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Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

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World Journal of Gastroenterology 2019年第15期25卷 1840-1852页

作者： Gui-Fang Guo Yi-Xing Wang Yi-Jun Zhang Xiu-Xing Chen jia-bin lu Hao-Hua Wang Chang jiang Hui-Quan Qiu Liang-Ping Xia VIP Department Sun Yat-sen University Cancer Center Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Pathology Department Sun Yat-sen University Cancer Center

BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting *** To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type *** ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were *** In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC ***3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three pro

关键词： 4E-binding protein 1 Beclin-1 Microtubule-associated protein 1A/B-light chain 3 Advanced colorectal cancer Cetuximab efficacy Prognosis

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Prognostic impact of splenectomy on advanced proximal gastric cancer with No. 10 lymph node metastasis

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Chinese Medical Journal 2009年第22期122卷 2757-2762页

作者： HUANG Chang-ming WANG jia-bin lu Hui-shan ZHENG Chao-hui LI Ping XIE jian-wei ZHANG Xiang-fu Department of Oncology Affiliated Union Hospital of Fujian Medical University Fuzhou Fujian 350001 China

Background This study evaluated the prognostic impact of D2 lymphadenectomy combined with splenectomy in patients with advanced proximal gastric cancer and lymph node metastasis at the splenic hilum （No. 10 lymph nodes）. Methods The clinical records of 216 patients with advanced proximal gastric cancer and No. 10 lymph node metastasis who underwent D2 curative resection were retrospectively analyzed. Seventy-three patients underwent simultaneous splenectomy （splenectomy group）, while 143 patients did not （spleen-preserving group）. Five-year survival rates, mean numbers of dissected No. 10 lymph nodes and metastatic No. 10 lymph nodes, and operative morbidity and mortality were calculated and compared between the two groups. Potential prognostic factors were evaluated by univariate and multivariate analysis.Results The 5-year survival rate was 30.0% for the splenectomy group and 19.7% for the spleen-preserving group （χ^2=14.73, P 〈0.05）. The mean numbers of dissected No. 10 lymph nodes and metastatic No. 10 lymph nodes in the splenectomy group were significantly greater than in the spleen-preserving group （P 〈0.05）. Multivariate analysis revealed that the depth of invasion, splenectomy, and type of gastrectomy were independent prognostic factors. The survival rate for T3 patients with and without splenectomy was 38.7% and 18.9%, respectively （χ^2 =15.03, P 〈0.05）. For patients undergoing total gastrectomy, survival rates were 33.4% and 20.7%, respectively （χ^2 =13.63, P〈0.05）. Operative morbidity and mortality in splenectomy group was 24.7% and 4.1%, respectively, and in the spleen-preserving group was 17.5% and 3.5%, respectively. The differences were not statistically significant （P 〉0.05）. Conclusions Splenectomy is beneficial for No. 10 lymph node dissection in patients with advanced proximal gastric cancer. To improve patient prognosis, total gastrectomy with splenectomy is recommended for patients with T3 proximal gastric cancer who have No. 10 lymph node met

关键词： stomach neoplasms lymphatic metastasis splenectomy gastrectomy prognosis

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叶身/端壁融合扩压叶栅气动性能实验与数值研究

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工程热物理学报 2017年第8期38卷 1655-1664页

作者：伊卫林李嘉宾季路成北京理工大学大学机械与车辆学院北京100081 北京理工大学大学宇航学院北京100081

已有的数值研究表明叶身/端壁融合设计能有效推迟、减弱或消除压气机角区分离,但实验数据缺乏。为了弥补这一不足,本文针对一42°折转角的NACA65扩压叶栅进行了吸力面叶身/端壁融合设计,并首次在低速平面叶栅风洞中进行了对比实验,证实... 详细信息

已有的数值研究表明叶身/端壁融合设计能有效推迟、减弱或消除压气机角区分离,但实验数据缺乏。为了弥补这一不足,本文针对一42°折转角的NACA65扩压叶栅进行了吸力面叶身/端壁融合设计,并首次在低速平面叶栅风洞中进行了对比实验,证实了叶身/端壁融合扩压叶栅性能提升能力。基于实验结果,进一步校验了RNG-KE、SST等不同湍流模型的模拟精度,并基于SST模型结果揭示了叶身/端壁融合设计的作用机理。实验结果表明:叶身/端壁融合扩压叶栅能在设计攻角及正攻角下改进叶栅性能,提高总压损失系数7%~8%。数值结果表明:融合的加入重新组织了端区流场,避免了流体在叶栅后部吸力面角区内的过度堆积而发生的强三维分离,有效缓解了原型叶栅高损失流动。

关键词：扩压叶栅角区分离叶身/端壁融合风洞实验 CFD

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Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

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Cancer Communications 2020年第1期40卷 3-15页

作者： Qiang-hua Zhou Hui Han jia-bin lu Ting-yu Liu Kang-bo Huang Chuang-zhong Deng Zai-shang Li Jie-ping Chen Kai Yao Zi-ke Qin Zhuo-wei Liu Yong-hong Li Sheng-jie Guo Yun-lin Ye Fang-jian Zhou Ran-yi Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdong510060 P.R.China Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China Department of Urology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Urology Shenzhen People’s HospitalJinan UniversityShenzhenGuangdong 518021P.R.China

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical ***: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation ***: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P luding cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated m

关键词： cytotoxic T-lymphocyte-associated protein 4 immunosuppression indoleamine 2 3-dioxygenase 1 interferon-gamma kynurenine/tryptophan ratio penile cancer programmed cell death protein 1 programmed death-ligand 1 tumor-infiltrating immune cells

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang bin Liu Limin Rong Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei lu bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Understanding the local structure and thermophysical behavior of Mg–La liquid alloys via machine learning potential

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International Journal of Minerals,Metallurgy and Materials 2025年第02期 439-449页

作者： jia Zhao Taixi Feng Guimin lu National Engineering Research Center for Integrated Utilization of Salt Lake Resource East China University of Science and Technology Joint International Laboratory for Potassium and Lithium Strategic Resources East China University of Science and Technology

The local structure and thermophysical behavior of Mg–La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg–La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results; the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg–La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg–La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg–La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg–La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

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Metabolic pathway modulation by olanzapine:Multitarget approach for treating violent aggression in patients with schizophrenia

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World Journal of Psychiatry 2025年第1期15卷 37-53页

作者： Yan-Ning Song Shuang Xia Zhi Sun Yong-Chao Chen lu jiao Wen-Hua Wan Hong-Wei Zhang Xiao Guo Hua Guo Shou-Feng jia Xiao-Xin Li Shi-Xian Cao Li-bin Fu Meng-Meng Liu Tian Zhou Lv-Feng Zhang Qing-Quan jia Department of Pharmacy The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Pharmacy Zhumadian First People's HospitalZhumadian 463000Henan ProvinceChina Scientific Education Section The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Department of Psychiatry The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Clinical Laboratory The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Publicity Division The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina

BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment *** To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent *** Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were *** pharmacology was used to establish protein-protein interaction networks of the core targets of *** Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently *** Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis *** treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with *** effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis *** core targets of olanzapine were involved in several key *** The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.

关键词： Schizophrenia Violent aggression Olanzapine Metabolomics Network pharmacology

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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表面处理水平管外海水降膜蒸发传热的初步实验研究

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水处理技术 2004年第1期30卷 22-25页

作者：马学虎安家明朱晓波陈嘉宾邓新禄大连理工大学化学工程研究所辽宁大连116012 大连理工大学三束材料表面改性国家重点实验室辽宁大连116024

对经处理的表面进行了传热性能测定和表面抗垢特性的考察。考察了淡水和海水在离子镀铬、氮化钛和化学处理水平铝管外表面的降膜传热热性。实验结果表明,经过表面改性处理后的表面可以实现高传热率、耐腐蚀和抗污垢的多重综合功效,对于... 详细信息

对经处理的表面进行了传热性能测定和表面抗垢特性的考察。考察了淡水和海水在离子镀铬、氮化钛和化学处理水平铝管外表面的降膜传热热性。实验结果表明,经过表面改性处理后的表面可以实现高传热率、耐腐蚀和抗污垢的多重综合功效,对于开发新型海水淡化蒸发技术和设备具有重要的意义。但是表面处理的工艺条件需作进一步的研究和分析,以期实现在较长时期内的稳定工作的需要。

关键词：表面处理铝管海水淡化降膜蒸发传热率水资源

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