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| 1 | Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection. | Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin | 2020 | Animal Models and Experimental Medicine2020，3，1： | 22 |
| 2 | Effect of endotoxin on fibronectin synthesis of rat primary cultured hepatocytes显示文摘EfectofendotoxinonfibronectinsynthesisofratprimaryculturedhepatocytesJIAJinBin,HANDeWu,XURuiLing,GAOFei,ZHAOLongFeng,ZHA... | JIA JinBin, HAN DeWu, XU RuiLing, GAO Fei, ZHAO LongFeng, ZHAO YuanChang, YAN JinPin and MA XueHuiKeywords liver cirrhosis endotoxins fibronectin/analysis liver/cytology cells, cultured lipopolysaccharide | 1998 | World Journal of Gastroenterology1998，4，4： | 14 |
| 3 | Molecular modeling on Zn(Ⅱ) binding modes of Alzheimer's amyloid β-peptide in insoluble aggregates and soluble complexes显示文摘Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain. | HAN Daxiong YANG Pin | 2004 | Science China Chemistry2004，47，2： | 7 |
| 4 | Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease显示文摘Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications. | Zhiqi Song Yajin Qu Yanfeng Xu Ling Zhang Li Zhou Yunlin Han Wenjie Zhao Pin Yu Yu Zhang Xianglei Li Chuan Qin | 2021 | Animal Models and Experimental Medicine2021，4，3： | 6 |
| 5 | Capecitabine with radiation is an effective adjuvant therapy in gastric cancers显示文摘AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers. | Chee Kian Tham Su Pin Choo Donald Yew Hee Poon Han Chong Toh Simon Yew Kuang Ong Sze Huey Tan Michael Lian Chek Wang Kian Fong Foo | 2010 | World Journal of Gastroenterology2010，16，29： | 6 |
| 6 | Minimally invasive video-assisted thyroidectomy for accidental papillary thyroid microcarcinoma: comparison with conventional open thyroidectomy with 5 years follow-up显示文摘背景最低限度地侵略的帮助录像的甲状腺切除( MIVAT )接受了增加注意因为这研究的恶意的甲状腺 diseases.The 目的是为乳突的甲状腺 microcarcinoma ( PTMC )把 MIVAT 的结果与常规开的甲状腺切除( CT )作比较 .Methods 31 个病人与 MIVAT 被对待并且 37 与 CT.Their 病理学的特征,外科的复杂并发症,5年的手术后的 thyroglobulin ( TG )和超声的结果是所有病人拿了的跟随的 up. | DI Jian-zhong ZHANG Hong-wei HAN Xiao-dong ZHANG Pin ZHENG Qi WANG Yu | 2011 | Chinese Medical Journal2011，，20： | 5 |
| 7 | Classification of traditional Chinese medicine constitution based on facial features in color images显示文摘Objective:To explore the possible correlation between traditional Chinese medicine(TCM)constitution and facial features in color images and to improve the accuracy of automated constitution classification.Methods:Color images were taken of 5150 individuals of different professions.Automated face detection and key point positioning were performed on the collected images,which were then transformed into a standard size.The relationship between facial features and TCM constitution based on the red,green,blue(RGB)pixel and the local binary pattern(LBP)texture features was explored.Results:The overall accuracy rate and robustness of TCM constitution classification based on RGB features were low.Classification results of the phlegm-dampness,damp-heat,blood stasis,and balance constitutions achieved high accuracy rates.Classification accuracy rate using the LBP texture feature was higher than that of the RGB feature,with the best accuracy observed for the balance constitution.Conclusion:Application of computer image acquisition and processing of facial features may serve as an adjunct to the TCM diagnostic method of inspection. | Jian Zhang Shujuan Hou Ji Wang Lingru Li Pin Li Junwen Han Haiqiang Yao Ranran Sun Ziqing Li Zhen Lei Qi Wang | 2016 | Journal of Traditional Chinese Medical Sciences2016，3，3： | 5 |
| 8 | Anorectal functional outcome after repeated transanal endoscopic microsurgery显示文摘AIM:To evaluate the status of anorectal function after repeated transanal endoscopic microsurgery(TEM).METHODS:Twenty-one patients undergoing subtotal colectomy with ileorectal anastomosis were included.There were more than 5 large(> 1 cm) polyps in the remaining rectum(range:6-20 cm from the anal edge).All patients,19 with villous adenomas and 2 with low-grade adenocarcinomas,underwent TEM with submucosal endoscopic excision at least twice between 2005 and 2011.Anorectal manometry and a questionnaire about incontinence were carried out at week 1 before operation,and at weeks 2 and 3 and 6 mo after the last operation.Anal resting pressure,maximum squeeze pressure,maximum tolerable volume(MTV) and rectoanal inhibitory reflexes(RAIR) were recorded.The integrity and thickness of the internal anal sphincter(IAS) and external anal sphincter(EAS) were also evaluated by endoanal ultrasonography.We determined the physical and mental health status with SF-36 score to assess the effect of multiple TEM on patient quality of life(QoL).RESULTS:All patients answered the questionnaire.Apart from negative RAIR in 4 patients,all of the anorectal manometric values in the 21 patients were normal before operation.Mean anal resting pressure decreased from 38 ± 5 mmHg to 19 ± 3 mmHg(38 ± 5 mmHg vs 19 ± 3 mmHg,P = 0.000) and MTV from 165 ± 19 mL to 60 ± 11 mL(165 ± 19 mL vs 60 ± 11 mL,P = 0.000) at month 3 after surgery.Anal resting pressure and MTV were 37 ± 5 mmHg(38 ± 5 mmHg vs 37 ± 5 mmHg,P = 0.057) and 159 ± 19 mL(165 ± 19 mL vs 159 ± 19 mL,P = 0.071),respectively,at month 6 after TEM.Maximal squeeze pressure decreased from 171 ± 19 mmHg to 62 ± 12 mmHg(171 ± 19 mmHg vs 62 ± 12 mmHg,P = 0.000) at week 2 after operation,and returned to normal values by postoperative month 3(171 ± 19 vs 166 ± 18,P = 0.051).RAIR were absent in 4 patients preoperatively and in 12(2 = 4.947,P = 0.026) patients at month 3 after surgery.RAIR was absent only in 5 patients at postoperative month 6(2 = 0.141,P = 0.707).Endosonography demonstrated that IAS disruption occurred in 8 patients,and 6 patients had temporary incontinence to flatus that was normalized by postoperative month 3.IAS thickness decreased from 1.9 ± 0.6 mm preoperatively to 1.3 ± 0.4 mm(1.9 ± 0.6 mm vs 1.3 ± 0.4 mm,P = 0.000) at postoperative month 3 and increased to 1.8 ± 0.5 mm(1.9 ± 0.6 mm vs 1.8 ± 0.5 mm,P = 0.239) at postoperative month 6.EAS thickness decreased from 3.7 ± 0.6 mm preoperatively to 3.5 ± 0.3 mm(3.7 ± 0.6 mm vs 3.5 ± 0.3 mm,P = 0.510) at month 3 and then increased to 3.6 ± 0.4 mm(3.7 ± 0.6 mm vs 3.6 ± 0.4 mm,P = 0.123) at month 6 after operation.Most patients had frequent stools per day and relatively high Wexner scores in a short time period.While actual fecal incontinence was exceptional,episodes of soiling were reported by 3 patients.With regard to the QoL,the physical and mental health status scores(SF-36) were 56.1 and 46.2(50 in the general population),respectively.CONCLUSION:The anorectal function after repeated TEM is preserved.Multiple TEM procedures are useful for resection of multi-polyps in the remaining rectum. | Hong-Wei Zhang Xiao-Dong Han Yu Wang Pin Zhang Zhi-Ming Jin | 2012 | World Journal of Gastroenterology2012，18，40： | 5 |
| 9 | Studies on bio-antioxidants——Ⅱ.An ESR study on the antioxidant efficiency of ascorbyl palmitate in micelles显示文摘The kinetics for the reaction of ascorbyl palmitate and 4-hydroxy-TEMPO,4-methoxy-TEMPO or 4-hexanoyloxy-TEMPO in CTAB and SDS micelles was studied by ESR spectroscopy.It was found that the behavior of ascorbyl palmitate is remarkably different from ascorbic acid in theirantioxidant activity in micelles.The predominant factors governing the activity in micelles involvethe lipophilicity of the antioxidant and the oxidant,the charge type of the substrates and the concentra-tion of the surfactant.As high as 2×10~4 fold rate variation was observed by changing the lipophilicityof the antioxidant and the microenvironment of the reaction medium. | LIU,Zhong-Li HAN,Zheng-Xu CHENG,Pin WU,Lung-Min LIU,You-Cheng National Laboratory on Applied Organic Chemistry and Department of Chemistry,Lanzhou University,Lanzhou,730000 | 1991 | Chinese Journal of Chemistry1991，9，2： | 4 |
| 10 | Dose-dense paclitaxel plus carboplatin vs.epirubicin and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer显示文摘Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk. | Qing Li Jiani Wang Yuxin Mu Tongtong Zhang Ying Han Jiayu Wang Qiao Li Yang Luo Fei Ma Ying Fan Pin Zhang Binghe Xulj | 2020 | Chinese Journal of Cancer Research2020，32，4： | 4 |
| 11 | Molecular modeling of the inhibitory mechanism of copper(II) on aggregation of amyloidβ-peptide显示文摘Aggregation of amyloid ?-peptide (A?) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory ef-fect on the Zn(II)-induced aggregation, which occurs significantly even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing A? from aggregating. The possible mechanism of the inhibitory effect of Cu(II) is in-vestigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of A?. Specially, [Cu-H13(Np)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(Np)-Y10(OH)] complex with quasi-helix conformations may prefer soluble forms in solution. In addition, hydro-gen-bond interactions may be the main driving force for A? aggregation. All the results will pro-vide helpful clues for an improved understanding of the role of Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy. | JIAO Yong HAN Daxiong YANG Pin | 2005 | Science China Chemistry2005，48，6： | 4 |
| 12 | DITERPENOIDS FROM RABDOSIA SCULPONEATA显示文摘Five ent-6,7-seco-karuene diterpenoids-enmein,epinodosin,sculponeatin A,C,D,were isolated from thedried leaves of Rabdosia sculponeata One of the compounds,named sculponeatin D,was previously unreported.Itsstructre was elucidated by the spectral data including 2D COSY,1H-13C correlation,2D NOESY spectroscopy. | Rong Pin ZHANG Hong Jie ZHANG Yu Lin ZHEN Han Dong SUN The Laboratory of Phytohemistry,Kunming Institute of Botany,Academia Sinica,Kunming,650204 Yunan Traditional Chinese Medical College,Kunming | 1991 | Chinese Chemical Letters1991，2，4： | 3 |
| 13 | Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice显示文摘Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Copyococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients. | Yuqiu Han Xiangyang Jiang Qi Ling Li Wu Pin Wu Ruiqi Tang Xiaowei Xu Meifang Yang Lijiang Zhang Weiwei Zhu Baohong Wang Lanjuan Li | 2019 | Frontiers of Medicine2019，13，4： | 3 |
| 14 | Two New Iridoid Glucosides from Clerodendrum serratum显示文摘Two new iridoid glucosides, serratoside A and serratoside B, were isolated from the aerial parts of Clerodendrum serratum var. amplexifolium Moldenke. Their structures were elucidated by spectral and chemical methods. | Hui YANG Bei JIANG Zhi NA Yun Pin GUO Han Dong SUN | 2000 | Chinese Chemical Letters2000，11，3： | 2 |
| 15 | Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many countries.However,the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown.Here,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune systems.The viral protein partially co-localized with activated Mac-2+macrophages throughout the body.Moreover,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal COVID-19.Particularly,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune dysregulation.Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation.Melatonin,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted medicine.Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers. | Zhiqi Song Linlin Bao Wei Deng Jiangning Liu Erjun Ren Qi Lv Mingya Liu Feifei Qi Ting Chen Ran Deng Fengdi Li Yunpeng Liu Qiang Wei Hong Gao Pin Yu Yunlin Han Wenjie Zhao Junjun Zheng Xujian Liang Fuhe Yang Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 2 |
| 16 | γδT17 Cells Promote the Accumulation and Expansion of Myeloid-Derived Suppressor Cells in Human Colorectal Cancer显示文摘 | Pin Wu Dang Wu Chao Ni Jun Ye Wuzhen Chen Guoming Hu Zhen Wang Changrong Wang Zhigang Zhang Wenjie Xia Zhigang Chen Ke Wang Tao Zhang Jinghong Xu Yuehua Han Ting Zhang Xianguo Wu Jianwei Wang Weihua Gong Shu Zheng Fuming Qiu Jun Yan Jian Huang | 2014 | Immunity2014，，5： | 2 |
| 17 | SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration显示文摘SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals.However,it remains undear whether and how SARS-CoV-2 crosses the blood-brain barrier(BBB).Herein,SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space,as well as in brain microvascular endothelial cells(BMECs)in the infected K18-hACE2 transgenic mice.Moreover,the permeability of the infected vessel was in creased.Furthermore,disin tegrity of BBB was discovered in the infected hamsters by administration of Evans blue.Interestingly,the expression of claudin5,ZO-1,occludin and the ultrastructure of tight junctions(TJs)showed unchanged,whereas,the basement membrane was disrupted in the infected animals.Using an in vitro BBB model that comprises primary BMECs with astrocytes,SARS-CoV-2 was found to infect and cross through the BMECs.Consistent with in vivo experiments,the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs.Besides,inflammatory responses including vasculitis,glial activation,and upregulated inflammatory factors occurred after SARS-CoV-2 infection.Overall,our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs. | Ling Zhang Li Zhou Linlin Bao Jiangning Liu Hua Zhu Qi Lv Ruixue Liu Wei Chen Wei Tong Qiang Wei Yanfeng Xu Wei Deng-Hong Gao Jing Xue Zhiqi Song Pin Yu Yunlin Han Yu Zhang Xiuping Sun Xuan Yu Chuan Qin | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 2 |
| 18 | Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma显示文摘Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum,bladder,breast,head and neck,and testicular germ cells.The aim of this study was to examine whether global hypomethylation in blood leukocyte DNA is associated with the risk of hepatocellular carcinoma (HCC).A total of 315 HCC cases and 356 age-,sex-and HBsAg status-matched controls were included.Global methylation in blood leukocyte DNA was estimated by analyzing long interspersed element-1 (LINE-1) repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing.We observed that the median methylation level in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower than that in controls (79.5% 5mC) (P=0.004,Wilcoxon rank-sum test).The odds ratios (ORs) of HCC for individuals in the third,second,and first (lowest) quartiles of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7-1.8),1.4 (95% CI 0.8-2.2),and 2.6 (95% CI 1.7-4.1) (P for trend <0.001),respectively,compared to individuals in the fourth (highest) quartile.A 1.9-fold (95% CI 1.4-2.6) increased risk of HCC was observed among individuals with LINE-1 methylation below the median compared to individuals with higher (>median) LINE-1 methylation.Our results demonstrate for the first time that individuals with global hypomethylation measured in LINE-1 repeats in blood leukocyte DNA have an increased risk for HCC.Our data provide the evidence that global hypomethylation detected in the easily obtainable DNA source of blood leukocytes may help identify individuals at risk of HCC. | Jian-zhong DI Xiao-dong HAN Wen-ye GU Yu WANG Qi ZHENG Pin ZHANG Hui-min WU Zhong-zheng ZHU | 2011 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2011，12，10： | 2 |
| 19 | A novel strategy to derive iPS cells from porcine fibroblasts显示文摘Induced pluripotent stem (iPS) cell technology demonstrates that somatic cells can be reprogrammed to a pluripotent state by over-expressing four reprogramming factors.This technology has created an interest in deriving iPS cells from domesticated animals such as pigs,sheep and cattle.Moloney murine leukemia retrovirus vectors have been widely used to generate and study mouse iPS cells.However,this retrovirus system infects only mouse and rat cells,which limits its use in establishing iPS cells from other mammals.In our study,we demonstrate a novel retrovirus strategy to efficiently generate porcine iPS cells from embryonic fibroblasts.We transfected four human reprogramming factors (Oct4,Sox2,Klf4 and Myc) into fibroblasts in one step by using a VSV-G envelope-coated pantropic retrovirus that was easily packaged by GP2-293 cells.We established six embryonic stem (ES)-like cell lines in human ES cell medium supplemented with bFGF.Colonies showed a similar morphology to human ES cells with a high nuclei-cytoplasm ratio and phase-bright flat colonies.Porcine iPS cells could form embryoid bodies in vitro and differentiate into the three germ layers in vivo by forming teratomas in immunodeficient mice. | RUAN WeiMin HAN JianYong LI Pin CAO SuYing AN Yang LIM Bing LI Ning | 2011 | Science China(Life Sciences)2011，54，6： | 2 |
| 20 | 显示文摘 | YANG PIN HAN DA-XIONG XIONG ZHEN-HAI | 2001 | J Mol Struc (THEOCHEM)2001，540，： | 1 |
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