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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

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Neural Regeneration Research 2025年第7期20卷 2053-2067页

作者： Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic Laboratory for Neurobiology Department of General Physiology and BiophysicsFaculty of BiologyUniversity of BelgradeBelgradeSerbia Medical Faculty of Military Medical Academy University of DefenceBelgradeSerbia

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's *** therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in *** transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's ***,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain *** purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated *** with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod ***,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate *** intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate *** with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor *** treatment with prolonged intermittent theta burst stimulation,complete motor recovery was *** improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst *** results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)***

关键词： A_(1)R A_(2A)R adenosine receptors adenosine ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling

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Laparoscopic hepaticoplasty using gallbladder as a subcutaneous tunnel for hepatolithiasis

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World Journal of Gastroenterology 2014年第12期20卷 3350-3355页

作者： Long Cui Zhi Xu Xiao-Feng Ling Li-Xin Wang Chun-Sheng Hou Gang Wang Xiao-Si Zhou department of general surgery Peking University Third Hospital

AIM: To investigate the feasibility, efficacy and safety of laparoscopic hepaticoplasty using gallbladder as subcutaneous tunnel and sphincter-of-Oddi preservation for hepatolithiasis.

关键词： Hepatolithiasis Laparoscopy Hepaticoplasty Minimally invasive surgery Subcutaneous tunnel

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MiR-205 mediated APC regulation contributes to pancreatic cancer cell proliferation

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World Journal of Gastroenterology 2019年第28期25卷 3775-3786页

作者： Rui-Feng Qin Jia Zhang Hao-Ran Huo Zeng-Jiang Yuan Jia-Dong Xue third department of general surgery Handan Central Hospital

BACKGROUND Pancreatic cancer is a deadly malignancy with aggressive properties. MicroRNAs (miRNAs) participate in the pathogenesis of a variety of diseases and molecular processes by targeting functional mRNAs. Nevertheless, the regulatory role of miRNAs in signaling pathways involved in pancreatic cancer remains largely unknown. AIM To explore the molecular regulation involved in pancreatic cancer and potential mechanisms of miR-205. METHODS Microarray analysis was performed to investigate the expression profile of miRNAs in pancreatic cancer. Expression of miR-205 was validated by qRT-PCR. Target prediction and functional enrichment analysis were employed to seek potential target genes of miR-205 and potential functions of these genes. The target binding of miR-205 and adenomatous polyposis coli (APC) was validated by luciferase reporter assay. APC protein expression in pancreatic cancer was validated by qRT-PCR and Western blot. Proliferation was evaluated by MTT and colony formation assays. RESULTS A large number of miRNAs with altered expression were identified in pancreatic cancer. MiR-205 was significantly up-regulated. APC was found to be a validated target of miR-205 and down-regulated in pancreatic cancer. Proliferation experiments showed that miR-205 could promote cell proliferation in pancreatic cancer by targeting APC. CONCLUSION The above findings suggested that miR-205 mediated APC regulation contributes to pancreatic cancer development, which could be considered as a novel prognostic biomarker for clinical care.

关键词： Pancreatic cancer Microarray MiR-205 Adenomatous polyposis coli Proliferation

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Duodenum-preserving resection and Roux-en-Y pancreatic jejunostomy in benign pancreatic head tumors

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World Journal of Gastroenterology 2014年第44期20卷 16786-16792页

作者： Chun-Hui Yuan Ming Tao Yi-Mu Jia Jing-Wei Xiong Tong-Lin Zhang Dian-Rong Xiu department of general surgery Peking University Third Hospital

This study was conducted to explore the feasibility of partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of benign tumors of the pancreatic head(BTPH). From November 2006 to February 2009, four patients(three female and one male) with a mean age of 34.3 years(range: 21-48 years) underwent partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of BTPH(diameters of 3.2-4.5 cm) using small incisions(5.1-7.2 cm). Preoperative symptoms include one case of repeated upper abdominal pain, one case of drowsiness and two cases with no obvious preoperative symptoms. All four surgeries were successfully performed. The mean operative time was 196.8 min(range 165-226 min), and average blood loss was 138.0 m L(range: 82-210 m L). The mean postoperative hospital stay was 7.5 d(range: 7-8 d). In one case, the main pancreatic duct was injured. Pathological examination confirmed that one patient suffered from mucinous cystadenoma, one exhibited insulinoma, and two patients had solid-pseudopapillary neoplasms. There were no deaths or complications observed during the perioperative period. All patients had no signs of recurrence of the BTPH within a follow-up period of 48-76 mo and had good quality of life without diabetes. Partial pancreatic head resection with Roux-en-Y pancreatic jejunostomy is feasible in selected patients with BTPH.

关键词： Pancreatic benign tumor Pancreatic head Partial resection Roux-en-Y pancreatic jejunostomy Postoperative complications

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang department of Oncology The Fifth Medical Center of Chinese PLA General Hospital department of Thoracic surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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Oddi sphincter preserved cholangioplasty with hepaticosubcutaneous stoma for hepatolithiasis

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World Journal of Gastroenterology 2015年第45期21卷 12865-12872页

作者： Yu-Gui Lian Wei-Tao Zhang Zhi Xu Xiao-Feng Ling Li-Xin Wang Chun-Sheng Hou Gang Wang Long Cui Xiao-Si Zhou department of general surgery Peking University Third Hospital

AIM: To evaluate the long-term outcomes of Oddi sphincter preserved cholangioplasty with hepaticosubcutaneous stoma(OSPCHS) and risk factors for recurrence in ***: From March 1993 to December 2012, 202 consecutive patients with hepatolithiasis underwent OSPCHS at our department. The Oddi sphincter preserved procedure consisted of common hepatic duct exploration, stone extraction, hilar bile duct plasty, establishment of subcutaneous stoma to the bile duct. Patients with recurrent stones can undergo stone extraction and/or biliary drainage via the subcutaneous stoma which can be incised under local anesthesia. The long-term results were reviewed. Cox regression model was employed to analyze the risk factors for stone ***: Ninety-seven(48.0%) OSPCHS patients underwent hepatic resection concomitantly. The rate of surgical complications was 10.4%. There was no perioperative death. The immediate stone clearance rate was 72.8%. Postoperative cholangioscopic lithotomy raised the clearance rate to 97.0%. With a median follow-up period of 78.5 mo(range: 2-233 mo), 24.8% of patients had recurrent stones, 2.5% had late development of cholangiocarcinoma, and the mortality rate was 5.4%. Removal of recurrent stones and/or drainage of inflammatory bile via subcutaneous stoma were conducted in 44(21.8%) patients. The clearance rate of recurrent stones was 84.0% after subsequent choledochoscopic lithotripsy via subcutaneous *** regression analysis showed that residual stone was an independent prognostic factor for stone ***: In selected patients with hepatolithiasis, OSPCHS achieves excellent long-term outcomes, and residual stone is an independent prognostic factor for stone recurrence.

关键词： Hepatolithiasis Stone recurrence Sphincter of Oddi

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina department of general Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

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HBV recurrence lowered by lamivudine/HBIG combination therapy in liver transplant patients:ten-year experience

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 149-153页

作者： Chun-Hui Yuan Dian-Rong Xiu Bin Jiang Zhi-Fei Li Lei Li Shi-Bing Song Tong-Lin Zhang department of general surgery Peking University Third Hospital

BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group) The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared. RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P0.05). CONCLUSION: Compared with lamivudine monotherapy combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation.

关键词： hepatitis B virus recurrence lamivudine hepatitis B immunoglobulin liver transplantation

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Improvement of gastric emptying by enhanced recovery after pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2016年第2期15卷 198-208页

作者： Efstratios Zouros Theodoros Liakakos Anastasios Machairas Paulos Patapis Christos Agalianos Christos Dervenis department of surgery "Konstantopouleio" General Hospital First department of surgery Laiko University Hospital third department of surgery Attikon University Hospital

BACKGROUND： Enhanced recovery after surgery（ERAS） has improved postoperative outcomes particularly in colorectal surgery. This study aimed to assess compliance with an ERAS protocol and evaluate its effect on postoperative outcomes in patients undergoing pancreaticoduodenectomy. METHODS： Fifty patients who had received conventional peri operative management from 2005 to 2009（conventional group）were compared with 75 patients who had received perioperative care with an ERAS protocol（fast-track group） from 2010 to2014. Mortality, complications, readmissions and length of hospital stay were evaluated and compared in the ***： Compliance with each element of the ERAS pro tocol ranged from 74.7% to 100%. Uneventful patients had a significant higher adherence to the ERAS protocol（87.5% vs40.7%; P〈0.001）. There were no significant differences in de mographics and perioperative characteristics between the two groups. Patients in the fast-track group had a shorter time to remove the nasogastric tube, start liquid diet and solid food pass flatus and stools, and remove drains. No difference was found in mortality, relaparotomy, readmission rates and over all morbidity. However, delayed gastric emptying and length of hospital stay were significantly reduced in the fast-track group. The independent effect of the ERAS protocol in reduc ing delayed gastric emptying and length of hospital stay was confirmed by multivariate ***： ERAS pathway was feasible and safe in improving gastric emptying, yielding an earlier postoperative recovery, and reducing the length of hospital stay.

关键词： fast-track delayed gastric emptying compliance length of hospital stay morbidity

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An end-to-end anastomosis model of guinea pig bile duct:A 6-mo observation

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World Journal of Gastroenterology 2011年第6期17卷 789-795页

作者： Xiao-Qing Zhang Yuan-Hu Tian Zhi Xu Li-Xin Wang Chun-Sheng Hou Xiao-Feng Ling Xiao-Si Zhou department of general surgery Peking University Third Hospital Beijing 100191 China

AIM:To establish the end-to-end anastomosis (EEA) model of guinea pig bile duct and evaluate the healing process of bile ***:Thirty-two male guinea pigs were randomly divided into control group,2-,3-,and 6-mo groups after establishment of EEA ***,immunohistochemical and serologic tests as well as measurement of bile contents were *** bile duct diameter and the diameter ratio (DR) were measured to assess the formation of relative ***:Acute and chronic inflammatory reactions occurred throughout the healing process of bile *** test and bile content measurement showed no formation of persistent stricture in 6-mo *** DR revealed a transient formation of relative stricture in 2-mo group in comparation to control group (2.94 ± 0.17 vs 1.89 ± 0.27,P=0.004).However,this relative stricture was released in 6-mo group (2.14 ± 0.18,P=0.440).CONCLUSION:A simple and reliable EEA model of guinea pig bile duct can be established with a good reproducibility and a satisfactory survival rate.

关键词： Animal model Guinea pig Anastomosis Common bile duct Wound healing

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