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| 1 | Prevalence, risk factors, and survival associated with pulmonary hypertension and heart failure among patients with underlying coronary artery disease: a national prospective, multicenter registry study in China显示文摘Background: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Methods: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.Results: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF];left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF];LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.Conclusions: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.Trial Registration: ClinicalTrials.gov, NCT02164526. | Li Huang Lingpin Pang Qing Gu Tao Yang Wen Li Ruilin Quan Weiqing Su Weifeng Wu Fangming Tang Xiulong Zhu Jieyan Shen Jingzhi Sun Guangliang Shan Changming Xiong Shian Huang Jianguo He | 2022 | Chinese Medical Journal2022，，15： | 4 |
| 2 | The establishment of polypeptide PSMA-targeted chimericantigen receptor-engineered natural killer cells forcastration-resistant prostate cancer and the induction of ferroptosis-related cell death显示文摘Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective treatment.Chimeric antigen receptor(CAR)-based therapy is a promising immunotherapeutic strategy.Here,we aimed to design a novel CAR-natural killer(NK)cells with a clinically significant tumoricidal effect on CRPC.Methods:We constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral vector.Different intracellular segments(CD244,NKG2D,or CD3ζ)were screened to identify the best candidate according to cell lysis assay and CD107a expression levels.To enhance the affinity of the CAR to the tumor antigen,we compared an antibody specific for prostate-specific membrane antigen(anti-PSMA)with PSMA-targeted polypeptide(p-PSMA),which was screened by phage display combinatorial library.Then,CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated.In addition,we verified their tumor-killing effect in vitro and in vivo.The release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent assay.Moreover,ferroptosis-related cell death was explored as a possible underlying mechanism.Results:Three different CAR intracellular regions CAR1(CD244),CAR2(CD244,NKG2D)and CAR3(CD244,NKG2D,and CD3ζ)were constructed.CAR2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI cells.Compared with anti-PSMA,p-PSMA exhibited enhanced affinity for the tumor antigen.Thus,p-PSMA-CAR-NK92MI cells,which expressed CAR with a polypeptide-based antigen-binding region,an intracellular CD244 and a NKG2D costimulatory domain,were generated.They could selectively and successfully kill PSMA+target cells and exhibited specific lysis rate of 73.19%for PSMA-positive C4-2 cells and 33.04%for PSMA-negative PC3 cells.Additionally,p-PSMA-CAR-NK92MI cells had significantly higher concentrations of IFN-γ,TNF-αand granzyme B than NK92MI cells.In a CRPC cancer xenograft model,p-PSMA-CAR-NK92MI cells significantly inhibited tumor growth and exerted a more consistent killing effect than NK92MI cells.Moreover,ferroptosis is a potential mechanism through which CAR-NK92MI cells attack cancer cells,and is triggered by IFN-γ.Conclusions:p-PSMA-CAR-NK92MI cells can effectively kill CRPCPSMA+cells in vitro and in vivo.This strategy may provide additional treatment options for patients with CRPC. | Liyuan Wu Fei Liu Le Yin Fangming Wang Hui Shi Qinxin Zhao Feiya Yang Dong Chen Xiying Dong Yuchun Gu Nianzeng Xing | 2022 | Cancer Communications2022，42，8： | 2 |
| 3 | Memory access integrity:detecting fine-grained memory access errors in binary code显示文摘As one of the most notorious programming errors,memory access errors still hurt modern software security.Particularly,they are hidden deeply in important software systems written in memory unsafe languages like C/C++.Plenty of work have been proposed to detect bugs leading to memory access errors.However,all existing works lack the ability to handle two challenges.First,they are not able to tackle fine-grained memory access errors,e.g.,data overflow inside one data structure.These errors are usually overlooked for a long time since they happen inside one memory block and do not lead to program crash.Second,most existing works rely on source code or debugging information to recover memory boundary information,so they cannot be directly applied to detection of memory access errors in binary code.However,searching memory access errors in binary code is a very common scenario in software vulnerability detection and exploitation.In order to overcome these challenges,we propose Memory Access Integrity(MAI),a dynamic method to detect finegrained memory access errors in off-the-shelf binary executables.The core idea is to recover fine-grained accessing policy between memory access behaviors and memory ranges,and then detect memory access errors based on the policy.The key insight in our work is that memory accessing patterns reveal information for recovering the boundary of memory objects and the accessing policy.Based on these recovered information,our method maintains a new memory model to simulate the life cycle of memory objects and report errors when any accessing policy is violated.We evaluate our tool on popular CTF datasets and real world softwares.Compared with the state of the art detection tool,the evaluation result demonstrates that our tool can detect fine-grained memory access errors effectively and efficiently.As the practical impact,our tool has detected three 0-day memory access errors in an audio decoder. | Wenjie Li Dongpeng Xu WeiWu Xiaorui Gong Xiaobo Xiang Yan Wang Fangming gu Qianxiang Zeng | 2019 | Cybersecurity2019，2，1： | 1 |
| 4 | Memory access integrity:detecting fine-grained memory access errors in binary code显示文摘As one of the most notorious programming errors,memory access errors still hurt modern software security.Particularly,they are hidden deeply in important software systems written in memory unsafe languages like C/C++.Plenty of work have been proposed to detect bugs leading to memory access errors.However,all existing works lack the ability to handle two challenges.First,they are not able to tackle fine-grained memory access errors,e.g.,data overflow inside one data structure.These errors are usually overlooked for a long time since they happen inside one memory block and do not lead to program crash.Second,most existing works rely on source code or debugging information to recover memory boundary information,so they cannot be directly applied to detection of memory access errors in binary code.However,searching memory access errors in binary code is a very common scenario in software vulnerability detection and exploitation.In order to overcome these challenges,we propose Memory Access Integrity(MAI),a dynamic method to detect finegrained memory access errors in off-the-shelf binary executables.The core idea is to recover fine-grained accessing policy between memory access behaviors and memory ranges,and then detect memory access errors based on the policy.The key insight in our work is that memory accessing patterns reveal information for recovering the boundary of memory objects and the accessing policy.Based on these recovered information,our method maintains a new memory model to simulate the life cycle of memory objects and report errors when any accessing policy is violated.We evaluate our tool on popular CTF datasets and real world softwares.Compared with the state of the art detection tool,the evaluation result demonstrates that our tool can detect fine-grained memory access errors effectively and efficiently.As the practical impact,our tool has detected three 0-day memory access errors in an audio decoder. | Wenjie Li Dongpeng Xu WeiWu Xiaorui Gong Xiaobo Xiang YanWang Fangming gu Qianxiang Zeng | 2018 | Cybersecurity2018，1，1： | 0 |
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