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| 1 | Effects of Acupuncture on Alzheimer’s Disease: Evidence from Neuroimaging Studies显示文摘As the worldwide population ages, the prevalence of Alzheimer's disease (AD) increases. However, the results of promising medications have been unsatisfactory. Chinese acupuncture has a long history of treating dementia, but lack of evidence from well-designed randomized controlled trials that validate its efficacy and safety, as well as its lack of clear underlying mechanisms, contribute to its limited application in clinical practice. In recent years, brain imaging technologies, such as functional magnetic resonance imaging and positron emission tomography, have been used to assess brain responses to acupuncture in a dynamic, visual, and objective way. These techniques are frequently used to explore neurological mechanisms of responses to acupuncture in AD and provide neuroimaging evidence as well as starting points to elucidate the possible mechanisms. This review summarizes the existing brain imaging evidence that explains the effects of acupuncture for AD and analyzes brain responses to acupuncture at cognitive-related acupoints [Baihui (GV 20), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), and Taixi (KI 3)] from perspectives of acupoint specificity and acupoint combinations. Key issues and directions to consider in future studies are also put forward. This review should deepen our understanding of how brain imaging studies can be used to explore the underlying mechanisms of acupuncture in AD. | YU Chao-chao MA Chao-yang WANG Hua KONG Li-hong ZHAO Yan SHEN Feng WU Miao | 2019 | Chinese Journal of Integrative Medicine2019，25，8： | 18 |
| 2 | Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis显示文摘AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs.METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs. | Srinivas R Puli Nikhil Kalva Matthew L Bechtold Smitha R Pamulaparthy Micheal D Cashman Norman C Estes Richard H Pearl Fritz-Henry Volmar Sonu Dillon Michael F Shekleton David Forcione | 2013 | World Journal of Gastroenterology2013，19，23： | 14 |
| 3 | A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling显示文摘The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells,which are profoundly moulded by cancer cells.An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs.Here,we profile 233,591 single cells from patients with lung,colorectal,ovary and breast cancer(n=36)and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies.We identify 68 stromal cell populations,of which 46 are shared between cancer types and 22 are unique.We also characterise each population phenotypically by highlighting its marker genes,transcription factors,metabolic activities and tissue-specific expression differences.Resident cell types are characterised by substantial tissue specificity,while tumor-infiltrating cell types are largely shared across cancer types.Finally,by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naive CD4+T-cell phenotype predictive of response to checkpoint immunotherapy,we illustrate how it can serve as a guide to interpret scRNA-seq data.In conclusion,by providing a comprehensive blueprint through an interactive web server,we generate the first panoramic view on the shared complexity of stromal cells in different cancers. | Junbin Qian Siel Olbrecht Bram Boeckx Hanne Vos Damya Laoui Emre Etlioglu Els Wauters Valentina Pomella Sara Verbandt Pieter Busschaert Ayse Bassez Amelie Franken Marlies Vanden Bempt Jieyi Xiong Birgit Weynand Yannick van Herck Asier Antoranz Francesca Maria Bosisio Bernard Thienpont Giuseppe Floris Ignace Vergote Ann Smeets Sabine Tejpar Diether Lambrechts | 2020 | Cell Research2020，30，9： | 11 |
| 4 | Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response显示文摘Personalized immunotherapy targeting tumor-specific antigens(TSAs)could generate efficient and safe antitumor immune response without damaging normal tissues.Although neoantigen vaccines have shown therapeutic effect in clinic trials,precise prediction of neoantigens from tumor mutations is still challenging.The host antitumor immune response selects and activates T cells recognizing tumor antigens.Hence,T cells engineered with T-cell receptors(TCRs)from these naturally occurring tumor antigen-specific T(Tas)cells in a patient will target personal TSAs in his/her tumor.To establish such a personalized TCR-T cell therapy,we comprehensively characterized T cells in tumor and its adjacent tissues by single-cell mRNA sequencing(scRNA-seq),TCR sequencing(TCR-seq)and in vitro neoantigen stimulation.Compared to bystander T cells circulating among tissues,Tas cells were characterized by tumor enrichment,tumor-specific clonal expansion and neoantigen specificity.We found that CXCL13 is a unique marker for both CD4^(+)and CD8^(+)Tas cells.Importantly,TCR-T cells expressing TCRs from Tas cells showed significant therapeutic effects on autologous patient-derived xenograft(PDX)tumors.Intratumoral Tas cell levels measured by CXCL13 expression precisely predicted the response to immune checkpoint blockade,indicating a critical role of Tas cells in the antitumor immunity.We further identified CD200 and ENTPD1 as surface markers for CD4^(^(+))and CD8^(^(+))Tas cells respectively,which enabled the isolation of Tas cells from tumor by Fluorescence Activating Cell Sorter(FACS)sorting.Overall,our results suggest that TCR-T cells engineered with Tas TCRs are a promising agent for personalized immunotherapy,and intratumoral Tas cell levels determine the response to immunotherapy. | Jingjing He Xinxin Xiong Han Yang Dandan Li Xuefei Liu Shuo Li Shuangye Liao Siyu Chen Xizhi Wen Kuai Yu Lingyi Fu Xingjun Dong Kaiyu Zhu Xiaojun Xia Tiebang Kang Chaochao Bian Xiang Li Haiping Liu Peirong Ding Xiaoshi Zhang Zhenjiang Liu Wende Li Zhixiang Zuo Penghui Zhou | 2022 | Cell Research2022，32，6： | 10 |
| 5 | Detection of Salmonella and several common Salmonella serotypes in food by loop-mediated isothermal amplification method显示文摘Salmonella Choleraesuis,S.Enteritidis and S.Typhimurium are the main pathogens that contaminate animal products and cause human Salmonella food poisoning.To establish the loop-mediated isothermal amplification(LAMP)method for the rapid detection of Salmonella and 3 common Salmonella serotypes,inner and outer primer sets targeting Salmonella invE gene and 3 serotype-specific genes fliC,lygD and STM4495 were designed.The LAMP reaction conditions were optimized.The specificity of LAMP primers was identified by testing 10 different bacterial strains including S.Choleraesuis,S.Enteritidis and S.Typhimurium.Take S.Choleraesuis as example,the detection limit of LAMP assay was 1.33×10^1 CFU/mL for bacteria culture and 2.0×10^1 CFU/mL for simulated pork sample.The results show that LAMP is a rapid,sensitive and specific method for Salmonella detection and can be used for the rapid detection of Salmonella in food. | Zhongqiang Chen Ke Zhang Huan Yin Qi Li Lan Wang Zhiguo Liu | 2015 | Food Science and Human Wellness2015，4，2： | 8 |
| 6 | Three Novel Real-Time RT-PCR Assays for Detection of COVID-19 Virus显示文摘What is already known on this topic?A novel human coronavirus,known as SARS-CoV-2 or 2019-nCoV,is the causative agent of the coronavirus disease 2019(COVID-19).We have released the primers and probes of real-time reverse transcription polymerase chain reaction(rRT-PCR)assays for the laboratory detection of COVID-19 infection.What is added by this report?Here we provide detailed technical data and evaluate the performance of three novel rRT-PCR assays targeting the ORF1ab,N,and E genes for detection of COVID-19 infection.The application of rRT-PCR assays among four types of specimens(alveolar lavage,sputum,throat swabs,and stool)from patients with COVID-19 indicated that the mean viral loads detected in sputum were higher than other specimens.What are the implications for public health practice?These rRT-PCR assays reported here could be used for laboratory diagnosis of COVID-19 infection with high sensitivity,specificity,and applicability.Sputum rather than throat swabs and stool should be a priority for specimen collection for laboratory detection of COVID-19. | Peihua Niu Roujian Lu Li Zhao Huijuan Wang Baoying Huang Fei Ye Wenling Wang Wenjie Tan | 2020 | China CDC weekly2020，2，25： | 8 |
| 7 | Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification显示文摘AIM:To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease(NAFLD).METHODS:Cross-sectional study of subjects from the general population,a subgroup from the First Israeli National Health Survey,without excessive alcohol consumption or viral hepatitis.All subjects underwent anthropometric measurements and fasting blood tests.Evaluation of liver fat was performed using four noninvasive methods:the SteatoTest;the fatty liver index(FLI);regular abdominal ultrasound(AUS);and the hepatorenal ultrasound index(HRI).Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods:the HRI,the ratio between the median brightness level of the liver and right kidney cortex;and the SteatoTest,a biochemical surrogate marker of liver steatosis.The FLI is calculated by an algorithm based on triglycerides,body mass index,γ-glutamyl-transpeptidase and waist circumference,that has been validated only vs AUS.FLI < 30 rules out and FLI ≥ 60 rules in fatty liver.RESULTS:Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests.The prevalence rate of NAFLD was 31.1% according to AUS.The FLI was very strongly correlated with SteatoTest(r = 0.91,P < 0.001) and to a lesser but significant degree with HRI(r = 0.55,P < 0.001).HRI and SteatoTest were significantly correlated(r = 0.52,P < 0.001).The κ between diagnosis of fatty liver by SteatoTest(≥ S2) and by FLI(≥ 60) was 0.74,which represented good agreement.The sensitivity of FLI vs SteatoTest was 85.5%,specificity 92.6%,positive predictive value(PPV) 74.7%,and negative predictive value(NPV) 96.1%.Most subjects(84.2%) with FLI < 60 had S0 and none had S3-S4.The κ between diagnosis of fatty liver by HRI(≥ 1.5) and by FLI(≥ 60) was 0.43,which represented only moderate agreement.The sensitivity of FLI vs HRI was 56.3%,specificity 86.5%,PPV 57.0%,and NPV 86.1%.The diagnostic accuracy of FLI for steatosis > 5%,as predicted by SteatoTest,yielded an area under the receiver operating characteristic curve(AUROC) of 0.97(95% CI:0.95-0.98).The diagnostic accuracy of FLI for steatosis> 5%,as predicted by HRI,yielded an AUROC of 0.82(95% CI:0.77-0.87).The κ between diagnosis of fatty liver by AUS and by FLI(≥ 60) was 0.48 for the entire sample.However,after exclusion of all subjects with an intermediate FLI score of 30-60,the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65,representing good agreement.Excluding all the subjects with an intermediate FLI score,the sensitivity of FLI was 80.3% and the specificity 87.3%.Only 8.5% of those with FLI < 30 had fatty liver on AUS,but 27.8% of those with FLI ≥ 60 had normal liver on AUS.CONCLUSION:FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI.However,if intermediate values are excluded FLI has high diagnostic value vs AUS. | Shira Zelber-Sagi Muriel Webb Nimer Assy Laurie Blendis Hanny Yeshua Moshe Leshno Vlad Ratziu Zamir Halpern Ran Oren Erwin Santo | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 8 | Modulatory effect of International standard Scalp Acupuncture on brain activation in the elderly as revealed by resting-state fMRI显示文摘The specific mechanisms by which acupuncture affects the central nervous system are unclear. In the International Standard Scalp Acupuncture system, acupuncture needles are applied at the middle line of the vertex, anterior parietal-temporal oblique line, and the posterior parietal-temporal oblique line. We conducted a single-arm prospective clinical trial in which seven healthy elderly volunteers (three men and four women;50–70 years old) received International Standard Scalp Acupuncture at MS5 (the mid-sagittal line between Baihui (DU20) and Qianding (DU21)), the left MS6 (line joining Sishencong (EX-HN1) and Xuanli (GB6)), and the left MS7 (line joining DU20 and Qubin (GB7)). After acupuncture, resting-state functional magnetic resonance imaging demonstrated changes in the fractional amplitude of low frequency fluctuations and regional homogeneity in various areas, showing remarkable enhancement of regional homogeneity in the bilateral anterior cingulate, left medial frontal gyrus, supramarginal gyrus, right middle frontal gyrus, and inferior frontal gyrus. Functional connectivity based on a seed region at the right middle frontal gyrus (42, 51, 9) decreased at the bilateral medial superior frontal gyrus. Our data preliminarily indicates that the international standard scalp acupuncture in healthy elderly participants specifcally enhances the correlation between the brain regions involved in cognition and implementation of the brain network regulation system and the surrounding adjacent brain regions. The study was approved by the Ethics Committee of the China-Japan Union Hospital at Jilin University, China, on July 18, 2016 (approval No. 2016ks043). | Wai-Yeung Chung Song-Yan Liu Jing-Chun Gao Yi-Jing Jiang Jing Zhang Shan-Shan Qu Ji-Ping Zhang Xiao-Long Tan Jun-Qi Chen Sheng-Xu Wang | 2019 | Neural Regeneration Research2019，14，12： | 8 |
| 9 | Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma显示文摘AIM: To determine whether the serum level of matrix metalloproteinase-7 (MMP7) has the potential to diagnosis cholangiocarcinoma from benign biliary tract diseases. METHODS: This study was performed according to the PRoBE (a prospective-specimen-collection, retrospectiveblinded-evaluation) design. A total of 187 patients with obstructive jaundice were consecutively enrolled. After the diagnostic status of these patients was ascertained, their levels of serum MMP7 were assayed and compared with serum carbohydrate antigen 19-9 (CA19-9). This was conducted in a blinded case (cholangiocarcinoma)control (benign biliary tract disease) setup. RESULTS: MMP7 and CA19-9 serum levels were significantly elevated in cholangiocarcinoma patients (P < 0.001). The area under the curve (AUC) from a receiver operating characteristic (ROC) curve analysis for thediagnosis of cholangiocarcinoma, using MMP7 was more accurate than CA19-9 (AUC = 0.84, 95% CI: 0.778-0.903 for MMP7 and AUC = 0.79, 95% CI: 0.708-0.868 for CA19-9). The sensitivity and specificity of serum MMP7 (cut-off value of 5.5 ng/mL) was 75% and 78%, respectively, while the sensitivity and specificity of serum CA19-9 (cut-off value of 100 U/mL) was 68% and 87%, respectively. CONCLUSION: Serum values of MMP7 and CA19-9 appear to be useful biomarkers for differentiating cholangiocarcinoma from benign biliary tract obstructive diseases. | Kawin Leelawat Siriluck Narong Jerasak Wannaprasert Thawee Ratanashu-ek | 2010 | World Journal of Gastroenterology2010，16，37： | 7 |
| 10 | Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma显示文摘AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography(CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma.METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled.In the primary analysis, patients with successful EUSfine needle aspiration(FNA) were included. The lymph nodes were assessed by several standard EUS variables(short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel(CIV) presence] and CH-EUS variable(heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUSFNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection.RESULTS: One hundred and nine patients(143 lymph nodes) fulfilled the criteria. The short axis cutoff ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS.CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases. | Takeshi Miyata Masayuki Kitano Shunsuke Omoto Kumpei Kadosaka Ken Kamata Hajime Imai Hiroki Sakamoto Naoshi Nisida Yogesh Harwani Takamichi Murakami Yoshifumi Takeyama Yasutaka Chiba Masatoshi Kudo | 2016 | World Journal of Gastroenterology2016，22，12： | 7 |
| 11 | The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease显示文摘Alzheimer’s disease(AD)is a chronic neurodegenerative disease,which is associated with learning and memory impairment in the elderly.Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen.In a number of recent studies,inhibitors of histone deacetylase(HDACs)have been found to be a novel promising therapeutic agents for neurological disorders,particularly for AD and other neurodegenerative diseases.Although HDAC inhibitors have the ability to ameliorate cognitive impairment,successful treatments in the classic AD animal model are rarely translated into clinical trials.As for the reduction of unwanted side effects,the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be addressed.The review focused on literatures on epigenetic mechanisms in recent years,especially on histone acetylation in terms of the enhancement of specificity,efficacy and avoiding side effects for treating AD. | Shuang-shuang Yang Rui Zhang Gang Wang Yong-fang Zhang | 2017 | Translational Neurodegeneration2017，6，1： | 6 |
| 12 | Kudo's pit pattern classification for colorectal neoplasms:A meta-analysis显示文摘AIM:To analyze the current available evidence of Kudo's pit pattern classification for diagnosing colorectal neoplasms.METHODS:A search was performed on Pubmed/Embase to identify studies reporting the outcomes of the pit pattern classification in colorectal polyps.Retrieved records were evaluated and selected by two independent investigators.The number of patients,polyps and diagnostic performance of Kudo’s pit pattern classification were retrieved from suitable studies.Pooled sensitivities and specificities were calculated using fixed or random effect models according to their heterogeneity.Publication bias was evaluated using funnel plot,Egger’s test,and Begg’s test.Sensitivity analysis was performed by omitting one study at a time and selecting a subgroup consisting of 11 magnifying chromoendoscopy studies.RESULTS:20 eligible studies were included in which a total of 5111 colorectal lesions in 3418 patients were identified for the differentiation of neoplastic and nonneoplastic polyps.Pit pattern classification in all the studies of mucosal patterns with magnification resulted in a pooled sensitivity of 89.0%(95%CI:85.2-91.9)and pooled specificity of 85.7%(95%CI:81.3-89.2)and the area under the SROC curve was 0.9354.There was significant publication bias(P=0.038 and 0.006 for sensitivity and specificity using Egger’s test,P=0.035and 0.139 for sensitivity and specificity using Begg’s test,respectively).No single study significantly affected the pooled result,and the magnifying chromoendoscopy subgroup yielded a sensitivity of 92.7%(95%CI:89.2-95.2)and specificity of 87.3%(95%CI:81.6-91.4).CONCLUSION:Kudo’s pit pattern classification is an accurate diagnostic method for the differentiation of neoplastic colorectal lesions.Publication bias is significant in the current available literature. | Ming Li Syed Mohsin Ali Syeda Umm-a-OmarahGilani Jing Liu Yan-Qing Li Xiu-Li Zuo | 2014 | World Journal of Gastroenterology2014，20，35： | 5 |
| 13 | Assessment of tumor markers CA 19-9,CEA,CA 125,and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer显示文摘BACKGROUND Gallbladder cancer(GBC)is one of the leading and aggressive cancers in this region of India.It is very difficult to diagnose in the early stage,as it lacks typical early signs and symptoms;thus,the diagnosis is often in the advanced stage,which ultimately leads to a poor 5-year survival outcome.Tumor markers including carbohydrate antigen 19-9(CA 19-9),carcinoembryonic antigen(CEA),CA 125,CA 242,and alpha fetoprotein are used as indicators in the diagnosis and prognosis of GBC.AIM To compare tumor marker levels between GBC and benign GB diseases(GBDs)and to assess the combined use of tumor markers to increase the diagnostic accuracy for GBC.METHODS Patients of either sex aged≥18 years,with suspected GBC(GB polyp,irregular thick GB wall,GB mass,porcelain GB)on the basis of radiological imaging were included in this study.GB wall thickness using ultrasonography and tumor markers CEA,CA 125,CA 19-9,and CA 242 in all patients were recorded.All cases after surgical intervention were divided into two groups,GBC and benign GBD,according to histopathological examination findings.The cases were followed up and clinical findings,radiological findings,and levels of tumor markers were assessed.RESULTS A total of 200 patients were included in this study,of whom 80 patients had GBC and 120 patients had benign GBD.The median(interquartile range)age was 52.0(41.0-60.0)years and the majority of patients(132,66.0%)were women.Tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly elevated in patients with GBC(P<0.001).There was a significant reduction in tumor markers at 3 and 6 mo from baseline(P<0.001).The mean survival of patients with normal and elevated levels of tumor markers CA 125,CA 19-9,and CEA was comparable;however lymph node metastasis and CA 242 expression level were independent prognostic factors.CONCLUSION Serum levels of tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly associated with GBC.However,no significant association was observed between the presence of elevated levels of any tumor marker with respect to survival.Tumor marker assessment during follow-up may represent a treatment response. | Seema Rani Sinha Prem Prakash Rakesh Kumar Singh Dinesh Kumar Sinha | 2022 | World Journal of Gastrointestinal Surgery2022，14，11： | 5 |
| 14 | Targeting circular RNAs as a therapeutic approach: current strategies and challenges显示文摘Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in the pathogenesis of various diseases.CircRNAs are highly stable and usually expressed in a tissue-or cell type-specific manner.Therefore,they are currently being explored as potential therapeutic targets.Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies,respectively.These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems.Furthermore,recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner.While still in the early stages of development,the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency.In this review,we describe circRNA properties and functions and highlight their significance in disease.We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach.Lastly,we discuss major challenges and propose future directions for the development of circRNA-based therapeutics. | Alina T.He Jinglei Liu Feiya Li Burton B.Yang | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 5 |
| 15 | An Intramolecular Charge Transfer and Aggregation Induced Emission Enhancement Fluorescent Probe Based on 2-Phenyl-1,2,3-triazole for Highly Selective and Sensitive Detection of Homocysteine and Its Application in Living Cells显示文摘Summary of main observation and con elusion In this work,a new simple and readily synthesized turn-on probe 2-(4-anthracene-9-yl-phenyl)-2H-[l,2,3]triazole-4-carbaldehyde(APTC)was legitimately designed towards homocysteine(Hcy).Moreover,APTC has excellent optical properties such as intramolecular charge transfer(ICT)and aggregation induced emission enhancement(AIEE)characteristics,indicating its extensive application potentiality.What's more,APTC displayed rapid,high selectivity and specificity towards homocysteine over cysteine/glutathione.The detection limit of APTC for Hcy was as low as 2.198×10^-8 mol·L^-1,and the response time was only 5 min.APTC has been successfully applied to detect Hcy in silica gel plates and living cells,which indicates that APTC has good stability and biocompatibility as a selective probe for Hcy.Finally,the mechanism was studied using 1H NMR titration experiments and mass spectrometry. | Yicheng Chu Zhengfeng Xie Daijiao Zhuang Yongshuang Yue Yuhua Yue Wei Shi Shun Feng | 2019 | Chinese Journal of Chemistry2019，37，12： | 5 |
| 16 | THE EXTENSIVENESS AND SPECIFICITY OF EFFECT OF ELECTROACUPUNCTURE AT DIFFERENT ACUPOINTS ON NOCICEPTIVE RESPONSE OF CONVERGENT NEURONS IN TRIGEMINAL NUCLEUS CAUDALIS显示文摘Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral ' Xiaguan' (ST 7 on face ) or 'Zusanli' (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at 'Xiaguan' butnot 'Zusanlil', showing the specificity of acupoints. High intensity EA at either 'Xiaguan' or 'Zusan-li' also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that 'the gate of control' mechanism plays a main role in low intensity EA and 'diffuse noxiousinhibitory controls' (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints, | Xu Weidong, Liu Xiang. Zhu Bing. He Xiaoling. Zhang ShouxinInstitute of Acupuncture and Moxibustion, China Academy of TCM Beijing 100700, China | 1995 | World Journal of Acupuncture-Moxibustion1995，5，2： | 5 |
| 17 | Clinical,radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis显示文摘Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible. | Guadalupe Garcia-Elorriaga Olga Martinez-Elizondo Guillermo del Rey-Pineda Cesar Gonzalez-Bonilla | 2014 | Asian Pacific Journal of Tropical Biomedicine2014，4，7： | 5 |
| 18 | Primed macrophages directly and specifically reject allografts显示文摘Monocytes and macrophages have long been associated with acute and chronic allograft rejection;this is mediated by their abilities to promote inflammation,kill target cells via antibody-dependent cytotoxicity and modulate adaptive immunity.Our present study showed that allogeneic antigen-primed macrophages acutely rejected skin grafts with specificity after adoptive transfer into MHC-matched immunodeficient mice.The ability of primed macrophages to reject allografts essentially requires the help of CD4^(+) T cells and does not require the help of CD8^(+) T cells.Moreover,the primed,perforin-deficient macrophages rejected the skin grafts in a significantly delayed pattern compared with WT macrophages,indicating that the perforin pathway of the primed macrophages is likely involved in the rejection process.Thus,primed macrophages are endowed with adaptive immunitylike features,such as specificity,with the help of CD4^(+) T cells during the immune response to allografts.The present study challenges our traditional views of macrophage functions and highlights the biological functions of macrophages beyond innate immunity in mammals. | Zhulang Chu Chenming Sun Lina Sun Chang Feng Fan Yang Yanan Xu Yong Zhao | 2020 | Cellular & Molecular Immunology2020，17，3： | 4 |
| 19 | Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers显示文摘Cervical cancer is the leading cause of death among women with cancer worldwide.Here,we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation markers.We first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene expression.The DNA methylation profiles of 12 types of cancers,including cervical cancer,were used to generate a candidate set,and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate set.Then,we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal tissues.Promoter methylation was negatively correlated with the local regulation of gene expression.In the distant regulation of gene expression,the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression,while the methylation of hypomethylated genes was more likely to be positively correlated with gene expression.Moreover,we identified four cervical cancer-specific methylation markers,cg07211381(RAB3C),cg12205729(GABRA2),cg20708961(ZNF257),and cg26490054(SLC5A8),with 96.2%sensitivity and 95.2%specificity by using the tenfold cross-validation of TCGA data.The four markers could distinguish tumors from normal tissues with a 94.2,100,100,and 100%AUC in four independent validation sets from the GEO database.Overall,our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies. | Wanxue Xu Mengyao Xu Longlong Wang Wei Zhou Rong Xiang Yi Shi Yunshan Zhang Yongjun Piao | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 4 |
| 20 | A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor显示文摘Glucagon-like peptides(GLP-1 and GLP-2)are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors(GLP-1R and GLP-2R)which are important drug targets for metabolic disorders and Crohn's disease,respectively.Despite great progress in GLP-1 R structure determination,our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive.Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a Gs heterotrimer.To accommodate GLP-2 rather than GLP-1,GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices(TMs)1,5,7 and extracellular loop 1(ECL1).In contrast to GLP-1,the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation.The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2,and the GLP-2 C-terminus closely attaches to ECL1,which is the most protruded among 9 class B G protein-coupled receptors(GPCRs).Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation,especially the middle region.These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics. | Wen Sun Li-Nan Chen Qingtong Zhou Li-Hua Zhao Dehua Yang Huibing Zhang Zhaotong Cong Dan-Dan Shen Fenghui Zhao Fulai Zhou Xiaoqing Cai Yan Chen Yan Zhou Sarina Gadgaard Wijnand JCvan der Velden Suwen Zhao Yi Jiang Mette MRosenkilde HEric Xu Yan Zhang Ming-Wei Wang | 2020 | Cell Research2020，30，12： | 4 |
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