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| 1 | 抗糖尿病药物有助于治疗阿尔茨海默病和帕金森病(英文)显示文摘2型糖尿病已被证实是阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)的一个危险因素。已有报道表明,AD和PD患者脑内的胰岛素信号转导受到损害。这一发现使抗糖尿病药物的应用有了新的研究,并显示出良好效应。临床前期试验表明,胰岛素或长效肠促胰岛素肽(incretin peptide)类似物具有良好的神经保护作用。在AD和PD转基因模型动物中,胰高血糖素样肽1(GLP-1,一种肠促胰岛素的类似物)阻止了神经退行性变进程,改善了神经元和突触的功能,并减轻了疾病的症状。在AD转基因小鼠模型中,GLP-1类似物阻止了淀粉样斑块的沉积、突触的丧失以及认知功能的损害;在PD动物模型中,GLP-1类似物改善了多巴胺能神经传递和运动功能。在此基础上,临床试验也在进行之中,并显示出令人鼓舞的结果。在AD患者中的初步研究表明,鼻腔给予胰岛素可改善患者的认知功能并减少脑内的AD标志物。对PD患者的初步研究也表明,目前已经上市用于治疗2型糖尿病的一种GLP-1受体激动剂(exendin-4,Byetta)对PD病人具有良好的疗效。另一种上市用于治疗糖尿病的GLP-1类似物(liraglutide,Victoza)也正在AD患者中进行临床测试。最近,第三种GLP-1受体激动剂(Lixisenatide,Lyxumia)已经在欧洲被批准上市,该药物也显示了良好的神经保护作用。本文将就以上抗糖尿病药物的神经保护作用进行归纳。可见,GLP-1类似物所显示的神经保护乃至神经再生作用为AD和PD提供了一种新的治疗手段,这些作用是当前其它药物所不具备的。 | Christian Hlscher | 2014 | 生理学报2014，66，5： | 17 |
| 2 | Co-expression of CDX2 and MUC2 in gastric carcinomas: Correlations with clinico-pathological parameters and prognosis显示文摘AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia.METHODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including χ2 tests, uni- and multi-variate survival analyses were performed.RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern, whereas MUC2 showed an almost exclusive supranuclear reactivity. Both antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the carcinomas. The presence of both molecules did not correlate with WHO,significantly stronger vlUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity. A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype. | Kristina Roessler Stefan P.M(o|¨)nig Paul M.Schneider Franz-Georg Hanisch Stephanie Landsberg Juergen Thiele Arnulf H.H(o|¨)lscher Hans P.Dienes Stephan E.Baldus | 2005 | World Journal of Gastroenterology2005，11，21： | 15 |
| 3 | Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual receptor agonist DA-CH5 is superior to exendin-4 in protecting neurons in the 6-hydroxydopamine rat Parkinson model显示文摘Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular coagonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine(6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1(IRS-1)/alpha serine/threonine-protein kinase(Akt)/c AMP response element-binding protein(CREB) pathway. We also found that DA-CH5(10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines(tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was upregulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDAunilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China. | Ling-Yu Zhang Qian-Qian Jin Christian Hölscher Lin Li | 2021 | Neural Regeneration Research2021，16，8： | 10 |
| 4 | Treatment of early gastric cancer in the Western World显示文摘The incidence rate of gastric cancer is much higher in Asia than in the Western industrial nations.According to the different screening programs in Japan and Korea about fifty percent of treated patients had an early tumor stage.In contrast,European and American patients with gastric cancer had an advanced tumor stage.Therefore,the experience for the various therapeutic options for gastric cancer may be different between these regions.In this review we tried to point out the treatment modalities in Western industrial countries for early gastric cancer. | Elfriede Bollschweiler Felix Berlth Christoph Baltin Stefan Mnig Arnulf H Hlscher | 2014 | World Journal of Gastroenterology2014，20，19： | 8 |
| 5 | Regional lymphadenectomy strongly recommended in T1b gallbladder cancer显示文摘This article discusses the adequate treatment of early gallbladder cancer(T1a,T1b) and is based on published studies extending over nearly 3 decades.Randomized studies and meta analyses comparing different surgical treatments do not exist.The literature shows that in up to 20% of patients lymph node metastasis are found in T1b gallbladder cancer.Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand,and the relative low operative risk of extended cholecystectomy(cholecystectomy and regional lymphadenectomy) on the other hand,we believe that this procedure is mandatory in early gallbladder cancer. | Ulrich Klaus Fetzner Arnulf H Hlscher Dirk L Stippel | 2011 | World Journal of Gastroenterology2011，17，38： | 8 |
| 6 | Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma显示文摘AIM: To investigate the role of cytochrome P450 (CYP) in the carcinogenesis of squamous-cell carcinoma (SCC) in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS: mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC (n = 21) and in controls (n = 10). Protein levels of CYP2E1, CYP2C8, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS: Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue (-39% and -74%, respectively, P < 0.05) than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients (4.8-, 2.9-, and 1.9-fold elevation, P < 0.05) than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients (+46%, P < 0.05). CONCLUSION: Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue (e.g. CYP2C8, CYP3A4, CYP3A5, and CYP2E1) between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus. | I Bergheim E Wolfgarten E Bollschweiler AH Hlscher C Bode A Parlesak | 2007 | World Journal of Gastroenterology2007，13，7： | 6 |
| 7 | Scalable and controlled self-assembly of aluminum-based random plasmonic metasurfaces显示文摘Subwavelength metal-dielectric plasmonic metasurfaces enable light management beyond the diffraction limit.However,a costeffective and reliable fabrication method for such structures remains a major challenge hindering their full exploitation.Here,we propose a simple yet powerful manufacturing route for plasmonic metasurfaces based on a bottom-up approach.The fabricated metasurfaces consist of a dense distribution of randomly oriented nanoscale scatterers composed of aluminum(Al)nanohole-disk pairs,which exhibit angle-independent scattering that is tunable across the entire visible spectrum.The macroscopic response of the metasurfaces is controlled via the properties of an isolated Al nanohole-disk pair at the nanoscale.In addition,the optical field confinement at the scatterers and their random distribution of sizes result in a strongly enhanced Raman signal that enables broadly tunable excitation using a single substrate.This unique combination of a reliable and lithography-free methodology with the use of aluminum permits the exploitation of the full potential of random plasmonic metasurfaces for diagnostics and coloration. | Radwanul Hasan Siddique Jan Mertens Hendrik Hölscher Silvia Vignolini | 2017 | Light(Science & Applications)2017，6，1： | 5 |
| 8 | Nighttime sap flow of Acacia mangium and its implications for nighttime transpiration and stem water storage显示文摘Aims Nighttime sap flow of trees may indicate transpiration and/or recharge of stem water storage at night.This paper deals with the water use of Acacia mangium at night in the hilly lands of subtropical South China.Our primary goal was to reveal and understand the nature of nighttime sap flow and its functional significance.Methods Granier’s thermal dissipation method was used to determine the nighttime sap flux of A.mangium.Gas exchange system was used to estimate nighttime leaf transpiration and stomatal conductance of studied trees.Important Findings Nighttimesap flowwas substantial and showed seasonal variation similar to the patterns of daytime sap flowin A.mangium.Mean nighttime sap flow was higher in the less precipitation year of 2004(1122.4 mm)than in the more precipitation year of 2005(1342.5 mm)since more daytime transpiration and low soil water availability in the relatively dry 2004 can be the cause of more nighttime sap flow.Although vapor pressure deficit and air temperature were significantly correlated with nighttime sap flow,they could only explain a small fraction of the variance in nighttime sap flow.The total accumulated water loss(E_(L))by transpiration of canopy leaves was only;2.6–8.5%of the total nighttime sap flow(E_(t))during the nights of July 17–18 and 18–19,2006.Therefore,it is likely that the nighttime sap flow was mainly used for refillingwater in the trunk.The stem diameter at breast height,basal area and sapwood area explained much more variance of nighttime water recharge than environmental factors and other tree form features,such as tree height,stem length below the branch,and canopy size.The contribution of nighttime water recharge to the total transpiration ranged from 14.7 to 30.3%depending on different DBH class and was considerably higher in the dry season compared to the wet season. | Hua Wang Ping Zhao Dirk Hölscher Quan Wang Ping Lu Xi A.Cai Xiao P.Zeng | 2012 | Journal of Plant Ecology2012，5，3： | 5 |
| 9 | Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment显示文摘Patients with advanced esophageal cancer(T3-4, N) have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response(regression to less than 10% of the primary tumor) after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [18F]-fluorodeoxyglucose-positron emission tomography(FDGPET) has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response. | Elfriede Bollschweiler Arnulf H.Hlscher Matthias Schmidt Ute Warnecke-Eberz | 2015 | Chinese Journal of Cancer Research2015，27，3： | 3 |
| 10 | New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases显示文摘Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable. | Christian H?lscher | 2014 | Neural Regeneration Research2014，9，21： | 3 |
| 11 | Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer显示文摘AIM:To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer.METHODS:Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals.Allelic discrimination was performed by quantitative real-time polymerase chain reaction.Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression.RESULTS:Thirty-nine(32%) patients displayed a CC genotype,57(46.7%) a CT genotype and 26(21.3%) a TT genotype.The frequency of the C allele(fC) in the patient group was 0.55,which was not signif icantly different from that of healthy blood donors.The distribution was compatible with the Hardy-Weinberg equilibrium.Analysis of clinicopathological parameters did not show any signif icant correlation of the T393C genotype with gender(P=0.50),differentiation(P=0.29),pT-category(P=0.19),pN-category(P=0.30),pM-category(P=0.25),R-category(P=0.95),the classifications according to WHO(P=0.34),Laurén(P=0.16),Goseki(P=1.00) and Ming(P=0.74).Dichotomization between C+(CC+CT) and C-genotypes(TT),however,revealed signif icantly more advanced tumor stages(P=0.023) and lower survival rates(P=0.043) for C allele carriers.CONCLUSION:The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers. | Hakan Alakus Stefan P Mnig Ute Warnecke-Eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler Arnulf H Hlscher Ralf Metzger | 2009 | World Journal of Gastroenterology2009，15，48： | 3 |
| 12 | Introduction显示文摘 | A. H. Hlscher | 2004 | The Chinese-German Journal of Clinical Oncology2004，3，4： | 2 |
| 13 | Transthoracic En-bloc Esophagectomy显示文摘In patients with esophageal carcinoma surgical resection remains the standard of curative treatment. For locally advanced tumors (pT1sm–pT3) transthoracic esophagectomy with extended lym- phadenectomy is the standard surgical procedure since it o?ers a complete removal of the primary tumor and possible lymph node metastases. This surgical resection is appropriate for squamous cell but also adenocarcinoma of the esophagus because both histological entities demonstrate a lymphatic spread to the abdominal compartment and the upper mediastinum. In-hospital mortality rates are between 6% and 9%; anastomotic leakage and pulmonary complications mainly contribute to postoperative morbidity. In terms of 5-year survival the transthoracic procedure o?ers a better prognosis compared to the transhiatal resection. | W. Schrder P. M. Schneider A. H. Hlscher | 2004 | The Chinese-German Journal of Clinical Oncology2004，3，4： | 2 |
| 14 | 新型GLP-1/GIP双受体激动剂DA3-CH对大鼠癫痫持续状态后海马神经元凋亡的影响显示文摘目的探索新型胰高血糖素样肽-1/葡萄糖依赖性促胰岛素样肽(GLP-1/GIP)双受体激动剂DA3-CH对匹罗卡品诱导的大鼠癫痫持续状态(SE)后海马神经元凋亡的影响,进而探讨其神经保护作用.方法将108只体质量为250~300g的健康成年雄性SD大鼠随机分为正常对照组(NS组,n=12)、癫痫持续状态模型组(SE组,n=48)、DA3-CH干预组(SE+DA3组,n=48),SE组和SE+DA3组分别据造模成功后观察指标的不同时间点(SE后12h、1d、3d、7d)分为4个亚组(每个亚组n=12).腹腔注射匹罗卡品(30mg·kg^-1诱导SE模型,造模成功后,SE+DA3组大鼠每日进食前给予腹腔注射DA3-CH(101nmoL·kg^-1,NS组及SE组大鼠给予等体积生理盐水.各亚组分别于SE后12h、1d、3d、7d检测空腹尾静脉血糖水平后处死取脑,采用免疫组化和Western blot方法检测海马中凋亡相关蛋白Bax、Bcl-2及神经元核抗原NeuN的表达水平.结果①NS组、SE组、SE+DA3组各亚组大鼠之间的空腹尾静脉血糖水平差异无统计学意义(P>0.05);②免疫组化与Western blot结果显示,NS组、SE组、SE+DA3组各亚组大鼠之间海马Bax、Bcl-2、NeuN表达水平差异均有统计学意义(P<0.001);与NS组相比,SE组大鼠海马Bax、Bcl-2表达水平升高,NeuN表达水平降低;与SE组相比,SE+DA3组大鼠海马Bax表达水平降低,Bcl-2、NeuN表达水平升高.结论新型GLP-1/GIP双受体激动剂DA3-CH可抑制大鼠癫痫持续状态导致的海马神经元凋亡,减少神经元丢失,具有神经保护作用. | 田森晶 薛国芳 Christian H?lscher 张晓敏 孟鹏飞 袁振宇 | 2019 | 脑与神经疾病杂志2019，27，7： | 2 |
| 15 | Altered levels of the onco-microRNA 21 and the tumor-supressor microRNAs143 and 145 in advanced rectal cancer indicate successful neoadjuvant chemoradiotherapy显示文摘 | Uta Drebber Max Lay Inga Wedemeyer Daniel Vallb?hmer Elfriede Bollschweiler Jan Brabender Stefan M?nig Arnulf H?lscher Hans Dienes Margarete Odenthal | 2011 | International Journal of Oncology2011，，： | 2 |
| 16 | 食管黏膜下鳞状细胞癌及腺癌的高淋巴结转移率显示文摘Background and study aims: The application of endoscopic mucosectomy in early esophageal cancer is limited by the presence of lymph-node metastasis. The aim of this prospective study was to analyze the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor penetration, comparing squamous-cell carcinomas and adenocarcinomas. Patients and methods: A total of 60 patients with pT1 esophageal cancer- 24 with squamous-cell carcinomas (SCCs) and 36 with adenocarcinomas- were treated with transthoracic enbloc esophagectomy with two-field lymphadenectomy (n = 50) or transhiatal esophageal resection (n = 10). An average of 30 lymph nodes were examined, and the following characteristics were evaluated: histology, mucosal infiltration, depth of submucosal wall infiltration in three thirds (sm1, sm2, sm3), grading, resection category, ratio of metastatic to resected lymph nodes, and locations of metastatic nodes. Results: The rates of lymph-node metastasis were 0% for the 16 mucosal carcinomas and 45% for the 44 submucosal carcinomas (P< 0.01). There were no significant differences in the extent of lymph-node involvement between submucosal adenocarcinomas (41% ) and submucosal SCCs (50% ). Sm1 carcinomas were associated with a lower rate of lymph-node metastasis (SCCs 33% , adenocarcinomas 22% ) than sm3 carcinomas (SCCs 69% , adenocarcinomas 78% ). Two patients (9% ) with submucosal SCCs and five patients (23% ) with submucosal adenocarcinomas were classified as having stage pM1 lymph. The average lymph-node ratio in patients with pN1 was 0.13 for adenocarcinomas and 0.1 for SCCs (difference not significant). In the multivariate analysis, the parameters mucosal vs. submucosal (P < 0.01) and G1/G2 vs. G3 (P < 0.05) showed a significant impact in relation to metastatic lymph nodes. Conclusions: The most important factor for predicting lymph-node metastasis in early esophageal cancer is the presence of submucosal infiltration. Early adenocarcinomas and SCCs do not differ with regard to their rate of lymphatic involvement. The rate of lymph-node metastasis increases with the depth of submucosal infiltration, but metastases can already occur in sm1 lesions. Submucosal infiltration is a contraindication for endoscopic mucosectomy. Limited surgical procedures without adequate lymphadenectomy do not appear to be appropriate in the treatment of patients with submucosal esophageal carcinomas. | Bollschweiler E. Baldus S.E. Schrder W. A.H. Hlscher 张红凯 | 2006 | 世界核心医学期刊文摘(胃肠病学分册)2006，2，8： | 2 |
| 17 | Diagnostic und Therapies Magenkarzinoms-Workflow显示文摘 | Grundmann RT Hlscher AH Bembenek A | 2009 | Zentralbl Chir2009，134，： | 1 |
| 18 | Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography显示文摘 | Schlachetzki F H(o)lscher T Koch HJ | 2002 | J Ultrasound Med2002，21，4： | 1 |
| 19 | Maligne Tumoren der Hepaticusgabel – Ergebnisse der chirurgischen Therapie und Prognosefaktoren显示文摘 | K. T. E. Beckurts A. H. H?lscher T. H. Bauer J. R. Siewert | 1997 | Der Chirurg1997，，4： | 1 |
| 20 | The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis显示文摘 | Hlscher C Hlscher A Rückerl D | | 0，，06： | 1 |
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