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| 1 | Gene expression signatures for phlegm-dampness constitution of Chinese Medicine显示文摘Dear Editor,The term'individualized medicine'was first used in Biochemistry Individuality in 1956 by Williams(Williams et al.,1956).With the emergence of the post-genome era in the21st century,individualized precision medicine has attracted increasing attention.In traditional Chinese medicine(TCM),there is also concept of individualized medicine,which is known as the Chinese constitutional theory,proposed in the1970s(Wang,2012).According to this theory,the | Lingru Li Juan Feng Haiqiang Yao Lan Xie Yu Chen Lingling Yang Shujuan Hou Shipeng Zhao Ranran Sun Yanling Wu Tongtong Bai Yingshuai Li Ruoxi Yu Ji Wang Qi Wang | 2017 | Science China(Life Sciences)2017，60，1： | 13 |
| 2 | Expression profiling-based clustering of healthy subjects recapitulates classifications defined by clinical observation in Chinese medicine显示文摘Differences between healthy subjects and associated disease risks are of substantial interest in clinical medicine. Based on clinical presentations, Traditional Chinese Medicine(TCM) classifies healthy people into nine constitutions: Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat, Blood stasis,Qi stagnation, and Inherited special constitutions. In particular, Yang and Yin deficiency constitutions exhibit cold and heat aversion, respectively. However, the intrinsic molecular characteristics of unbalanced phenotypes remain unclear. To determine whether gene expression-based clustering can recapitulate TCM-based classification, peripheral blood mononuclear cells(PBMCs) were collected from Chinese Han individuals with Yang/Yin deficiency(n ? 12 each) and Balanced(n ? 8) constitutions, and global gene expression profiles were determined using the Affymetrix HG-U133 A Plus 2.0 array. Notably,we found that gene expression-based classifications reflected distinct TCM-based subtypes. Consistent with the clinical observation that subjects with Yang deficiency tend toward obesity, series-clustering analysis detected several key lipid metabolic genes(diacylglycerol acyltransferase(DGAT2), acyl-Co A synthetase(ACSL1), and ATP-binding cassette subfamily A member 1(ABCA1)) to be down-and upregulated in Yin and Yang deficiency constitutions, respectively. Our findings suggest that Yin/Yang deficiency and Balanced constitutions are unique entities in their m RNA expression profiles. Moreover,the distinct physical and clinical characteristics of each unbalanced constitution can be explained, in part,by specific gene expression signatures. | Ruoxi Yu Dan Liu Yin Yang Yuanyuan Han Lingru Li Luyu Zheng Ji wang Yan Zhang Yingshuai Li Qian-Fei Wang Qi wang | 2017 | Journal of Genetics and Genomics2017，44，4： | 9 |
| 3 | A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform显示文摘The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was chosen as the model drug. BN –NLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH-and thermo-sensitive hydrogel composed of carboxymethyl chitosan(CMCS) and poloxamer 407(F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin(GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH-and thermo-sensitive. The results of in vitro release suggested BN –NLC gel can prolong the release of baicalin comparing with BN eye drops and BN –NLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient(Papp) of BN –NLC gel was much higher(4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BN –NLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLCbased hydrogel has a promising potential for application in ocular drug delivery. | Yibin Yu Ruoxi Feng Jinyu Li Yuanyuan Wang Yiming Song Guoxin Tan Dandan Liu Wei Liu Xinggang Yang Hao Pan Sanming Li | 2019 | Asian Journal of Pharmaceutical Sciences2019，14，4： | 3 |
| 4 | Safety,tolerability,and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer:An open-label,dose-escalation,phase I study显示文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer. | Ruoxi Hong Wen Xia Liye Wang Kaping Lee Qianyi Lu Kuikui Jiang Shengfeng Li Jinquan Yu Jin Wei Weijia Tang Danyang Zhou Xin An Jiajia Huang Cong Xue Xiwen Bi Yanxia Shi Zhongyu Yuan Fei Xu Shusen Wang | 2021 | Cancer Communications2021，41，2： | 2 |
| 5 | Consistency between traditional Chinese medicine constitution-based classification and genetic classification显示文摘Background:We studied the consistency between two classification systems for categorizing patients:traditional Chinese medicine(TCM)constitution-based methods,versus genetic clustering.Genetic classification in constitutional identification was also evaluated.Methods:A TCM physician evaluated the constitution of each patient,according to four examinations(inspection,auscultation-olfaction,interrogation,and palpation).Those who met the criteria for Yang-deficient,Yin-deficient,and balanced constitutions were enrolled in the study.Peripheral blood samples were obtained from the participants,and peripheral blood mononuclear cells were separated from the samples within 2 hours.Total RNA extraction from the white blood cells was performed;and an Affymetrix HG-U133 Plus2.0 array was used to determine the peripheral blood gene expression profiles.The samples were classified using a support vector machine genetic classifier,and the“leave-one-out”method was used for validation.Results:The global gene expression profiles of 32 samples were grouped into three categories,and the samples in each of the gene categories corresponded with the three constitution categories.The three constitution types were distinguished using the genetic classifier with 165 genes.The accuracy of the prediction classification was greater than 95%using mathematical method.Conclusions:Participants with Yin-deficient,Yang-deficient,and balanced constitutions have varying physical characteristics and gene expression patterns.Additionally,the results from TCM constitution classification matched those obtained by genetic classification.Finally,our preliminary gene classifier distinguishes among Yin-deficient,Yang-deficient,and balanced constitutions,and provides a methodological basis for identifying the different constitutions. | Ruoxi Yu Xiaohong Zhao Lingru Li Cheng Ni Yin Yang Yuanyuan Han Ji Wang Yan Zhang Qi Wang | 2015 | Journal of Traditional Chinese Medical Sciences2015，2，4： | 2 |
| 6 | Hypothalamic paraventricular nucleus neurons activated by estrogen GPER1 receptors promote anti-inflammation effects in the early stage of colitis显示文摘The hypothalamus-pituitary-adrenal(HPA)axis is known to mediate gut-brain interaction,and the pathological inflammatory process in the intestine can induce HPA axis involved'fight or flight response to suppress or facilitate intestinal inflammation.Hypothalamic paraventricular nucleus(PVN)neurons are responsible for controlling the HPA axis activity,but their exact role in modulating intestinal inflammation remains unclear.In this study,we used the dextran sulfate sodium(DSS)-induced mice colitis model,gene editing,and RNA interference to determine the effects of PVN neurons on intestinal inflammation.We found that at the early stage(third day)after DSS treatment,there was a mild inflammation in the colorectal area and an increased neuron activatio n in the PVN but not in the adjace nt area.At the same time,~80% of activated PVN n eurons also expressed novel estrogen GPER1 receptor.The colitis noticeably worsened in GPER1-knockout mice and local PVN GPER1-knockdown mice.These results indicated that PVN GPER1 positive neurons potentially have a protective function during the early stages of DSS-induced colitis,and this may be a mechanism by which the central nervous system attempts to suppress intestinal inflammation to achieve self-protection. | Tao Jiang Ruoxi Wang Wen Yin Yuxi Zhou Dexu Kong Saihong Xu Po Gao Weifeng Yu Yingfu Jiao Daxiang Wen | 2019 | Acta Biochimica et Biophysica Sinica2019，51，12： | 1 |
| 7 | Urotensin Ⅱ receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCI4-induced cirrhotic rats显示文摘Increased serum urotensin Ⅱ(UⅡ) levels in human cirrhotic populations have been recently shown,but the long-term effects of UⅡ receptor antagonist on the cirrhosis have not been investigated.To investigate the therapeutic effects of urotensin Ⅱ receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCI4)- induced cirrhosis,the hepatic and systemic hemodynamics,liver fibrosis,the metalloproteinase-13 (MMP-13)/ tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio,hepatic Rho-kinase activity,and the endothelial nitric oxide synthase (eNOS) activity are measured in CCI4-cirrhotic rats treated with palosuran or vehicle for 4 weeks.Primary hepatic stellate cells (HSCs) are used to investigate the changes in UⅡ/UT expression and the in vitro effect of palosuran.Compared with the vehicle-treated cirrhotic rats,treatment with palosuran can reduce the portal pressure (PP),decrease the risk of liver fibrosis and the level of a smooth muscle actin,collagen-l (COL-I),and transforming growth factor β expression.However,treatment with palosuran can increase MMP-13/TIMP-1,pvasodilator- stimulated phosphoprotein (p-VASP),and p-eNOS expression.Moreover,in vitro UⅡ/UT mRNA expression increases during HSC activation.MMP-13/TIMP-1,COL-I,and p-VASP are inhibited after palosuran treatment Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis,which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation. | Ruoxi Zhang Jing Chen Diangang Liu Yu Wang | 2019 | Frontiers of Medicine2019，13，3： | 1 |
| 8 | Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer显示文摘Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf RNA.Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer. | Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei Liu Hexiang Deng Shuang Peng Xiang Zhou | 2024 | National Science Review2024，11，1： | 0 |
| 9 | Reliability of online near-infrared spectroscopy analysis of the ex-traction process of Huatan Qushi decoction for phlegm-dampness constitution显示文摘OBJECTIVE: To establish a quantitative model for the online analysis of hesperidin content in the extraction process of Huatan Qushi decoction for individuals with phlegm-dampness constitution by using near-infrared(NIR) spectroscopy and partial least squares(PLS) methods.METHODS: The reference content of hesperidin, an effective ingredient of Huatan Qushi decoction,was determined using high-performance liquid chromatography(HPLC). The modeling band was selected using synergy interval PLS(Si PLS) algorithms, and a PLS model demonstrating the relationship between NIR predictive values and HPLC reference values was established. The optimal modeling route was selected through global optimization of process trace parameters.RESULTS: The root mean square error of cross-validation was 9.8410. The coefficients of determination of the calibration set and prediction set were0.9860(R2 cal) and 0.9458(R_(cal)~2), respectively. The residual predictive deviation was 3.0115. The parameters demonstrated high predictive capability and reliability. The band was selected via the Si PLS method. There were seven latent variables.CONCLUSION: This study provides a favorable comprehensive evaluation method for variable selection and quality control of the Traditional Chinese Medicine extraction process. | Zhao Shipeng Zheng Yanfei Li Pin Liang Xue Bao Lei Chen Yu Yu Ruoxi Sun Ranran Li Lingru Wang Qi | 2017 | Journal of Traditional Chinese Medicine2017，37，6： | 0 |
| 10 | Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution显示文摘OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study respectively.The clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome analysis.The differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were conducted.RESULTS:There were no statistical differences found in the baseline data.For vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial dysfunction.There are 66 differentially expressed serum proteins between the two groups.apolipoprotein A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with RHI.CONCLUSION:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese group.Thus,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD. | ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru | 2024 | Journal of Traditional Chinese Medicine2024，44，1： | 0 |
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