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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen xianyang wang Qing xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China Department of Biology School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most *** such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical *** antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic ***,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune ***,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 ***,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under ***-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of *** review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： Immunotherapy cancer ICIs PD-1 CTLA-4

Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota

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Food Science and Human Wellness 2024年第2期13卷 1093-1107页

作者： Yu xi Wenhui Li Junru wang Meihong Yu xiangquan Zeng He Li Jian Li Key Laboratory of Green and Low-Carbon Processing Technology for Plant-Based Food of China National Light Industry Council Beijing Advanced Innovation Center for Food Nutrition and Human HealthBeijing Technology and Business UniversityBeijing 100048China

Trimethyltin chloride(TMT)is a potent neurotoxin to cause neurodegeneration,especially in *** study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in *** predominant anthocyanin in human diets,cyanidin-3-O-glucoside(C3G,5 or 50 mg/kg),was given to mice for 16 days,and TMT(2.7 mg/kg)was injected intraperitoneally once on the eighth day.C3G(50 mg/kg)significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic ***,C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase(GS)inhibition in reactive astrogliosis and neuroinflammation,which are critical for C3G's neuroprotective ***,C3G decreased the lipopolysaccharide,tumor necrosis factor-α,interleukin-6,and interleukin-1βlevels in the mice,which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut.C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.

关键词： Cyanidin-3-O-glucoside Trimethyltin Neurodegeneration Glutamatergic pathway Gut microbiota

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2438-2444页

作者： Bi-Yu Zhang Mou-wang Liang Shuang-xi Zhang Department of Gastroenterology Guangzhou University of Chinese Medicine Shunde HospitalFoshan 528300Guangdong ProvinceChina Department of Gastroenterology Guangzhou University of Chinese MedicineGuangzhou 510006Guangdong ProvinceChina

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated *** studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of *** SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 *** pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic *** was difficult to distinguish between inflammation and *** immunoglobulin G4(IgG4)was markedly ***4 is an important serological marker for type 1 *** patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic *** applying hormonal therapy,the patient's symptoms improved *** the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators *** treatment was *** In patients with pancreatic swelling,the possibility of AIP should be considered.

关键词： Autoimmune pancreatitis Characteristics Diagnosis Immunoglobulin G4 Case report

Evaluation of the Relative Tectonic Activity from the Faults in the Gengma-Lancang-Menghai Seismic Belt(Southwestern China)

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Journal of Earth Science 2024年第1期35卷 131-143页

作者： Dan wang Youpu Dong Zhipeng xi Dongyue Zhang Jiaxin Duan Huayu Yu Liang Yu Faculty of Land Resource Engineering Kunming University of Science and TechnologyKunming 650093China

The Gengma-Lancang-Menghai seismic belt,the southernmost part of the North-South seismic belt,is controlled by four active faults:the Nantinghe fault(NTHF),the Sanjianshan fault(SJSF),the Hanmuba-Lancang fault(HMB-LCF),and the Heihe fault(HHF),from northwest to ***,the tectonic activity of the faults in the Gengma-Lancang-Menghai seismic belt has not been fully studied *** the present work,we conducted tectonic geomorphic indices to analyze the relative tectonic activity along the faults in the seismic belt based on the digital elevation *** interpreted asymmetric factor,index of drainage basin shape,hypsometric integral,normalized streamlength gradient,valley floor-to-width to height ratio,and longitudinal profiles to show that the relative tectonic activity is higher in the north and lower in the south,and is strong in the region from Shanjia to Huimin in the center of the seismic belt.

关键词： Gengma-Lancang-Menghai seismic belt southeastern Tibetan Plateau geomorphic indices longitudinal profile

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

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World Journal of Psychiatry 2024年第6期14卷 894-903页

作者： Dan-Dan wang Hong-Yu wang Yan Zhu xi-Hua Lu Department of Anesthesiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008Henan ProvinceChina

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal ***,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain *** To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient *** This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January *** receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,*** compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after *** levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after *** Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after *** reactions were also *** There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest

关键词： Thoracic paravertebral block Sufentanil Thoracoscope Radical resection of lung cancer Postoperative cognitive dysfunction

Discrepant responses of soil organic carbon dynamics to nitrogen addition in different layers: a case study in an agroecosystem

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Frontiers of Agricultural Science and Engineering 2024年第2期11卷 314-325页

作者： Hualing HU Liang ZHAO Wenbing TAN Guoan wang Beidou xi Technical Centre for Soil Agriculture and Rural Ecology and EnvironmentMinistry of Ecology and EnvironmentBeijing 100012China State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China College of Resources and Environmental Sciences China Agricultural UniversityBeijing 100193China

Empirical research indicates that heightened soil nitrogen availability can potentially diminish microbial decomposition of soil organic carbon(SOC).Nevertheless, the relationship between SOC turnover response to N addition and soil depth remains unclear. In this study, soils under varying N fertilizer application rates were sampled up to 100 cm deep to examine the contribution of both new and old carbon to SOC across different soil depths,using a coupled carbon and nitrogen isotopic approach. The SOC turnover time for the plot receiving low N addition(250 kg·ha^(-1)·yr^(-1) N) was about 20-40 years. Conversely, the plot receiving high N(450 kg·ha^(-1)·yr^(-1) N) had a longer SOC turnover time than the low N plot, reaching about 100 years in the upper 10-20 cm layer. The rise in SOC over the entire profile with low N addition primarily resulted from an increase in the upper soil(0-40 cm)whereas with high N addition, the increase was mainly from greater SOC in the deeper soil(40-100 cm). Throughout the entire soil layer, the proportion of new organic carbon derived from maize C_4 plant sources was higher in plots treated with a low N rate than those treated with a high N rate. This implies that, in contrast to low N addition agricultural practices, high N addition predominantly enhances the soil potential for fixing SOC by transporting organic matter from surface soils to deeper layers characterized by more stable properties. This research offers a unique insight into the dynamics of deep carbon under increased N deposition, thereby aiding in the formulation of policies for soil carbon management.

关键词： ^(13)C natural abundance nitrogen addition soil depth organic carbon turnover

Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

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Journal of Geriatric Cardiology 2024年第1期21卷 90-103页

作者： Cheng-Yan HU Yan-Ling wang Zhen-xing FAN xi-Peng SUN Shuai wang Zhi LIU Department of Geriatrics Fu Xing HospitalCapital Medical UniversityBeijingChina Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Emergency Department of Xuanwu Hospital Capital Medical UniversityBeijingChina

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were *** on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up *** were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 *** aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel *** cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were *** CLR was observed in 44.4%of the overall *** differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene ***2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

关键词： CYP2C19 drugs PCI

A hierarchical multi-UAV cooperative framework for infrastructure inspection and reconstruction

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Control Theory and Technology 2024年第3期22卷 394-405页

作者： Chuanxiang Gao xinyi wang xi Chen Ben M.Chen Department of Mechanical and Automation Engineering The Chinese University of Hong KongHong KongShatinNTChina

Unmanned aerial vehicles(UAVs)are emerging as a powerful tool for inspections and repair works in large-scale and unstructured 3D infrastructures,but current approaches take a long time to cover the entire *** using UAVs for inspections and repair works puts forward a requirement of improving time efficiency in large-scale and cluster *** paper presents a hierarchical multi-UAV cooperative framework for infrastructure inspection and reconstruction to balance the workload and reduce the overall task completion *** proposed framework consists of two stages,the exploration stage and the exploitation stage,resolving the task in a sequential *** the exploration stage,the density map is developed to update global and local information for dynamic load-balanced area partition based on reconstructability and relative positions of UAVs,and the Voronoi-based planner is used to enable the UAVs to reach their best *** obtaining the global map,viewpoints are generated and divided while taking into account the battery capacity of each ***,a shortest path planning method is used to minimize the total traveling cost of these viewpoints for obtaining a high-quality *** experiments are conducted in both a simulated and real environment to show the time efficiency,robustness,and effectiveness of the proposed ***,the whole system is implemented in real applications.

关键词： Multi-UAV Coverage path planning Infrastructure inspection and reconstruction

Dynamic recrystallization behavior and strengthening mechanism of a novel Mo-Ti_(3)AlC_(2) alloy at ultrahigh temperature

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Rare Metals 2024年第8期43卷 3946-3960页

作者： Lu Yang xin-Yuan Zheng Yang Zhao xi-Ran wang Fang-Nao xiao Shi-Zhong Wei School of Materials Science and Engineering Henan University of Science and TechnologyLuoyang 471023China National Joint Engineering Research Center for Abrasion Control and Molding of Metal Materials Henan University of Science and TechnologyLuoyang 471003China Department of Applied Mechanics Univ.Bourgogne FrancheComteFEMTO-ST InstituteCNRS/UF/ENSMM/UTBM25000BesangonFrance

Increasing the recrystallization temperature to achieve better high-temperature performance is critical in the development of molybdenum alloys for ultrahightemperature applications,such as the newest generation of multitype high-temperature nuclear *** this study,an innovative strategy was proposed to improve the performance of molybdenum alloys at high temperature by using the two-dimensional MAX(where M is an early transition metal,A is an A-group element and X is C or N)ceramic material Ti_(3)AlC_(2).The relationships between flow stress,strain rate and temperature were *** microstructure,distribution of misorientation and evolution of dislocations in the Mo-Ti_(3)AlC_(2) alloy were *** microscopic mechanism of the Ti_(3)AlC_(2) phase in the molybdenum alloy at high temperatures was *** experimental results showed that the peak flow stress of Mo-Ti_(3)AlC_(2) at 1600℃ reached 155 MPa,which was161.8% greater than that of pure *** activation energy of thermal deformation of Mo-Ti_(3)AlC_(2) was as large as537 kJ·mol~(-1),which was 17.6% more than that of pure *** recrystallization temperature reached 1600℃ or even *** topological reaction of the Ti_(3)AlC_(2) phase consumed a large amount of energy at high temperatures,resulting in increases in the deformation activation *** structures of AlTi_3 and Ti-O Magneli-phase oxides(Ti_nO_(2n-1)) were formed in-situ,which relied on kink bands and interlayer slip,resulting in many dislocations during ***,the special two-dimensional of the structure Ti_(3)AlC_(2) ceramic inhibited the recrystallization behavior of the Mo *** results of this study can provide theoretical guidance for the development of a new generation of molybdenum alloys for use in ultrahigh-temperature environments.

关键词： Mo alloy Two-dimensional reinforcement Dynamic recrystallization behavior Hot deformation Mechanical properties