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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of pathology Henry Ford HospitalDetroitMIUSA division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

Characteristic clinical features of Aspergillus appendicitis:Case report and literature review

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World Journal of Gastroenterology 2015年第44期21卷 12713-12721页

作者： Mihajlo Gjeorgjievski Mitual B Amin Mitchell S Cappell division of Gastroenterology and Hepatology William Beaumont Hospital anatomic pathology William Beaumont Hospital Oakland university William Beaumont School of Medicine

This work aims to facilitate diagnosing Aspergillus appendicitis, which can be missed clinically due to its rarity, by proposing a clinical pentad for Aspergillus appendicitis based on literature review and one new case. The currently reported case of pathologicallyproven Aspergillus appendicitis was identified by computerized search of pathology database at William Beaumont hospital, 1999-2014. Prior cases were identified by computerized literature search. Among 10980 pathology reports of pathologically-proven appendicitis, one case of Aspergillus appendicitis was identified(rate = 0.01%). A young boy with profound neutropenia, recent chemotherapy, and acute myelogenous leukemia presented with right lower quadrant pain, pyrexia, and generalized malaise. Abdominal computed tomography scan showed a thickened appendiceal wall and periappendiceal inflammation, suggesting appendicitis. Emergent laparotomy showed an inflamed, thickened appendix, which was resected. The patient did poorly postoperatively with low-grade-fevers while receiving antibacterial therapy, but rapidly improved after initiating amphotericin therapy. Microscopic examination of a silver stain of the appendectomy specimen revealed fungi with characteristic Aspergillus morphology, findings confirmed by immunohistochemistry. Primary Aspergillus appendicitis is exceptionally rare, with only 3 previously reported cases. All three cases presented with(1)-neutropenia,(2)-recent chemotherapy,(3)-acute leukemia, and(4)-suspected appendicitis;(5)-the two prior cases initially treated with antibacterial therapy, fared poorly before instituting antiAspergillus therapy. The current patient satisfied all these five criteria. Based on these four cases, a clinical pentad is proposed for Aspergillus appendicitis: clinically-suspected appendicitis, neutropenia, recent chemotherapy, acute leukemia, and poor clinical response if treated solely by antibacterial/anti-candidial therapy. Patients presenting with this propos

关键词： Aspergillosis Aspergillus appendicitis Fungal appe

Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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World Journal of Clinical Cases 2024年第1期12卷 176-179页

作者： Hsin-Chia Angela Lin Kam-Fai Lee Tzu Hao Huang division of General Surgery Department of SurgeryChang Gung Memorial HospitalChiayi 613Taiwan Department of anatomic pathology Chang Gung Memorial HospitalChiayi 613Taiwan

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric *** our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a *** describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based ***,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary *** SUMMARY The patient suffered from epigastric pain for several *** and computed tomography scan revealed a submucosal *** diagnoses included GIST,leiomyoma,teratoma,and mucinous ***,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach *** We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

关键词： IgG4-related disease Gastrointestinal stromal tumor Child Pediatric Case report

Ileo-ileal intussusception caused by lymphangioma of the small bowel treated by single-incision laparoscopic-assisted ileal resection

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World Journal of Gastroenterology 2017年第1期23卷 167-172页

作者： Atsushi Kohga Akihiro Kawabe Yuto Hasegawa Kiyoshige Yajima Takuya Okumura Kimihiro Yamashita Jun Isogaki Kenji Suzuki Akira Komiyama division of Surgery Fujinomiya City General Hospital division of pathology Fujinomiya City General Hospital

Intraabdominal lymphangiomas are uncommon;additionally,those affecting the gastrointestinal tract are rare and account for less than 1%of *** caused by a cystic lymphangioma of the small bowel is extremely *** patient was a20-year-old woman who visited our emergency room with a complaint of abdominal pain.A computed tomography image revealed ileo-ileal intussusception with a leading hypovascular mass measuring 1 cm in a ***-incision laparoscopic-assisted ileal resection was *** surgical specimen consisted of a soft polycystic ***,a pedunculated polyp with a convolutional pattern was ***,the inner surfaces of the cysts were covered with a single layer of endothelial *** immunohistochemical examination,the endothelial cells were partially positive for D2-40 and *** muscle cells were also found around the *** lesion was diagnosed as a cystic *** of cases of small bowel lymphangiomas have previously been *** these,cases with intussusception were very *** is the first case of small bowel intussusception due to lymphangioma treated by singleincision laparoscopic-assisted surgery.

关键词： Intussusception Single-incision laparoscopic-assisted surgery Lymphangioma

Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine

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World Journal of Gastroenterology 2015年第9期21卷 2700-2710页

作者： Reiko Kumagai Kenichi Kohashi Shunsuke Takahashi Hidetaka Yamamoto Minako Hirahashi Kenichi Taguchi Kenichi Nishiyama Yoshinao Oda Department of anatomic pathology Pathological SciencesGraduate School of Medical SciencesKyushu UniversityFukuoka 812-8582Japan Department of pathology National Hospital Organization Kyushu Cancer CenterFukuoka 811-1395Japan division of pathology Japanese Red Cross Fukuoka HospitalFukuoka 815-8555Japan

AIM:To clarify the correlation with phenotypic expression,clinicopathological features,genetic alteration and microsatellite-instability status in small intestinal adenocarcinoma(SIA).METHODS:The cases of 47 patients diagnosed with primary SIAs that were surgically resected at our institution in 1975-2005 were *** reviewed clinicopathological findings(age,gender,tumor size,gross appearance,histological morphologic type,invasion depth,lymphatic permeation,venous invasion,and lymph node metastasis),and the immunohistochemical expression of MUC5 AC,MUC6,MUC2,CD10,and mismatch-repair(MMR) proteins(MLH1 and MSH2).We analyzed KRAS and BRAF gene mutations,and the microsatellite instability(MSI) *** immunohistochemical staining of CD10,MUC2,MUC5 AC and MUC6 was considered positive when distinct staining in > 5% of the adenocarcinoma cells was *** evaluate of MMR protein expression,we used adjacent normal tissue including lymphoid follicles,inflammatory cells,and stromal cells as an internal positive *** without nuclear staining in the tumor cells were considered to have lost the expression of the respective MMR ***:There were 29 males and 18 females patients(mean age 59.9 years,range:23-87 years).Tumors were located in the duodenum in 14 cases(30%),the jejunum in 21 cases(45%),and the ileumin 12 cases(25%).A phenotypic expression analysis revealed 20 MUC2-positive tumors(42.6%),11 MUC5AC-positive(23.4%),4 MUC6-positive(8.5%),and 7 CD10-positive(14.9%).The tumor sizes of the MUC2(+) tumors were significantly larger than those of the MUC2(-) tumors(mean,5.7 ± 1.4 cm vs 4.7 ± 2.1 cm,P < 0.05).All three tumors with adenomatous component were positive for MUC2(P < 0.05).Polypoid appearance was seen significantly more frequently in the CD10(+) group than in the CD10(-) group(P < 0.05).The tumor size was significantly larger in the CD10(+) group than in the CD10(-) group(mean,5.9 ± 1.4 cm vs 5.0 ± 2.1 cm,P < 0.05).Of 34 SIAs with succ

关键词： Small intestine Adenocarcinoma Mucin CD10 Microsat

Single-center Experience in the Diagnosis and Treatment of Hepatic Perivascular Epithelioid Cell Neoplasm

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 72-79页

作者： Junjun Jia Jia Luo Cheng-Gen Pan Guomei Ge Meibao Feng Bei Zou Li Liu Shusen Zheng Jun Yu division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangChina Department of pathology The First Affiliated Hospi-talCollege of MedicineHangzhouZhejiangChina Department of Library The First Affiliated HospitalZhejiang Univer-sity School of MedicineHangzhouZhejiangChina

Background and Aims:Perivascular epithelioid cell neo-plasms(PEComas)are a rare type of mesenchymal neo-plasm and their preoperative diagnosis is *** this study,we summarized the experience from a single medical center to study the examinations,clinical presen-tations,and pathological and histological characteristics of PEComas in the liver in order to optimize overall un-derstanding of the diagnosis and treatment of these ***:We conducted a retrospective analysis to investigate the clinical and pathological characteristics as well as imaging presentations of 75 patients diagnosed with hepatic PEComa in The First Affiliated hospital of Zhe-jiang university between April 2010 and April ***-sults:Among the 75 patients,52 were women,and the median age was 48 *** patients had no specific symptoms,and two were admitted to the hospital for a second time owing to *** patients underwent surgi-cal ***,38 patients had classical angio-myolipoma(AML)and 37 had epithelioid *** PECo-mas were accompanied by positive immunohistochemical expression of HMB45,Melan-A,and smooth muscle ***-up data were obtained from 47 of the total 75 pa-tients,through October *** patients had metastasis after ***:AML is the most common type of hepatic *** are no specific symptoms of he-patic PEComa,and serological examinations and imaging modalities for accurate preoperative diagnosis are *** AML should be considered a tumor of uncertain malignant potential;however,the prognosis of PEComa af-ter resection is promising.

关键词： Liver Perivascular epithelioid cell neoplasms Diagnosis Treatment

Colorectal cancers in ulcerative colitis from a low-prevalence area for colon cancer

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World Journal of Gastroenterology 2015年第12期21卷 3644-3649页

作者： Devendra Desai Sudeep Shah Abhijit Deshmukh Philip Abraham Anand Joshi Tarun Gupta Ramesh Deshpande Varun Khandagale Siji George division of Gastroenterology P.D Hinduja Hospital division of Gastrointestinal surgery Department of Surgery P.D Hinduja Hospital division of pathology Department of Pathology P.D Hinduja Hospital

AIM: To determine the incidence and risk factors for colorectal cancer(CRC) in patients with ulcerative colitis from a low prevalence region for ***: Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men(57.7%)] with ulcerative colitis(median disease duration 6, range: 1-39 years) for analysis. Of these, 131(30.5%) had left-sided colitis and 159(37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of ***: Twelve patients(2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease- 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained ***: CRC occurred in 2.8% of patients with ulcerative colitis in our population- an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our *** risk increased with extent and duration of disease.

关键词： Colon cancer Dysplasia Epidemiology Inflammatory b

Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

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World Journal of Gastroenterology 2015年第14期21卷 4385-4390页

作者： Akinori Shirahige Haruhisa Suzuki Ichiro Oda Masau Sekiguchi Genki Mori Seiichiro Abe Satoru Nonaka Shigetaka Yoshinaga Shigeki Sekine Ryoji Kushima Yutaka Saito Takeo Fukagawa Hitoshi Katai Endoscopy division National Cancer Center Hospital pathology division National Cancer Center Hospital Department of Clinical Laboratory Medicine and Diagnostic pathology Shiga University of Medical Science Gastric Surgery division National Cancer Center Hospital

An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection(ESD) for early gastric cancer(EGC).Two years after the initial ESD, a 0-Ⅱc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric *** estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated *** was performed for this lesion and en bloc resection with negative margins was *** examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer(1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative *** gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical *** chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second *** gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well *** present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.

关键词： Early gastric cancer Endoscopic submucosal dissect