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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

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Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

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Neural Regeneration Research 2024年第9期19卷 2075-2080页

作者： Rui Zong Xuemei Li Chunyu Yin Jianfeng He Dekang Zhang Xiangbing Bian Lichao Huang Jiayou Zhou Zhipei Ling Lin Ma Xin Lou Longsheng Pan Xinguang Yu Seniro Department of Neurosurgery The First Medical Center of the PLA General HospitalBeijingChina Clinics of Cadre Department of OutpatientThe First Medical Center of the PLA General HospitalBeijingChina Department of Radiology The First Medical Center of the PLA General HospitalBeijingChina

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA general hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

关键词： efficacy essential tremor magnetic resonance-guided focused ultrasound(MRgFUS) movement disorder safety stereotactic therapy thalamotomy ventral intermediate nucleus

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Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1980-1989页

作者： Fang Li Bin Zhao Yong-Qiang Liu Guo-Qing Chen Rong-Feng Qu Chao Xu Zhui Long Jin-Song Wu Mao Xiong Wei-Hang Liu Li Zhu Xiao-Ling Feng Lei Zhang Department of general Surgery Chongqing General HospitalChongqing 401147China

BACKGROUND This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula,expanding the differential diagnosis for gastrointestinal bleeding.It emphasizes the importance of considering vascular origins in cases of atypical hematochezia,particularly in the absence of common gastrointestinal causes,and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations.CASE SUMMARY A 75-year-old man with a history of hypertension presented with 12 d of hematochezia,experiencing bloody stools 7-8 times per day.Initial computed tomography(CT)scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development.Hemoglobin levels progressively decreased to 7 g/dL.Emergency arterial angiography and iliac arterycovered stent placement were performed,followed by balloon angioplasty.Despite initial stabilization,minor rectal bleeding and abdominal pain persisted,leading to further diagnostic colonoscopy.This identified a neoplasm and potential perforation at the proximal rectum.An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall,necessitating partial rectal resection,intestinal anastomosis,and ileostomy.Postoperative recovery was successful,with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months.CONCLUSION In cases of unusual gastrointestinal bleeding,it is necessary to consider vascular causes for effective diagnosis and intervention.

关键词： Iliac artery aneurysm Hematoma Rectum Hematochezia Case report

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Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 514-526页

作者： Stylianos Fiflis Grigorios Christodoulidis Menelaos Papakonstantinou Alexandros Giakoustidis Stergos Koukias Paraskevi Roussos Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Dimitrios Giakoustidis First Department of Surgery General Hospital PapageorgiouThessaloniki 56429Greece Department of general Surgery University Hospital of LarissaLarissa 41110Greece

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed

关键词： Prognostic nutritional index Gastric adenocarcinoma Gastroesophageal junction cancer Prognosis Overall survival

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Advances in the molecular genetics of parathyroid tumors

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Chinese Medical Journal 2024年第3期137卷 376-378页

作者： Liwei Zhao Xianghui He Department of general Surgery Tianjin Medical University General HospitalTianjin 300052China

To the Editor:Parathyroid tumors are endocrine tumors that can lead to disorders of calcium and phosphorus metabolism and involve multiple organ systems.In the past,the genetics of parathyroid tumors have been well established,and the significant roles of genes such as MEN1,CDC73,and CCND1 in the process of parathyroid tumorigenesis have been identified and confirmed[Table 1].However,with further research and the widespread use of sequencing technology,“new”roles for“old”genes and new pathogenic mechanisms have been discovered.

关键词： metabolism tumors parathyroid

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Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

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Journal of Geriatric Cardiology 2024年第2期21卷 135-152页

作者： The Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon(2^(nd)Edition) Jun-Bo GE Yun-Dai CHEN 不详 Zhongshan hospital Fudan University Chinese PLA general hospital

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

关键词： balloon drugs dealing

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Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1869-1877页

作者： Bang Liu Zhao-Xiong Zhang Xin-Yang Nie Wei-Lin Sun Yong-Jia Yan Wei-Hua Fu Department of general Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University general hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.

关键词： T4N0M0 colon cancer Prognosis Multivariate analysis Nomogram Colon cancer

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Predictive factors for percutaneous nephrolithotomy bleeding risks

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Asian Journal of Urology 2024年第1期11卷 105-109页

作者： U Phun Loo Chun Hou Yong Guan Chou Teh Urology Department Sarawak General HospitalKuchingMalaysia

Objective:This study aimed to identify predictive factors for percutaneous nephrolithotomy(PCNL)bleeding risks.With better risk stratification,bleeding in high-risk patient can be anticipated and facilitates early identification.Methods:A prospective observational study of PCNL performed at our institution was done.All adults with radio-opaque renal stones planned for PCNL were included except those with coagulopathy,planned for additional procedures.Factors including gender,co-morbidities,body mass index,stone burden,puncture site,tract dilatation size,operative position,surgeon's seniority,and operative duration were studied using stepwise multivariate regression analysis to identify the predictive factors associated with higher estimated hemoglobin(Hb)deficiency.Results:Overall,4.86%patients(n=7)received packed cells transfusion.The mean estimated Hb deficiency was 1.3(range 0-6.5)g/dL and the median was 1.0 g/dL.Stepwise multivariate regression analysis revealed that absence of hypertension(p=0.024),puncture site(p=0.027),and operative duration(p=0.023)were significantly associated with higher estimated Hb deficiency.However,the effect sizes are rather small with partial eta-squared of 0.037,0.066,and 0.038,respectively.Observed power obtained was 0.621,0.722,and 0.625,respectively.Other factors studied did not correlate with Hb difference.Conclusion:Hypertension,puncture site,and operative duration have significant impact on estimated Hb deficiency during PCNL.However,the effect size is rather small despite adequate study power obtained.Nonetheless,operative position(supine or prone),puncture number,or tract dilatation size did not correlate with Hb difference.The mainstay of reducing bleeding in PCNL is still meticulous operative technique.Our study findings also suggest that PCNL can be safely done by urology trainees under supervision in suitably selected patient,without increasing risk of bleeding.

关键词： Percutaneous nephrolithotomy Predictive factor Risk factor Bleeding Blood loss

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Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases:Mechanisms and future perspectives

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World Journal of Gastroenterology 2024年第5期30卷 429-439页

作者： Ya-Wei Bi Long-Song Li Nan Ru Bo Zhang Xiao Lei Department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Radiation Oncology Chinese PLA General HospitalBeijing 100853China

Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.

关键词： Nicotinamide adenine dinucleotide phosphate hydrogen oxides Pancreatitis Pancreatic cancer Reactive oxygen species Mechanism

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Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

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World Journal of Stem Cells 2024年第5期16卷 525-537页

作者： Fang Li Bin Zhao Lei Zhang Guo-Qing Chen Li Zhu Xiao-Ling Feng Meng-Jia Gong Cheng-Chen Hu Yuan-Yuan Zhang Ming Li Yong-Qiang Liu Department of general Surgery Chongqing General HospitalChongqing 401147China Department of Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqing 401147China

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferatio

关键词： Urine-derived stem cells Regenerative medicine Acute kidney injury Renal function recovery Cell therapy

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