the over-sampling basis expansion model is resorted to solve the problem that a large number of channel coefficients need to be estimated. Finally, simulation results are given to scale the performance of the proposed scheme.

关键词： OFDM ICI over-sampling basis expansion model (OBEM)

Wetting and corrosion behavior between magnesia-carbon refractory and converter slags with different MgO contents

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Journal of Iron and Steel Research International 2022年第7期29卷 1073-1079页

作者： Rui-qiang Bai si-yang liu Fei-xiong Mao Yuan-yuan Zhang Xin yang Zhi-jun He School of Materials and Metallurgy University of Science and Technology LiaoningAnshan 114051LiaoningChina Ningbo Key Laboratory of Marine Protection Materials Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201ZhejiangChina

The influence of MgO content in slag on wetting and corrosion behavior between slag and MgO–C refractory was *** can be known from the high-temperature wetting experiment that as the MgO content in the slag increases,the final contact angle between the slag and the MgO–C refractory gradually increases and the penetration depth of the slag into the refractory gradually decreases from 60.54μm(when the MgO content is 8%)to 28.11μm(when the MgO content is 12%).The CaO and siO_(2)in the slag penetrate into the MgO–C refractory along the pores or surface cracks formed by carbon oxidation and react with MgO to generate a large amount of low-melting compound CaO–MgO–siO_(2),which accelerates the corrosion of the *** the MgO content in slag increases,the viscosity of the slag increases and the fluidity becomes worse,so that the mass transfer and diffusion of molecules or ions in the slag are *** addition,the increase in MgO reduces the activity of FeO in the slag,which inhibits the interfacial chemical reaction,thereby weakening the wetting effect caused by the reaction.

关键词： Converter slag MgO–C refractory MgO content Wetting Corrosion

Expression and effect of TLR4 in rats with diabetic nephropathy

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Asian Pacific Journal of Tropical Medicine 2013年第8期6卷 635-639页

作者： si-yang liu Xiang-Zhi Nie Wen-yang Zhou Jing Chen Department of Orthopaedics Renmin Hospital of Wuhan University Department of Nephrology Wuhan No.1 Hospital

Objective: To observe the expression of TLR4 in kidney tissue of rats with diabetic nephropathy and discuss the role of TLR4 in the occurrence and development of the diabetic nephropathy. Methods: A total of 60 clean male SD rats were selected and randomly divided into the modeling group and control group after 1 week of breeding, including 30 rats in each group. Biochemical indices as well as the protein expression of TLR4 were observed and compared between two groups at 2 w, 4 w, 6 w, 8 w and 12 w after the modeling, and the correlation between TLR4 and each biochemical indexes was analyzed. Results: Rats in the modeling group had higher levels of blood glucose, 24-hour urine protein and blood urea nitrogen after the modeling, and showed the increase in the serum creatinine, kidney/body weight ratio, CRP and serum TNF-毩 at 4w after the modeling, with the significant difference compared to results of the control group ( P significantly higher than those in the control group, with the statistically significant difference ( P sion of TLR4 at each time point in the control group was relatively low. Rats in the modeling group had the high expression of TLR4 in kidney's glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with the significant difference compared to the control group ( P sion in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups ( P sion of TLR4 and the increased serum titer of 24hour urine protein excretion, serum creatinine, CRP and TNF-毩. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a role in the occurrence and development

关键词： Diabetic nephropathy TLR4 Glomerulus

A photo-elutable and template-free isothermal amplification strategy for sensitive fluorescence detection of 5-formylcytosine in genomic DNA

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Chinese Chemical Letters 2023年第3期34卷 166-170页

作者： Hongling yang Yanfei Zhang Zhenning Yu si-yang liu Yuzhi Xu Zong Dai Xiaoyong Zou School of Chemistry Sun Yat-sen UniversityGuangzhou 510275China Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument School of Biomedical EngineeringSun Yat-sen UniversityShenzhen 518107China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China

5-Formylcytosine(5fC), as an important epigenetic modification, plays a vital role in diverse biological processes and multiple diseases by regulating gene expression. Owing to the extremely low abundance of 5fC in all mammalian tissues and high structural similarity with other cytosine derivatives, the precise and sensitive detection of 5fC is challenging. Herein, a photo-elutable and template-free isothermal amplification strategy has been proposed for the sensitive detection of 5fC in genomic DNA based on5fC-specific biotinylation, enrichment, photocleavage, and terminal deoxynucleotidyl transferase(Td T)-assisted fluorescence signal amplification, which is termed 5fC-PTIAS. By introducing the highly specific chemolabeling and the one-step photoelution processes, this strategy possesses a minimal nonspecific background as well as a much higher amplification efficiency. With the high signal-to-noise ratio, this strategy can achieve the accurate quantification of 5fC in various biological samples including mouse brain, kidney, and liver, with a limit of detection(LOD) of 0.025‰ in DNA(S/N=3). These results not only confirm the widespread distribution of 5fC but also indicate its significant variation in different tissues and ages. The bisulfite-and mass spectrometry-free strategy is highly sensitive, selective, and easily mastered, holding great promise in detecting other epigenetic modifications with much lower levels.

关键词： 5-Formylcytosine DNA demethylation Fluorescence detection Isothermal amplification Magnetic separation

PD-L1表达指导的信迪利单抗与帕博利珠单抗联合或不联合含铂双药化疗治疗未经治晚期非小细胞肺癌患者:一项2期随机对照试验(CTONG1901)

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Science Bulletin 2024年第4期69卷 535-543页

作者：刘思阳黄婕邓嘉怡徐崇锐严红虹杨明意黎扬斯柯娥娥郑明英王震林嘉欣甘彬张绪超陈华军汪斌超涂海燕杨衿记钟文昭李扬秋周清吴一龙 Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhou 510632China Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Chinese Thoracic Oncology Group(CTONG) Guangzhou 510055China Institute of Hematology School of MedicineKey Laboratory for Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510632China

No direct comparison has been performed between different programmed cell death-1(PD-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).The feasibility of using PD-L1-expression-guided immunotherapy remains *** this open-label,phase 2 study(NCT04252365),patients with advanced NSCLC without EGFR or ALK alterations were randomized(1:1)to receive sintilimab or pembrolizumab monotherapy(PD-L1 expression≥50%),or sintilimab or pembrolizumab plus platinum-based chemotherapy(PD-L1 expressionsize was calculated by optimal two-stage *** primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4%(18/35)in the sintilimab *** confirmed ORR(95%confidence interval)was 46.2%(19.2%,74.9%)and 42.9%(17.7%,71.1%)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5%(32.2%,75.6%)and 45.4%(24.4%,67.8%)for those treated with sintilimab-and pembrolizumab-based combination *** median progression-free survival was6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination *** median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination ***-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III ***,the incidence of rash was higher with sintilimab than pembrolizumab *** is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced *** was efficacious and well-tolera

关键词： PD-1 inhibitor Non-small cell lung cancer Pembrolizumab sintilimab PD-L1 expression

Regulation of morphology and visible light-driven photocatalysis of WO_(3)nanostructures by changing pH

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Rare Metals 2021年第7期40卷 1738-1745页

作者： You-Shu Fan Xiao-Li Xi yang-si liu Zuo-Ren Nie Lin-Yan Zhao Qing-Hua Zhang College of Materials Science and Engineering Key Laboratory of Advanced Functional MaterialsEducation Ministry of ChinaBeijing University of TechnologyBeijing 100124China National Engineering Laboratory for Industrial Big-data Application Technology Beijing University of TechnologyBeijing 100124China

The controlled preparation of hexagonal tungsten trioxide(h-WO_(3))nanostructures was achieved by adjusting the pH of the precursor *** effect of the pH on the morphology,elemental composition,and photocatalytic performance of the samples was characterized via X-ray diffraction(XRD),scanning electron microscopy,energy dispersive X-ray spectroscopy,and Raman ***-visible(UV-Vis)spectra were used to evaluate the absorbance and the photocatalytic performance of methylene ***(PL),electrochemical impedance spectroscopy,photocurrent response and Brunauer-Emmett-Teller(BET)were used to study the optical properties,electrical performance,and specific surface area of the WO_(3)-nanostructures,*** results indicate that the WO_(3) nanorods prepared at pH=1.0 exhibit the highest photocatalytic performance(87.4%in 1 h),whereas the WO_(3) nanoblocks prepared at p H=3.0 show the *** photocatalytic performance of the one dimensional(1 D)-nanorods can be attributed to their high specific surface area and charge transfer *** h-WO_(3) nanostructures were synthesized via a simple method and without a capping *** show an excellent photocatalytic performance,which is promising for their application in environment purification.

关键词： h-WO_(3) Morphology pH Photocatalysis Charge transfer Optoelectrical properties

A primer-initiated strand displacement amplification strategy for sensitive detection of 5-Hydroxymethylcytosine in genomic DNA

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Chinese Chemical Letters 2022年第8期33卷 3777-3781页

作者： Yunda Li Yanfei Zhang Zhenning Yu Yuzhi Xu si-yang liu Zong Dai Xiaoyong Zou School of Chemistry Sun Yat-sen UniversityGuangzhou 510275China Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province School of Biomedical EngineeringSun Yat-sen UniversityShenzhen 518107China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China

5-Hydroxymethylcytosine(5 hmC),an intermediate product of DNA demethylation,is important for the regulation of gene expression during development and even *** challenges associated with determination of 5 hm C level include its extremely low abundance and high structural similarity with other cytosine derivatives,which resulted in sophisticated treatment with large amount of sample ***,we developed a primer-initiated strand displacement amplification(PISDA)strategy to quantify the global 5 hm C in genomic DNA from mammalian tissues with high sensitivity/selectivity,low input and simple *** sensitive fluorescence method is based on 5 hmC-specific glucosylation,primer ligation and DNA *** the primer was labeled on 5 hm C site,DNA polymerase and nicking enzyme will repeatedly act on each primer,causing a significant increase of fluorescence signal to magnify the minor difference of 5 hm C content from other cytosine *** method enables highly sensitive analysis of 5 hm C with a detection limit of 0.003%in DNA(13.6 fmol,S/N=3)from sample input of only 150 ng,which takes less than 15 min for *** determination of 5 hmC in different tissues not only confirms the widespread presence of 5 hmC but also indicates its significant variation in different tissues and ***,this PISDA strategy exhibits distinct advantages of bisulfite-free treatment,mild conditions and simple operation without the involvement of either expensive equipment or large amount of DNA *** method can be easily performed in almost all research and medical laboratories,and would provide a promising prospect to detect global 5 hmC in mammalian tissues.

关键词： 5-Hydroxymethylcytosine DNA demethylation Fluorescence detection Strand displacement amplification Enzymatic labeling