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| 1 | Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells显示文摘Background The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to self-renew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton’s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton’s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton’s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and β-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate. The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy (EM), and laser scanning confocal microscopy (LSCM) .The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results MSCs in the Wharton’s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease (GVHD)-related cells. Treatment with Salvia miltiorrhiza caused Wharton’s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia miltiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulinⅢ, neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharton’s Jelly. They were capable of differentiating into nerve-like cells using Salvia miltiorrhiza or β-mercaptoethanol. The induced MSCs not only underwent morphologic changes, but also expressed the neuron-related genes and neuronal cell markers. They may represent an alternative source of stem cells for central nervous system cell transplantation. | MA Lian FENG Xue-yong CUI Bing-lin Frieda Law JIANG Xue-wu YANG Li-ye XIE Qing-dong HUANG Tian-hua | 2005 | Chinese Medical Journal2005，，23： | 103 |
| 2 | Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression显示文摘Recently,increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease(AD)progression,yet the role of gut microbiota in AD pathogenesis remains obscure.Herein,we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression.Using AD mouse models,we discovered that,during AD progression,the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine,which stimulates the differentiation and proliferation of pro-inflammatory T helper 1(Thl)cells.The brain-infiltrated peripheral Th1 immune cells are associated with the Ml microglia aaivation,contributing to AD-associated neuroinflammation.Importantly,the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment(MCI)due to AD.Furthermore,GV-971,a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China,suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation,harnesses neuroinflammation and reverses the cognition impairment.Together,our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. | Xinyi Wang Guangqiang Sun Teng Feng Jing Zhang Xun Huang Tao Wang Zuoquan Xie Xingkun Chu Jun Yang Huan Wang Shuaishuai Chang Yanxue Gong Lingfei Ruan Guanqun Zhang Siyuan Yan Wen Lian Chen Du Dabing Yang Qingli Zhang Feifei Lin Jia Liu Haiyan Zhang Changrong Ge Shifu Xiao Jian Ding Meiyu Geng | 2019 | Cell Research2019，29，10： | 192 |
| 3 | Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21^(WAF1) expression and hepatic apoptosis显示文摘AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21WAF1gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21WAF1expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39(53.8%)cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3(87.5%,7/8)as compared with HCC(P<0.05).The expression of caspase 3 is correlated withHCC differentiation,72.2%(13/18)ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts(P<0.05).No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%(5/8)of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis(51.6%,P>0.05).Expression of caspase 3 alone did not affect the apoptosisindex(AI)of HCC.The AI was 7.12%o in caspase3-positive tumors(n=21),while in caspase 3-negative cases(n=18)6.59%0(P>0.05).Expression of caspase 3 clearly segregated withp21WAF1positive tumors as compared withp21WAF1-negative cases(16 of 23,69.6% versus5 of 16,31.3%)with statistical significance(P=0.017).In the cases with positive caspase 3and negative p21WAF1,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21WAF1and caspase 3(7.21‰ vs 6.98‰,P>0.05).CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21WAF1may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs. | Bao Hua Sun Jun Zhang Bao JǜWang Xi Ping Zhao You Kun Wang Zhi Qun Yu Dong Liang Yang Lian Jie Hao Department of Clinical Immunology,Tongji Hospital,Tongji Medical University,Wuhan 430030,Hubei Province,China | 2000 | World Journal of Gastroenterology2000，6，3： | 65 |
| 4 | The Genome of Dendrobium officinale Illuminates the Biology of the Important Traditional Chinese Orchid Herb显示文摘 | Liang Yan Xiao Wang Hui Liu Yang Tian Jinmin Lian Ruijuan Yang ShumeiHao Xuanjun Wang Shengchao Yang Qiye Li Shuai Qi Ling Kui Moses Okpekum Xiao Ma Jiajin Zhang Zhaoli Ding Guojie Zhang Wen Wang Yang Dong Jun Sheng | 2015 | Molecular Plant2015，8，6： | 64 |
| 5 | Get effective polyclonal antisera in one month显示文摘According to the traditional immunization procedure, after the first injection of the sample A (emulsion of aimed antigen and Freund's complete adjuvant) to immunize rabbit, successive injections of the sample B (emulsion of aimed antigen and Freund's incomplete adjuvant) were followed every 2-4 weeks. In general,high titer of the corresponding polyclonal antisera will be observed after 4-5 injections of sample B in 3-4months. This report presents a simply modified procedure that was able to stimulate the antisera formation in one month and achieve enough avidity to satisfy either Western blot or immunohistochemistry analysis.It just applied an additional injection of the sample A to the rabbit at the 3rd day after the primary immunization injection. You could gain the high titer of the antisera right after the first sample B injection in one month. This method has produced the desired results in three different recombinant antigens with different molecular weight (5.9 KD-55 KD) expressed from prokaryotic or eukaryotic cells. | YUAN XIN HU, Ju YUAN QUO, Lu SHEN, YAN CHEN, Zu CHUAN ZHANG, YONG LIAN ZHANGState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, | 2002 | Cell Research2002，12，2： | 45 |
| 6 | De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis显示文摘AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality. | Jiang-Shan Lian Lin-Yan Zeng Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang Liang Yu Jian-Hua Hu Ying-Feng Lu Ling Zheng Lan-Juan Li Yi-Da Yang | 2013 | World Journal of Gastroenterology2013，19，37： | 36 |
| 7 | Locking plate fixation combined with iliac crest bone autologous graft for proximal humerus comminuted fracture显示文摘 | Zhu Lian Liu Yueju Yang Zongyou Li Han Wang Juan Zhao Changping Chen Xiao Zhang Yingze | 2014 | Chinese Medical Journal2014，，9： | 40 |
| 8 | Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine显示文摘Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases. | Xizhan Xu Zezheng Gao Fuquan Yang Yingying Yang Liang Chen Lin Han Na Zhao Jiayue Xu Xinmiao Wang Yue Ma Lian Shu Xiaoxi Hu Na Lyu Yuanlong Pan Baoli Zhu Linhua Zhao Xiaolin Tong Jun Wang | 2020 | Genomics, Proteomics & Bioinformatics2020，18，6： | 29 |
| 9 | Phytochrome B Is Involved in Mediating Red Light-Induced Stomatal Opening in Arabidopsis thaliana显示文摘更高的植物的有气孔的毛孔为光合作用和蒸发启用气体的交换进并且从叶子。有气孔的开被蓝、红的灯导致。蓝导致光的有气孔的洞被蓝轻受体 phototropins (PHOT1 和 PHOT2 ) 和 cryptochromes (CRY1 和 CRY2 ) 调停,这被显示出。然而, phytochrome B (phyB ) 是否涉及有气孔的开的红轻规定,仍然保持大部分不清楚。这里,我们为 Arabidopsis (Arabidopsis thaliana ) 报导一个积极角色在红的规定的 phyB 导致光的有气孔的洞。phyB 异种 stomata 显示了减少的红轻回答,而 phyB-overexpressing 植物的 stomata 显示了过分敏感的回答到红光。另外, cry1 cry2 phyB , phot1 phot2 phyB ,和变异的植物更显示出的 cry1 phyA phyB 三元组的 stomata 在白色下面的植物点亮的单个或双的异种比那些减少了轻反应,暗示 phyB 在有 phyA 的音乐会行动,叫喊,并且在有气孔的开的轻规定的辐透。cop1 异种 cop1 异种开不比那些宽的 phyB 的 Stomata,和 pif3 pif4 异种的 stomata 开比那些宽野类型,和程序信息文件(phytochrome 交往因素) ,显示那 COP1 可以在调整有气孔的开 PHYB 下游地行动。而且,量的 RTPCR 分析证明分别地, MYB60 的表示在蓝、红的灯下面在 cry1 cry2 和 phyA phyB 异种被减少,但是在 CRY1-overexpressing 和 phyB-overexpressing 植物导致了。这些结果证明 phyB 和叫喊可能调整有气孔的开,至少部分地,由调整 MYB60 表示。 | Fang-Fang Wang Hong-Li Lian Chun-Ying Kang Hong-Quan Yang | 2010 | Molecular Plant2010，3，1： | 25 |
| 10 | Photoactivated CRY1 and phyB Interact Directly with AUX/IAA Proteins to Inhibit Auxin Signaling in Arabidopsis显示文摘光是在 Arabidopsis 通过蓝色和调停 cryptochrome 的 red/far-red 光光敏电阻器和调停 phytochrome 的小径禁止胚轴房间延伸的关键环境暗示。相反,作为枢轴的内长的植物激素,植物生长素通过 AUX/IAA 蛋白质(AUX/IAAs ) 的植物生长素受体 TIR1/AFBs-mediated 降级支持胚轴延伸。然而,位于发信号的光和植物生长素的对抗相互作用下面的分子的机制仍然保持不清楚。这里,我们报导光禁止由 cryptochrome 的蓝、红的轻依赖者的相互作用通过 AUX/IAAs 的稳定发信号的植物生长素 1 (CRY1 ) 并且有 AUX/IAAs 的 phytochrome B 分别地。有 AUX/IAAs 的 CRY1 的蓝被触发光的相互作用与 AUX/IAAs 禁止 TIR1 的协会,导致这些蛋白质的导致植物生长素的降级的压抑。我们的结果显示光敏电阻器下游地直接作为一样与植物生长素受体分享 AUX/IAAs 表明部件。我们建议由光敏电阻器和植物生长素受体的 AUX/IAA 蛋白质稳定性的那条对抗规定允许植物平衡光和植物生长素信号优化他们的生长。 | Feng Xu Shengbo He Jingyi Zhang Zhilei Mao Wenxiu Wang Ting Li Jie Hua Shasha Du Pengbo Xu Ling Li Hongli Lian Hong-Quan Yang | 2018 | Molecular Plant2018，11，4： | 24 |
| 11 | Construction, expression and characterization of the engineered antibody against tumor surface antigen, p185^(c-erbB-2)显示文摘The c-erbB-2 proto-oncogene encodes a 185kDa protein p185, which belongs to epidermal growth factorreceptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis forcertain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibitsproliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy. Inorder to overcome several drawbacks of murine MAb, we cloned its VH and VL genes and constructed thesingle-chain Fv (scFv) through a peptide linker. The recombinant scFvA21 was expressed in Escherichiacoli and purified by the affinity column. Subsequently it was characterized by ELISA, Western blot, cellimmunohistochemistry and FACS. All these assays showed the binding activity to extracellular domain(ECD) of p185. Based on those properties of scFvA21, we further constructed the scFv-Fc fusion moleculewith a homodimer form and the recombinant product was expressed in mammalian cells. In a series ofsubsequent analysis this fusion protein showed identical antigen binding site and activity with the parentantibody. These anti-p185 engineered antibodies have promised to be further modified as a tumor targetingdrugs, with a view of application in the diagnosis and treatment of human breast cancer. | LIAN SHENG CHENG, AI PING LIU, JIA HONG YANG, YAN QIU DONG, LIANG WEI LI, JING WANG, CHAO CHEN WANG, JING LIUSchool of Life Science, University of Science and Technology of China, Hefei 230027, China | 2003 | Cell Research2003，13，1： | 24 |
| 12 | Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B显示文摘AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir. | Hong-Yu Jia Feng Ding Jian-Yang Chen Jiang-Shan Lian Yi-Min Zhang Lin-Yan Zeng Dai-Rong Xiang Liang Yu Jian-Hua Hu Guo-Dong Yu Huan Cai Ying-Feng Lu Lin Zheng Lan-Juan Li Yi-Da Yang | 2015 | World Journal of Gastroenterology2015，21，12： | 22 |
| 13 | Red-Light-Dependent Interaction of phyB with SPA1 Promotes COP1-SPA1 Dissociation and Photomorphogenic Development in Arabidopsis显示文摘Arabidopsis phytochromes (phyA-phyE ) 是奉献给察觉到 red/far-red 光的光敏电阻器。Phytochromes 经由包含程序信息文件(PHYTOCHROME 交往因素) 和 COP1 (组成的 PHOTOMORPHOGENIC 1 ) 的抑制的快速的降级的一条发信号的小径在轻照耀之上支持 photomorphogenic 开发原子累积通过和程序信息文件和 COP1 的物理相互作用,分别地。phyA 和 phyB,二最好描绘的 phytochromes,分别地在 far-red 光和红光下面主要调整植物 photomorphogenesis。它被表明了那 SPA1 (PHYTOCHROME A 的 SUPPRESSOR 1 ) 与 COP1 联系支持 COP1 活动并且压制 photomorphogenesis。这里,我们报导在红光位于支持 phyB 的 photomorphogenesis 下面的机制包含在 red-light-activated phyB 和 SPA1 之间的直接物理、功能的相互作用。我们发现那 SPA1 PHYB 遗传上下游的行为镇压在红光的 photomorphogenesis。在酵母和 Arabidopsis 的蛋白质相互作用研究证明用光使敏化的 phyB 镇压有 COP1 的 SPA1 的协会,被调停,至少部分地,通过有 SPA1 的 phyB 的 red-light-dependent 相互作用。而且,我们证明 phyA 身体上以一种 Pfr-form-dependent 方式与 SPA1 交往,并且那 SPA1 PHYA 下游地行动在 far-red 光调整 photomorphogenesis。这研究提供怎么用光使敏化 phyB 的一个基因、生物化学的模型镇压通过和 SPA1 到的直接相互作用复杂的 COP1SPA1 的活动在红光支持 photomorphogenesis。 | Xue-Dan Lu Chuan-Miao Zhou Peng-Bo Xu Qian Luo Hong-Li Lian Hong-Quan Yang | 2015 | Molecular Plant2015，8，3： | 21 |
| 14 | Expression of insulin-like growth factor Ⅱ and its receptor in liver cells of chronic liver diseases显示文摘ExpressionofinsulinlikegrowthfactorⅡanditsreceptorinlivercelsofchronicliverdiseasesYANGDongHua1,XIUChong1,YANGBo1,GUJianR... | YANG Dong Hua 1, XIU Chong 1, YANG Bo 1, GU Jian Ren 2, QIAN Lian Fang 2 and QU Shu Ming 2 | 1997 | World Journal of Gastroenterology1997，3，2： | 21 |
| 15 | Preparation and activity of conjugate of monoclonal antibody HAb18 against hepatoma F( ab′ )_2 fragment and staphylococcal enterotoxin A显示文摘AIM To prepare the conjugate of staphylococcal enterotoxin A (SEA) protein which is a bacterial SAg and the F(ab')2 fragment of mAb HAbl8 against human hepatocellular carcinoma (HCC), and identify its activity in order to use SAg in the targeting therapy of HCC.METHODS MAb HAbl8 was extracted from the abdominal dropsy of Balb/ c mice, and was purified through chromatography column SP-40HR with Fast protein liquid chromatography (FPLC) system. The F(ab')2 fragment of mAb HAb18 was prepared by papainic digestion method. The conjugate of mAb HAb18 F(ab')2fragment and SEA was prepared with chemical conjugating reagent N-succinimidyl-3-( 2-pyridyldithio) propionate (SPDP) and purified through chromatography column Superose 12with FPLC system. The molecular mass and purity of each collected peak were identified with SDS-PAGE assay. The protein content was assayed by Lowry's method. The antibody activity of HAb18 F (ab')2 against HCC in the conjugate was identified by indirect immunocytochemical ABC method, and the activity of SEA in the conjugate to activate peripheral blood mononuclear cells (PBMC) was identified with MTT assay.RESULTS The lgG mAb HAb18 was extracted,and purified successfully. Immunocytochemical staining demonstrated that it reacted with most of HHCC cells of human HCC cell line. There were two peaks in the process of purification of the prepared HAb18 F(ab)2-SEA conjugate. SDS-PAGE assay demonstrated that the molecular mass of the first peak was about 130 ku, and the second peak was the mixture of about 45 ku and a little 100 ku proteins. The immunocytochemical staining was similar in HAb18 F (ab ')2-SEAconjugate and HAb18 F (ab ')2, i.e., thecytoplasm and/or cell membranes of most HHCC cells were positively stained. The MTT assay showed that the optical absorbance (A) value at 490 nm of HAb18 F (ab')2-SEA conjugate was 0.182 ± 0.012, that of negative control was 0.033± 0.009, and there was significant difference between them ( P < 0.05).CONCLUSION SPDP is a good proteinconjugating reagent and can be used in preparing protein conjugate. The conjugate of mAb HAb18F(ab')2 fragment and SEA protein was preparedsuccessfully in present study and can be used in the experimental study of HCC targeting therapy with the conjugate of SAg and anti-HCC mAbs or their fragments. | Lian Jun Yang Yan Fang Sui Zhi Nan Chen Department of Pathology, Fourth Military Medical University. Xi’an 710032, Shaanxi Province, China | 2001 | World Journal of Gastroenterology2001，7，2： | 20 |
| 16 | Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma显示文摘INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells . | Xiao Wei Li~1 Yan Qing Ding~1 Jun Jie Cai~1 Shao Qing Yang~2 Lian Bing An~3 Dong Fang Qiao~3 ~1Department of Pathology,Nanfang Hospital of the First Military Medical University,Guangzhou 510515,Guangdong Province,China ~2The Northern Hospital of PLA,Shenyang 110015,Liaoning Province,China ~3Department of Electronmicroscopy,First Military Medical University,Guangzhou 510515,Gangdong Province,ChinaDr.Xiao Wei Li graduated from the First Military Medical University with a MM degree in 1999.Physician in Charge of pathology,having 6 papers published. | 2001 | World Journal of Gastroenterology2001，7，3： | 19 |
| 17 | Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues: A Prospective Study显示文摘 | Jing Zhou Yue-Ying Liu Jiang-Shan Lian Li-Fang Pan Jian-Le Yang Jian-Rong Huang | 2017 | Chinese Medical Journal2017，，8： | 19 |
| 18 | Infection with novel coronavirus(SARS-CoV-2)causes pneumonia in Rhesus macaques显示文摘The 2019 novel coronavirus(SARS-CoV-2)outbreak is a major challenge for public health.SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases,with a mortality rate of^6.4%worldwide(based on World Health Organization daily situation report).However,the dynamics of viral infection,replication and shedding are poorly understood.Here,we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2.After intratracheal inoculation,the first peak of viral RNA was observed in oropharyngeal swabs one day post infection(1 d.p.i.),mainly from the input of the inoculation,while the second peak occurred at 5 d.p.i.,which reflected on-site replication in the respiratory tract.Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals,characterized by hyperemia and edema,and infiltration of monocytes and lymphocytes in alveoli.We also identified SARS-CoV-2 RNA in respiratory tract tissues,including trachea,bronchus and lung;and viruses were also re-isolated from oropharyngeal swabs,bronchus and lung,respectively.Furthermore,we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2.The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics. | Chao Shan Yan-Feng Yao Xing-Lou Yang Yi-Wu Zhou Ge Gao Yun Peng Lian Yang Xue Hu Jin Xiong Ren-Di Jiang Hua-Jun Zhang Xiao-Xiao Gao Cheng Peng Juan Min Ying Chen Hao-Rui Si Jia Wu Peng Zhou Yan-Yi Wang Hong-Ping Wei Wei Pang Zheng-Fei Hu Long-Bao Lv Yong-Tang Zheng Zheng-Li Shi Zhi-Ming Yuan | 2020 | Cell Research2020，30，8： | 19 |
| 19 | Collagen type Ⅱ suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction显示文摘Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previously considered to be only a structural component of the cartilage matrix,but recently,it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy.However,the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear.In our study,a Col2a1 p.Gly1170Ser mutant mouse model was constructed,and Col2a1 loss was demonstrated in homozygotes.Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein(BMP)-SMAD1 pathway.Upon interacting with COL2A1,integrinβ1(ITGB1),the major receptor for COL2A1,competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import.COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and,through ERK1/2-SMAD1 interaction,it further repressed SMAD1 activation,thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy.Moreover,COL2A1 expression was downregulated,while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage.Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression. | Chengjie Lian Xudong Wang Xianjian Qiu Zizhao Wu Bo Gao Lei Liu Guoyan Liang Hang Zhou Xiaoming Yang Yan Peng Anjing Liang Caixia Xu Dongsheng Huang Peiqiang Su | 2019 | Bone Research2019，7，1： | 17 |
| 20 | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway显示文摘Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin,which has shown various pharmacological activities including anti-inflammatory,antitumor,antioxidant,etc.Thus far,the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown.In this study,we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis(UC)as well as the underlying mechanisms.UC model was established in mice by administrating dextran sulfate sodium(DSS)in drinking water for 7 d.We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang,a traditional Chinese medicine decoction.UC mice were then treated with oroxindin(12.5,25,50 mg-kg^-1·d^-1,i.g.)for 10 d.We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue.Furthermore,oroxindin treatment significantly inhibited the generation of IL-13 and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasome formation and activation.In cultured macrophages,LPS induced NLRp3 inflammasome formation and caspase-1 activation,which were suppressed by oroxindin(12.5-50μM).In LPS-treated macrophages,oroxindin dose-dependently restored the expression of TXNIP protein,leading to suppressing TXNIP-dependent NF-κB activation.In conclusion,these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation,which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway.Hence,oroxindin has the potential of becoming an effective drug for treating UC. | Qi Liu Rui Zuo Kai Wang Fei-fei Nong Ya-jun Fu Shao-wei Huang Zeng-feng Pan Yi Zhang Xia Luo Xiang-liang Deng Xiao-xue Zhang Lian Zhou Yang Chen | 2020 | Acta Pharmacologica Sinica2020，41，6： | 15 |
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