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Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

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Type 2 diabetes is associated with a worse functional outcome of ischemic stroke

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World Journal of Diabetes 2014年第6期5卷 939-944页

作者： Konstantinos Tziomalos Marianna Spanou Stella D Bouziana Maria Papadopoulou Vasilios Giampatzis Stavroula Kostaki Vasiliki Dourliou Maria Tsopozidi Christos Savopoulos Apostolos I Hatzitolios First Propedeutic Department of Internal Medicine Medical SchoolAristotle University of ThessalonikiAHEPA Hospital

AIM: To assess whether ischemic stroke severity and outcome is more adverse in patients with type 2 diabetes mellitus(T2DM). METHODS: Consecutive patients hospitalized for acute ischemic stroke between September 2010 and June 2013 were studied prospectively(n = 482; 40.2% males, age 78.8 ± 6.7 years). T2 DM was defined as self-reported T2 DM or antidiabetic treatment. Stroke severity was evaluated with the National Institutes of Health Stroke Scale(NIHSS) score at admission. The outcome was assessed with the modified Rankin scale(m RS) score at discharge and with in-hospital mortality. Adverse outcome was defined as m RS score at discharge ≥ 2 or in-hospital death. The length of hospitalization was also ***: T2 DM was present in 32.2% of the study population. Patients with T2 DM had a larger waist circumference, higher serum triglyceride and glucose levels and lower serum high-density lipoprotein cholesterol levels as well as higher prevalence of hypertension, coronary heart disease and congestive heart failure than patients without T2 DM. On the other hand, diabetic patients had lower low-density lipoprotein cholesterol levels and reported smaller consumption of alcohol than non-diabetic patients. At admission, the NIHSS score did not differ between patients with and without T2DM(8.7 ± 8.8 and 8.6 ± 9.2, respectively; P = NS). At discharge, the m RS score also did not differ between the two groups(2.7 ± 2.1 and 2.7 ± 2.2 in patients with and without T2 DM, respectively; P = NS). Rates of adverse outcome were also similar in patients with and without T2DM(62.3% and 58.5%, respectively; P = NS). However, when we adjusted for the differences between patients with T2 DM and those without T2 DM in cardiovascular risk factors, T2 DM was independently associated with adverse outcome [relative risk(RR) = 2.39; 95%CI: 1.21-4.72, P = 0.012]. Inhospital mortality rates did not differ between patients with T2 DM and those without T2DM(9.0% and 9.8%, respectively;

关键词： Ischemic stroke functional outcome Severity Mortality Type 2 diabetes mellitus Cardiovascular disease Hyperglycemia Cardiovascular risk Dyslipidemia Hypertension

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Achilles tendon thickening does not affect elasticity and functional outcome after surgical repair of Achilles rupture:A retrospective study

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Chinese Journal of Traumatology 2023年第6期26卷 323-328页

作者： Chen-Xi Wu Chang-Yue Xiong Lu Bai Su-Meng Chen Yu-Xin Yan Lu Wang Xin-Tao Zhang Department of Sports Medicine Peking University Shenzhen Hospital Shenzhen518036Guangdong provinceChina Department of Statistics and Mathematical Sciences Southern University of Science and TechnologyShenzhen518055Guangdong provinceChina

Purpose:Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the *** this mechanism has been elucidated in the laboratory,there are few reports on its impact on clinical *** designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative ***:In this retrospective analysis,patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were *** the patients were regularly followed up at 3 months,1 year,and 2 years after *** Orthopaedic Foot Ankle Surgeon(AOFAS)scale and Leppilahti score were used to evaluate functional *** elasticity was measured by ultrasound shear wave of *** thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance *** t-tests was used for different follow-up *** between Achilles thickening and other factors were analyzed using Pearson's method.pfunctional scales were also improved at 2-year follow-up significantly(both p<0.001).The dorsiflexion difference showed gradually recovery in each follow-up period(t=-17.907,p<0.001).The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets(p<0.001).In thickening evaluation,the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively(310.5±25.2)mm^(2)than that at 3 months postoperatively((278.0±26.2)mm^(2),t=-8.219,p<0.001)and became thinner in 2-year magnetic resonance scan((256.1±15.1)mm^(2),t=16.769,p<0.001).The correlations between Achilles

关键词： Achilles tendon rupture Thickening Elasticity functional outcome

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Serum Gamma-glutamyl Transferase Levels Predict functional outcomes after Aneurysmal Subarachnoid Hemorrhage

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Biomedical and Environmental Sciences 2017年第3期30卷 170-176页

作者： XU Tian WANG Wei ZHAI Lin ZHANG Yun Feng ZHOU Hong Zhi WU Xin Min LI Ai Hong XIE Li Li NING Xiao Jin JI Yu Teng WANG Hong Mei KE Kai Fu Department of Neurology Affiliated Hospital of Nantong UniversityNantong 226001JiangsuChina Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjing 210006JiangsuChina Medical record center Affiliated Hospital of Nantong UniversityNantong 226001JiangsuChina Neurology research institute of Nantong University Nantong 226001JiangsuChina

Objective We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population. Methods A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ≥ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage. Results The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of 〈 30 U/L, 30-50 U/L and ≥ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively （P 〈 0.01）. The age-sex and multivariable adjusted odds ratios （95% confidence intervals） of poor prognosis comparing the top group （≥ 50 U/L） with the lowest group （〈 30 U/L） were 5.76 （2.74-12.13）, 6.64 （2.05-21.52）, and 6.36 （1.92-21.02）. A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers. Conclusion Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.

关键词： Aneurysmal subarachnoid hemorrhage Gamma-glutamyl transferase functional outcome Predictor

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Robot-assisted radical cystectomy with neobladder diversion in females:Safety profile and functional outcomes

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Asian Journal of Urology 2024年第4期11卷 618-624页

作者： Andrea Pacchetti Alberto Caviglia Vito Lorusso Nicolas Branger Thomas Maubon Stanislas Rybikowski Davide Perri Giorgio Bozzini Geraldine Pignot Jochen Walz Division of Urology Sant'Anna HospitalSan Fermo della BattagliaComoItaly Department of Urology ASST Grande Ospedale Metropolitano NiguardaMilanItaly Division of Urology ASST Fatebenefratelli SaccoMilanItaly Department of Urology Institut Paoli-Calmettes Cancer CentreMarseilleFrance

Objective Radical cystectomy(RC)is a standard treatment for localized muscle invasive bladder cancer and high-risk or very high-risk non-muscle invasive bladder cancer not responding to adequate endovesical *** women,traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall,often resulting in sexual ***-sparing techniques have been developed to improve functional *** present study explores the safety and the functional outcome of vaginal-sparing *** We retrospectively analyzed all consecutive female patients undergoing robot-assisted RC(RARC)with neobladder diversion between October 2017 and February *** indications for vaginal-sparing RC were absence of tumor on bladder neck or urethra and no sign of infiltration of posterior bladder wall at the preoperative *** results were evaluated with the aid of five questions out of the Bladder Cancer Index *** were reported according to the Clavien–Dindo classification and cancer control was evaluated by recurrence-free and cancer-specific *** A total of 22 female patients underwent RARC with neobladder *** chemotherapy was given in 17(77%)***–Dindo grades III–IV complications occurred in four(18%)*** a mean follow-up of 29(interquartile range 16–44)months,six(27.3%)patients developed distant metastases,and one(4.5%)woman loco-regional ***-sparing surgery was performed in 19(86%)patients,and in the others the anterior vaginal wall was resected,but neobladder was still *** daytime,no patients reported total incontinence and 73%(11/15)reported total continence or only occasional *** results showed that seven of 15(47%)women regained sexual activity after surgery,with a quality reported as“good”or“very good”in 40%of all 19 *** RARC in female with anterior vaginal wall preservation is *** approach showed

关键词： Sexual-sparing Robot-assisted radical cystectomy Female functional outcome Continence Sexual function

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functional outcomes of Adult Tibia Shaft Fractures Treated with Solid Intramedullary Nails versus Hollow Nails: A Systematic Review

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Open Journal of Orthopedics 2024年第3期14卷 149-172页

作者： Kwadwo Aning Abu Bernard Hammond Mohammed Issah Suglo Bukari Kizito Kakra Vormawor Ronald Awoonor-Williams David Anyitey-Kokor Paa Kwesi Baidoo Dominic Konadu-Yeboah Department of Orthopaedics St. John of God Hospital Duayaw Nkwanta Ghana Directorate of Trauma and Orthopaedics Komfo Anokye Teaching Hospital Kumasi Ghana Department of Surgery Tamale Teaching Hospital Tamale Ghana Department of Orthopadics and Trauma Seventh Day Adventist Hospital Asamang Ghana

Introduction: The management of fractures of the tibia shaft is an important aspect of orthopaedic care, and the selection of the surgical method for fixation can substantially impact patient outcomes. The current review aims to compare the outcomes of adult tibia fractures treated with solid nails to those treated with hollow nails. Methods: A search on Scopus, PubMed, and Cochrane Library, using three keywords (outcome, Tibia shaft fractures, Nail) was conducted in April 2023. Results were compiled and two independent reviewers screened and selected eligible articles After removing duplicates, titles and abstracts were read to exclude ineligible studies. Full-text articles of the remaining papers were read to select eligible studies which were further critically appraised to ascertain their methodological quality. The data extracted from the selected papers were synthesized using a combination of pooling of results, tests of statistical difference (t-test and chi-square) and narrative synthesis methods. Results: A total of 2295 articles were obtained from the databases and citation searching. A total of 9 papers were identified as eligible and included in the review. Findings revealed that there is no statistical difference in the outcomes of tibia fractures treated with either solid or hollow nail groups such as duration of surgery (p = 0.541), rate of delayed and non-union (p = 0.342), and rate of surgical site infections (p = 0.395). Conclusion: Intramedullary nailing of tibia shaft fractures with either solid or hollow nails have similar functional outcomes.

关键词： Tibia Shaft Fractures functional outcome SIGN Nail Hollow Nail

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functional outcomes of Decompressive Hemicraniectomy for Treatment of Malignant Infarctions of the Middle Cerebral Artery

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Open Journal of Modern Neurosurgery 2020年第3期10卷 307-317页

作者： Amr Mohsen Waleed Abbass Faculty of Medicine Cairo University Cairo Egypt

Introduction: Malignant middle cerebral artery (MCA) infarction is a devastating entity that is associated with up to 80% mortality. Decompressive Hemicraniectomy has been utilized to treat brain swelling and mass effect secondary to these infarctions in an attempt to improve functional outcome. Aim: To evaluate the functional outcome of decompressive hemicraniectomy in management of malignant MCA infarctions. Methods: The study included 30 patients with malignant MCA infarctions operated upon by decompressive hemicraniectomy and duroplasty with pericranium or fascia lata graft in the period from June 2016 to January 2019. Pre-operative neurological condition, associated morbidity, location and extent of the infarction were assessed. Surgery was performed within 48 hours of the onset of stroke or 12 hours within deterioration of conscious level. Pre-operative CT scan as well as sequential post-operative CT was done. functional outcome was assessed by the modified Rankin Scale (mRS) at the time of discharge and 3 months following surgery. Results: The study included 18 males and 12 females with a mean age of 54.7 years. The pre-operative GCS was functional outcome (mRS 0 - 3) was achieved in 13 (43.3%) cases while poor outcome (mRS 4 - 5) occurred in 8 (26.7%) cases and mortality (mRS 6) occurred in 9 (30%) cases. Conclusion: Decompressive hemicraniectomy improves functional outcome in cases of malignant MCA infarction. Pre-operative GCS, age, volume of infarction, degree of midline shift, timing of surgery and associated morbidity are the most important factors affecting the outcome.

关键词： Decompressive Hemicraniectomy Malignant MCA Infarction functional outcome Modified Rankin Scale

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Risk factors of mortality and severe disability in the patients with cerebrovascular diseases treated with perioperative mechanical ventilation

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World Journal of Clinical Cases 2022年第16期10卷 5230-5240页

作者： Jin-Zhu Zhang Hao Chen Xin Wang Kan Xu Department of Neurosurgery The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND The prognosis of cerebrovascular diseases treated with mechanical ventilation during perioperative has not been clearly *** To analyze mortality and functional disability and to determine predictors of unfavorable outcome in the patients with cerebrovascular diseases treated with mechanical *** A retrospective follow-up study of 111 cerebrovascular disease patients who underwent mechanical ventilation during the perioperative period in the First Hospital of Jilin University from June 2016 to June 2019 was *** measurements were mortality and functional outcome in-hospital and after 3-month *** to the modified rankin scale(mRS),the functional outcome was divided into three groups:Good recovery(mRS≤3),severe disability(mRS=4 or 5)and death(mRS=6).Univariate analysis was used to compare the differences between three functional *** logistic regression analysis was used to for risk factors of mortality and severe *** The average age of 111 patients was 56.46±12.53 years,59(53.15%)were *** mortality of in-hospital and 3-month follow-up were 36.9% and 45.0%,*** 71 discharged patients,46.47% were seriously disabled and 12.67% died after three months *** analysis showed that preoperative glasgow coma scale,operation start time and ventilation reasons had statistically significant differences in different functional *** logistic regression analysis showed that the cause of ventilation was related to the death and poor prognosis of patients with cerebrovascular *** with brainstem compression,the risk of death or severe disability of pulmonary disease,status epilepticus,impaired respiratory center function,and shock were 0.096(95%CI:0.028-0.328),0.026(95%CI:0.004-0.163),0.095(95%CI:0.013-0.709),0.095(95%CI:0.020-0.444),*** The survival rate and prognostic outcomes of patients with cerebrovascular diseas

关键词： Cerebrovascular diseases Mechanical ventilation Perioperative Mortality functional outcome

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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration

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Neural Regeneration Research 2024年第1期19卷 49-54页

作者： Ye Xiong Asim Mahmood Michael Chopp Department of Neurosurgery Henry Ford HospitalDetroitMIUSA Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Traumatic brain injury is a serious and complex neurological condition that affects millions of people *** significant advancements in the field of medicine,effective treatments for traumatic brain injury remain ***,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain *** vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and *** administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional *** preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor *** further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain *** this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

关键词： biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells neuroinflammation neuroplasticity neuroprotection traumatic brain injury

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Role of stem cells-based in facial nerve reanimation:A meta-analysis of histological and neurophysiological outcomes

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World Journal of Stem Cells 2022年第6期14卷 420-428页

作者： Luca Ricciardi Resi Pucci Amedeo Piazza Giorgio Lofrese Alba Scerrati Nicola Montemurro Antonino Raco Massimo Miscusi Tamara Ius Marco Zeppieri Division of Neurosurgery AOU Sant’AndreaDepartment of NESMOSSapienza UniversityRome 00189Italy Department of Oral and Maxillofacial Sciences Sapienza UniversityRome 00161Italy Division of Neurosurgery Ospedale BufaliniCesena 47521Italy Department of Neurosurgery Sant'Anna University HospitalS.Anna University HospitalFerrara 44121Italy Department of Morphology Surgery and Experimental MedicineUniversity of FerraraFerrara 44121Italy Department of Neurosurgery Azienda Ospedaliera Universitaria PisanaPisa 56126Italy Neurosurgery Unit Department of NeurosciencesSanta Maria della Misericordia University HospitalUdine 33100Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy

BACKGROUND Treatments involving stem cell(SC)usage represent novel and potentially interesting alternatives in facial nerve *** literature includes the use of SC in animal model studies to promote graft survival by enhancing nerve fiber growth,spreading,myelinization,in addition to limiting fibrotic degeneration after ***,the effectiveness of the clinical use of SC in facial nerve reanimation has not been clarified *** To investigate the histological,neurophysiological,and functional outcomes in facial reanimation using SC,compared to *** Our study is a systematic review of the literature,consistently conducted according to the preferred reporting items for systematic reviews and meta-analyses statement *** review question was:In facial nerve reanimation on rats,has the use of stem cells revealed as effective when compared to autograft,in terms of histological,neurophysiological,and functional outcomes?Random-effect meta-analysis was conducted on histological and neurophysiological data from the included comparative *** After screening 148 manuscript,five papers were included in our study.43 subjects were included in the SC group,while 40 in the autograft *** meta-analysis showed no significative differences between the two groups in terms of myelin thickness[CI:-0.10(-0.20,0.00);I^(2)=29%;P=0.06],nerve fibers diameter[CI:0.72(-0.93,3.36);I^(2)=72%;P=0.6],compound muscle action potential amplitude[CI:1.59(0.59,3.77);I^(2)=89%;P=0.15]and latency[CI:0.66(-1.01,2.32);I^(2)=67%;P=0.44].The mean axonal diameter was higher in the autograft group[CI:0.94(0.60,1.27);I^(2)=0%;P≤0.001].CONCLUSION The role of stem cells in facial reanimation is still relatively poorly studied,in animal models,and available results should not discourage their use in future studies on human subjects.

关键词： Facial nerve Palsy Reanimation Coaptation Stem cells Nerve fibers functional outcome

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