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Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm

Chinese Journal of Integrative Medicine 2024年第11期30卷 993-1000页

作者： XU Yu-ying LI Qiu-yan YI Dan-hui CHEN Yue ZHAI Jia-wei ZHANG Tong sun Ling-yun YANG Yu-fei Department of Oncology Xiyuan Hospital China Academy of Chinese Medical Sciences School of Statistics Renmin University of China Graduate School Beijing University of Chinese Medicine

Objective: To establish the dynamic treatment strategy of Chinese medicine(CM) for metastatic colorectal cancer(m CRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for m CRC. Methods: From the outpatient cases of m CRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment(CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment(CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for m CRC was explored based on the cost-sensitive classification learning algorithm for survival(CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. Results: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for m CRC was established based on *** CM intervention strategies for m CRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the modelrecommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months(P=0.06). Conclusions:

关键词： Chinese medicine cost sensitive classification learning for survival dynamic treatment strategy metastatic colorectal cancer

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Revisit of GeV Gamma-Ray Emission from Orion B with the Fermi Large Area Telescope

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Research in Astronomy and Astrophysics 2024年第9期24卷 128-135页

作者： Wei Zeng Xiao-Na sun Rui-Zhi Yang Jia-Chun He Zhao-Dong Shi Ting-Ting Ge yun-Feng Liang En-Wei Liang Guangxi Key Laboratory for Relativistic Astrophysics School of Physics Science and TechnologyGuangxi UniversityNanning 530004China Department of Astronomy School of Physical SciencesUniversity of Science and Technology of ChinaHefei 230026China CAS Key Labrotory for Research in Galaxies and Cosmology University of Science and Technology of ChinaHefei 230026China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China

We revisit the γ-ray emission above 300 Me V towards the massive star-forming region of Orion B by adopting14 yr observations with the Fermi Large Area Telescope and utilizing the updated software *** extended γ-ray emission region around Orion B is resolved into two components(region Ⅰ and region Ⅱ).The γ-ray spectrum of region I agrees with the predicted γ-ray spectrum assuming the cosmic ray(CR)density is the same as that of Alpha Magnetic Spectrometer(AMS-02)measured ***γ-ray emissivity of region II appears to be deficit at low energy band(E<3 GeV).Through modeling we find that CR densities exhibit a significant deficit below 20 Ge V,which may be caused by a slow diffusion inside the dense *** is probably caused by an increased magnetic field whose strength increases with the gas density.

关键词： (ISM:)cosmic rays gamma-rays:ISM (Galaxy:)open clusters and associations:individual(NGC 2023 NGC 2024 NGC 2068 and NGC 2071)

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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi sun Lin Huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to *** dysregulation of double-negative(DN)T cells is considered as a crucial commander during ***,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune ***,the function of neddylation in SLE is still ***,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus *** investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus *** double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus *** findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus ***,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was ***,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation ***,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE ***,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

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A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 102-114页

作者： Cuixia Zheng Lingling sun Hongjuan Zhao Mengya Niu Dandan Zhang Xinxin Liu Qingling Song Weijie Zhong Baojin Wang yun Zhang Lei Wang School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Huaihe Hospital of Henan University Translational medicine CenterKaifeng 475000China Pingyuan Lab Henan Normal UniversityXinxiang 453007China Gynecology the Third Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Weihai Municipal Hospital Cheeloo College of MedicineShandong UniversityWeihai 264200China

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting ***,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial ***,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing *** this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer *** detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/*** tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·*** combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune ***,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune *** this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and *** summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

关键词： Biomimetic spore shell Bacteria-mediated antitumor therapy Chemodynamic therapy immunotherapy Tumor microenvironment

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Plant-microbial interactions inspired the discovery of novel sesquiterpenoid dimeric skeletons of hidden natural products from Hibiscus tiliaceus

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Chinese Chemical Letters 2024年第10期35卷 286-290页

作者： Deli Chen Jiawen Li Xudong Xu Zhaocui sun yun Yang Minghui Xu Hanqiao Liang Junshan Yang Hui Meng Guoxu Ma Jianhe Wei Hainan Branch of the Institute of Medicinal Plant Development(Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine) Chinese Academy of Medical Sciences&Peking Union Medical CollegeHaikou 570311China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China School of Pharmaceutical Science Hainan Medical UniversityHaikou 571199China Department of Biomedicine Beijing City UniversityBeijing 100094China

Hidden natural products are representative of defensive strategies produced in vivo in diseased plants,a process that is induced by the plant immune *** first transcriptome library of uninfected and pathogen infected Hibiscus tiliaceus stems was constructed by transcriptome sequencing technology,genes related to cadinene-type sesquiterpenoid biosynthesis were screened and combined with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-QTOF-MS)analysis data,which indicated pathological tissue had potential to produce novel carbon skeletons of cadinane sesquiterpenoid ***,two cadinane-derived sesquiterpenoid dimers with unprecedented carbon skeletons,hibisceusanols A(1)and B(2)were isolated for the first time from the stems of *** induced by plant-microbial *** structures and absolute configurations were unambiguously established by spectroscopy,advanced chemistry development(ACD)and electronic circular dichroism(ECD)*** 1 and 2 exhibited significant antitumor activity in vitro with half maximal inhibitory concentration(IC_(5)0)values of 2.3–7.2μmol/*** anticancer effect was generated via the induction of Hep G2 cell apoptosis by inhibiting the phosphatidylinositol 3-kinase(PI3K)pathway.

关键词： Cadinane-derived sesquiterpenoid Anti-cancer PI3K Plant-microbial interactions

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Bioinformatics comprehensive analysis confirmed the potential involvement of SLC22A1 in lower-grade glioma progression and prognosis

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BIOCELL 2024年第5期48卷 803-815页

作者： JING HUI NANA sun YONG LIU CHUNBO YU YONG KE YONG CAO ANXIAO YU QINGHONG KONG yun LIU Guizhou Provincial College-Based Key Lab for Tumor Prevention and Treatment with DistinctiveMedicines Zunyi Medical UniversityZunyi563000China College of Basic Medicine Zunyi Medical UniversityZunyi563000China Department of Dermatology Guizhou Province Cosmetic Plastic Surgery HospitalAffiliated Hospital of Zunyi Medical UniversityZunyi563000China School of Forensic Medicine Zunyi Medical UniversityZunyi563000China

Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains ***:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various *** of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)***:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(pimportantly,we found the potential involvement of SLC22A1 in occurrence and progress of certain cancers,with a pronounced impact on *** examination of the SLC22A1-LGG relationship revealed its status as an independent risk factor for LGG,suggesting its potential involvement in regulating diverse immune pathways and metabolic *** Glioma Genome Atlas(CGGA)data supported the reliability of the risk score as a prognostic and recurrence indicator,emphasizing the accuracy of the nomograph(1,3,and 5-year-AUC>0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell ***:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG ***22A1 has only been proved to support cellular function *** findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of ***,we provide a highly practical prediction model for estimating the survival rate of LGG patients.

关键词： SLC22A1 LGG prognosis immune nomogram

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Insights into dammarane-type triterpenoid saponin biosynthesis from the telomere-totelomere genome of Gynostemma pentaphyllum

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Plant Communications 2024年第8期5卷 100-103页

作者： Lingling yun Chuyi Zhang Tongtong Liang Yu Tian Guoxu Ma Vincent Courdavault Sijie sun Baiping Ma Ziqin Li Rucan Li Feng Cao Xiaofeng Shen Jianhe Wei Ying Li Baolin Guo Chao sun Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100193China Biomole cules et Biotechnologies Ve ge tales EA2106Universite de Tours37200 ToursFrance Beijing Institute of Radiation Medicine Beijing 100850China Present address:National Genomics Data Center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Dear Editor,Gynostemma pentaphyllum(Thunb.)Makino,a perennial climbing vine in the Cucurbitaceae family,has been widely used in traditional medicine for over 600 years(Blumert and Liu,1999).It serves as a valuable natural source of over 200 dammaranetype saponins with notable bioactive properties,including anti-cancer,cardioprotective,hepatoprotective,neuroprotective,and anti-diabetic activities(Li et al.,2016;Nguyen et al.,2021).

关键词： protective Gynostemma saponins

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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-yun Zhou Jie Sheng Lei Zhao yun-Xin Zhu Jing sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Hyperlanins A and B, Two Highly Rearranged Meroterpenoids from Hypericum lancasteri

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Chinese Journal of Chemistry 2024年第18期42卷 2180-2186页

作者： Jin-Qiu You yun-Qi Jin Meng-Yu Li Bo-Chao Zhang Xin-Yu sun Chun-Yong Ding Jing-Ya Li Ai-Jun Hou Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical SciencesShanghai Jiao Tong UniversityShanghai200240China National Key Laboratory of Innovative immunotherapy Shanghai Jiao Tong UniversityShanghai 200240China Shanghai Jiao Tong University School of Medicine Shanghai 200025China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China

Hyperlanins A(1)and B(2),two highly rearranged polycyclic polyprenylated acylphloroglucinol(PPAP)-related meroterpenoids based on different new carbon skeletons,were isolated from Hypericum *** 1 incorporates an unprecedented 5/6/7/5 ring system featuring a 3,13-dioxatetracyclo[9.***.1.12.5.01.8]pentadecane *** 2 possesses a unique compact 6/6/5/6/6/5/6 ring system with a caged tetracyclo[6.***.1.13.8.05,11]dodecane *** structures were established by spectroscopic data,X-ray diffraction,and computational *** compounds showed anti-inflammatory activity in *** 1 and 2 could decrease the lipopolysaccharide(LPS)-/nigericin-induced IL-1βrelease in THP-1 *** compounds also showed inhibition in hypoxia-inducible factor-1α(HIF-1αa)pathway luciferase reporter assay.

关键词： Natural products Hypericum lancasteri Meroterpenoids Structureelucidation Inflammation

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun yun Hyeon-Ju Jeong Eun-Ju Jin yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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