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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and Experimental medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National Center of Stomatology BeijingChina National Clinical research Center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina Peking university International Cancer institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering research Center of Oral Biomaterials and Digital medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone ***,current anti-resorptive drugs carry a risk of various *** deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression *** study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone ***:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary ***-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also *** underlying mechanism was verified using qRT-PCR,western blot(WB),immunofluorescence(IF),***:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of *** BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting ***:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

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De-qi,Not Psychological Factors,Determines the Therapeutic Efficacy of Acupuncture Treatment for Primary Dysmenorrhea

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Chinese Journal of Integrative medicine 2012年第1期18卷 7-15页

作者：熊瑾刘芳张明敏王伟黄光英 institute of integrated traditional and western medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

Objective： To study the impact of De-qi （得气%, obtaining qi） and psychological factors on the efficacy of acupuncture treatment for primary dysmenorrhea, with an attempt to explore the relationship among De-qi, psychological factors, and clinical efficacy. Methods： The patients with primary dysmenorrhea were randomly assigned to a group of acupuncture with manual manipulation （manipulation group, n=67） and an acupuncture group without manipulation （non-manipulation group, n=64）. Pain intensity and pain duration were used as measures for evaluating the therapeutic efficacy of the acupuncture treatment. De-qi, the sensations a patient experienced during the acupuncture treatment, was scored on a 4-point scale by the subjects. In addition, the psychological factors, including belief in acupuncture, the level of nervousness, anxiety, and depression, were quantitatively assessed. The personality of the subject was assessed using the Eysenck personality questionnaire （EPQ） and 16 personality factor questionnaire （16PF）. Results： Complete data were obtained from 120 patients, 60 patients in each group. There were statistically significant differences in pain intensity （W=2410.0, P〈0.01 ） and pain duration （W=3181.0, P〈0.01） between the two groups. The number of De-qi acupoints （W=1150.5, P〈0.01） and the average intensity of De-qi （W=1141.0, P〈0.01） were significantly higher in the manipulation group as compared with their non-manipulation counterparts. The correlation coefficients between De-qi and therapeutic efficacy of acupuncture were greater than those between psychological factors and therapeutic efficacy. Conclusions： Compared with the psychological factors, De-qi contributed more to the pain-relieving effect of acupuncture in subjects with primary dysmenorrhea. Moreover, manual manipulation is a prerequisite for eliciting and enhancing the De-qi sensations, and De-qi is critical for achieving therapeutic effects.

关键词： acupuncture De-qi psychological factors manual acupuncture needle manipulation therapeuticefficacy primary dysmenorrhea

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Neuroprotective mechanism of Kai Xin San: upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation

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Neural Regeneration research 2017年第4期12卷 654-659页

作者： Na Wang Yong-ming Jia Bo Zhang Di Xue Maharjan Reeju Yan Li Shu-ming Huang Xue-wei Liu institute of medicine Qiqihar Medical University Department of Neuroscience Institute of Traditional Chinese MedicineHeilongjiang University of Chinese Medicine

Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β （Aβ） induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme （IDE）, which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 （200 μM, 5 μL） into the hippocampus and subsequently administered Kai Xin San （0.54 or 1.08 g/kg/d） intragastrically for 21 consecutive days. Hematoxylin eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.

关键词： nerve regeneration neurodegeneration traditional Chinese medicine Kai Xin San insulin-degrading enzyme amyloid-β Alzheimer'sdisease Chinese herbal compound Aβ-degrading enzymes neurons Radix Ginseng Radix Polygalae Acorus Tatarinowii Rhizoma neuralregeneration

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Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer

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Journal of Integrative medicine 2021年第5期19卷 408-417页

作者： Hao Gou Ruo-chen Huang Fu-lei Zhang Yong-hua Su Department of traditional Chinese medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Internal medicine Tianjin Binhai New Area Hospital of TCMFourth Teaching Hospital of Tianjin University of TCMTianjin 300451China International Joint Cancer institute Naval Medical UniversityShanghai 200433China Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai 201203China

Objective: Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor watersolubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these ***: A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles(DTIs) loaded with bufalin(DTIs–BF)were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs–BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration(CMC), entrapment efficiency(EE), drug release and non-cytotoxicity of blank block copolymer micelles(BCMs) were evaluated. Next, the effects of DTIs–BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs–fluorescein isothiocyanate(FITC) and the in vivo anti-tumor effect were observed using an interactive video information ***: DTIs–BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs–BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 ℃ than 37 ℃. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs–FITC were injected intravenously in BALB/c nude mice bearing liver cancer,the accumulation of FITC was significantly increased in ***: DTIs–BF is a potentially effective nano-formulation and has broad prospects in the cl

关键词： Bufalin Liver cancer Epidermal growth factor receptor Immunomicelles

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Psychological Factors Are Closely Associated with the Bell's Palsy: A Case-control Study

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Journal of Huazhong university of Science and Technology(medical Sciences) 2012年第2期32卷 272-279页

作者：黄波徐沙贝熊瑾黄光英张旻王伟 Department of Neurology and Psychology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology institute of integrated traditional and western medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

To observe the differences in psychological status between Bell’s palsy (BP) patients and healthy subjects, and to examine the relationship between psychological factors and the severity of BP, we conducted a case-control, multi-center clinical investigation. A total of 695 subjects were assigned to the case group (n=355) and the control group (n=340). House–Brackmann grading system and Facial Disability Index (FDI) were adopted to assess the BP patients; Kessler Psychological Distress Scale (K10) and 16 Personality Factor (16PF) scale were employed to evaluate the psychological distress and personality profiles of all subjects. Two independent samples t test was used to compare the differences between cases and controls, and to compare the differences among different BP patients. Pearson correlation analysis was used to examine the relationship between psychological factors and severity of facial paralysis. The results showed that psychological distress (K10) in case group (27.09±5.80) was significantly higher than that in control group (13.43±3.02) (t=–37.219, P=0.000). The scores of personality factor Warmth (A), Openness to Change (Q1), Self-Reliance (Q2) were lower in cases than in the controls (P<0.01, P<0.05, P<0.05, respectively), whereas the scores of Sensitivity (I), Vigilance (L), Apprehension (O), and Tension (Q4) were significantly higher in cases than in the controls (P<0.05, P<0.01, P<0.01, P<0.01, respectively). In addition, the psychological distress was significantly higher in female patients, severe (HB score Ⅳ–Ⅵ) patients, and subacute (onset time 72–168 h) patients compared with that in male patients, mild (HB score Ⅰ–Ⅲ)patients, and acute (onset time≤72 h) patients (P<0.05). The scores of personality factor in female patients, severe patients, and subacute patients were also significantly different from male patients, mild patients, and acute patients (P<0.05). The result of Pearson correlation analysis showed that psychological factors (K10, p

关键词： Bell’s palsy psychological distress personality factor

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Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria:a randomized placebo-controlled trial

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Journal of Integrative medicine 2013年第3期11卷 175-183页

作者： Tian-zhan Wang Yu Chen Yan-ming He Xiao-dong Fu Yi Wang Yan-qiu Xu Hong-jie Yang Hong-li Xue Yi Liu Xiao-tao Feng Teng Zhang Wen-jian Wang institute of Integrative medicine Huashan HospitalFudan University Yueyang Hospital of integrated traditional Chinese and western medicine Shanghai University of Traditional Chinese Medicine Clinical research institute of Integrative medicine Shanghai University of Traditional Chinese Medicine Guangxi Scientifc Experimental Center of traditional Chinese medicine Guangxi University of Chinese Medicine

BACKGROUND： Microalbuminuria （MAU） is a key component of metabolic syndrome （MetS） and is an early sign of diabetic nephropathy as well. Although routine western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE： To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： Sixty patients with MetS were randomized into the Chinese herbal formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with western medicine） and control group （placebo in combination with western medicine）. All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES： Urinary microalbumin （MA）, urinary albumin-to-creatinine ratio （UACR）, 24-hour total urine protein （24-hTP）, body mass index （BMI）, waist circumference （WC）, waist-to-hip ratio （WHR）, fasting plasma glucose （FPG）, 2-hour postprandial plasma glucose （2-hPPG）, glycosylated hemoglobin （HbAlc）, homeostasis model assessment for insulin resistance （HOMA-IR）, blood lipid profile and blood pressure were observed. RESULTS： Compared with the control group, CHF treatment significantly decreased BMI （P〈0.05）, WC （P〈0.01） and WHR （P〈0.01）. Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment （P〈0.05）. Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol （TAG）, and a greater reduction in TAG was observed with CHF treatment （P〈0.05）. The level of high-density lipoprotein cholesterol did not change in the control group after treatment

关键词： metabolic syndrome X microalbuminuria insulin resistance drugs, Chineseherbal randomized controlled trials

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Effects of baicalin in CD4 + CD29 + T cell subsets of ulcerative colitis patients

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World Journal of Gastroenterology 2014年第41期20卷 15299-15309页

作者： Feng-Yan Yu Shao-Gang Huang Hai-Yan Zhang Hua Ye Hong-Gang Chi Ying Zou Ru-Xi Lv Xue-Bao Zheng traditional Chinese medicine institute Guangdong medical College Guangdong Provincial Hospital of university City Branch traditional Chinese medicine institute Guangdong medical College Guangdong Key Laboratory of Natural Medicine Research and Development School of traditional Chinese medicine of Southern medical College

AIM: To evaluate the role of baicalin in ulcerative colitis (UC) with regard to the CD4+CD29+ T helper cell, its surface markers and serum inflammatory cytokines.

关键词： Ulcerative colitis Baicalin CD4+CD29+ Cytokines Nuclear factor-κ B

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Qingnaoyizhi decoction suppresses the formation of glial fibrillary acidic protein-positive cells in cultured neural stem cells by inhibiting the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

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Journal of traditional Chinese medicine 2015年第1期35卷 69-76页

作者： Wu Yanqing Jing Zhiwei Qin Xiude Zhou Zhen Wang Kai Song Wanshan Wang Xueyan Hou Mengmeng Zhang Yulian Kang Liyuan institute of traditional Chinese medicine Tianjin University of Traditional Chinese Medicine Department of Neurology the Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine institute of Clinical Foundational Chinese medicine China Academy of Chinese Medical Sciences

OBJECTIVE: Inactivation of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) signaling axis plays a crucial role in determining the fate of neural stem cells(NSCs).Qingnaoyizhi decoction(QNYZD) has been used for the treatment of vascular dementia and has shown to improve synaptic remodeling. The aim of this study was to evaluate the effect of cerebrospinal fluid(CSF) containing QNYZD(CSF-QNYZD) on the differentiation of cultured NSCs and the involvement of the JAK2/STAT3 ***: The protein expression levels of glial fibrillary acidic protein(GFAP), tubulin, drosophila mothers against decapentaplegic protein(SMAD-1), STAT3, and phosphorylated-STAT3 were detected by western immunoblot analysis in the groups: control, CSF, JAK/STAT inhibitor(AG490),CSF-QNYZD, and CSF-XDZ(CSF-Xidezhen). The differentiation of NSCs was determined by immunofluorescence staining. The proliferation of NSCs was measured using the Cell Counting Kit-8 proliferation ***: Compared with the control group,CSF-QNYZD and AG490 significantly increased the number and expression of tubulin-positive cells, reduced the number and expression of GFAP-positive cells, and down-regulated the expression of p-STAT3. However, CSF-QNYZD also decreased the expression of SMAD-1 and ***: Enhanced neuronal differentiation may be associated with the down-regulation of glial differentiation instead of promoting proliferationin treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis.

关键词： Neural stem cells Glial fibrillary acidicprotein Cell differentiation Janus kinase 2 STAT3transcription factor Qingnaoyizhi decoction

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Huangqi Decoction,a compound Chinese herbal medicine,inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-βaxis

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Journal of Integrative medicine 2023年第1期21卷 47-61页

作者： Ben-sheng Dong Fu-qun Liu Wen-na Yang Xiao-dong Li Miao-juan Shi Mao-rong Li Xiu-li Yan Hui Zhang traditional Chinese medicine Epigenomics research Center Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Rheumatology and Immunology Nanjing Lishui District Hospital of Traditional Chinese MedicineNanjing 211299Jiangsu ProvinceChina Department of Rheumatology and Immunology Yangzhou University Medical CollegeYangzhou 225000Jiangsu ProvinceChina Department of Cardiovascular Physiology Faculty of MedicineKagawa UniversityKita-gunKagawa 761-0793Japan Department of Gastroenterology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China

Objective Huangqi Decoction(HQD),a classical traditional Chinese medicine formula,has been used as a valid treatment for alleviating liver fibrosis;however,the underlying molecular mechanism is still *** our previous studies showed that microRNA-663a(miR-663a)suppresses the proliferation and activation of hepatic stellate cells(HSCs)and the transforming growth factor-β/small mothers against decapentaplegic(TGF-β/Smad)pathway,whether long noncoding RNAs(lncRNAs)are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet *** present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic *** The expression levels of lnc-C18orf26-1,miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain *** were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering *** water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of *** in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated *** hybrid was used to predict the potential miR-663a binding sites on *** reporter assays further confirmed the interaction between miR-663a and the *** expression levels of collagen α-2(I)chain(COL1A2),α-smooth muscle actin(α-SMA)and TGF-β/Smad signaling pathway-related proteins were determined using western *** Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to *** of lnc-C18orf26-1 inhibited HSC proliferation and activation,downregulated TGF-β1-stimulatedα-SMA and COL1A2 expression,and inhibited the TGF-β1/Smad signaling *** suppressed the proliferation and activation of *** increased miR-663a expression and decreased lnc-C18orf26-1 expression in *** studies showed tha

关键词： Longnoncoding RNA-C18orf26-1 MicroRNA-663a Transforming growth factor-β Hepatic stellate cells Huangqi Decoction

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Characterization of a small-molecule inhibitor targeting NEMO/IKKβto suppress colorectal cancer growth

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1219-1231页

作者： Zhenlong Yu Jian Gao Xiaolei Zhang Yulin Peng Wenlong Wei Jianrong Xu Zhenwei Li Chao Wang Meirong Zhou Xiangge Tian Lei Feng Xiaokui Huo Min Liu Mingliang Ye De-an Guo Xiaochi Ma Pharmaceutical research Center Second Affiliated HospitalDalian Medical UniversityDalian 116000China College of Pharmacy College(Institute)of Integrative MedicineDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New Drug research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Shanghai research Center for Modernization of traditional Chinese medicine National Engineering Research Center for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Academy of Integrative medicine Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China Neurology Department Dalian University Affiliated Xinhua HospitalDalian 116021China

NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic ***,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO *** destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in *** addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβ*** study provides some new insights for the development of potent small-molecule PPI inhibitors.

关键词： IKKβ colorectal cancer

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