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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency medicine FuzhouFujian ProvinceChina The Second department of intensive care unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Proton pump inhibitors and all-cause mortality risk among cancer patients

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World Journal of Clinical Oncology 2025年第1期16卷 34-42页

作者： Arunkumar Krishnan Carolin Victoria Schneider Declan Walsh department of Supportive Oncology Atrium Health Levine CancerCharlotteNC 28204United States department of medicine Section of Hematology and OncologyWake Forest University School of MedicineWinston-SalemNC 27101United States department of medicine Ⅲ GastroenterologyMetabolic Diseasesand Intensive CareUniversity Hospital RWTH AachenAachen 52074Germany

BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related *** evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater *** To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize *** This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare *** study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer *** prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)*** primary outcome was all-cause *** patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding *** Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these *** a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individual

关键词： All-cause mortality Cancer Histamine-2 receptor antagonists Mortality Malignancy Proton pump inhibitors Carcinoma Outcome

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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Effects of Electro-Acupuncture at Zusanli,Guanyuan for Sepsis Patients and Its Mechanism through Immune Regulation

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Chinese Journal of Integrative medicine 2016年第3期22卷 219-224页

作者：杨广胡瑞英邓霭静黄羽李健 intensive care unit Guangdong Provincal Hospital of Traditional Chinese Medicine intensive care unit Wuhan Hospital of Traditional Chinese Medicine

Objective： TO evaluate the effect of electro-acupuncture on Zusanli （ST 36）, Guanyuan （RN 4） in patients with sepsis, and explore its mechanism in term of immune regulation. Methods： In this prospective randomized controlled trial, 60 patients with sepsis were randomly assigned to the control group and the intervention group equally by block randomization. Patients in the control group received routine treatment and those in the intervention group received electro-acupuncture at bilateral Zusanli and Guanyuan in addition to routine treatment, respectively. The mortality at 28 days, Acute Physiology and Chronic Health Evaluation （APACHE）- II score were compared to evaluate the effect, and the levels of T cell subsets （CD3＋, CD4＋, CD8＋, CD4＋/CD8＋） and monocytes of human leukocyte antigen （HLA）-DR using flow cytometry were compared to explore the mechanism of this combined treatment. ]Results： Fifty-eight patients completed the trial with 29 in each group. There was no significant difference of mortality in the 28th day between the two groups, with 5 death of 29 patients in the intervention group （17.2%） and 9 of 29 in the control group （31.0%）. After treatment, APACHE-11 score of both groups was significantly decreased, however, score of the intervention group was lower than the control group （13.28＋7.07 vs. 17.10＋5.83; P〈0.01）. The levels of CD3＋, CD4＋, CD8＋ and CD4＋/CD8＋ ratio of the intervention group improved after treatment and were higher than the control group （59.71% ± 11.94% vs. 52.54% ±11.86%; 36.46% ± 7.60% vs. 31.58%± 10.23%; 18.40%±8.82% vs. 23.07% ± 7.30%; 2.38± 1.14 vs. 1.54±0.80, respectively; all P〈0.05）. The expression of HLA-DR significantly increased after treatment in the intervention group than that in the control group （7.28% ± 9.26% vs. 1.27% ± 7.00%; P〈0.01）. Conclusion： Electro-acupuncture at Zusanli and Guanyuan could improve clinical curative effect in patients with sepsis, which might be achieved by regulation of the immune system.

关键词： sepsis electro-acupuncture ST36 RN4 immunohematology clinical trial

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Real-world evidence on the efficacy and safety of vonoprazanamoxicillin dual therapy for Helicobacter pylori treatment in elderly patients

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World Journal of Gastroenterology 2025年第1期31卷 68-78页

作者： Wen Gao Jing-Wen Li Hui Ye Xue-Zhi Zhang Jian-Xiang Liu Hong Cheng department of Gastroenterology Peking University First HospitalBeijing 100034China School of medicine Tsinghua MedicineTsinghua UniversityBeijing 100034China department of Traditional Chinese medicine and Integrative medicine Peking University First HospitalBeijing 100034China

BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(***).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly *** To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for *** in elderly *** As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for *** eradication in the department of Gastroenterology at Peking University First Hospital between June 2020 and January *** status was evaluated by^(13)C-urease breath test 6 weeks after *** adverse events(AEs)during treatment were *** In total,401 cases were ***-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take *** total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue *** was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment *** overall incidence of AEs was 9.5%for both ***,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment *** patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE *** The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.

关键词： Helicobacter pylori Vonoprazan Amoxicillin Dual therapy Elderly

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of Pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Changes in intestinal microflora in rats with acute respiratory distress syndrome

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World Journal of Gastroenterology 2014年第19期20卷 5849-5858页

作者： Yan Li Xiang-Yong Liu Ming-Ming Ma Zhi-Jiang Qi Xiao-Qiang Zhang Zhi Li Guo-Hong Cao Jun Li Wei-Wei Zhu Xiao-Zhi Wang department of Respiratory medicine and intensive care unit Affiliated Hospital of Binzhou Medical University department of intensive care unit Zhangqiu People’s Hospital department of Cell Biology Binzhou Medical University department of intensive care unit Dezhou People’s Hospital

AIM: To implement high-throughput 16S rDNA sequencing to study microbial diversity in the fecal matter of rats with acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

关键词： Lipopolysaccharide Acute lung injury Acute respiratory distress syndrome Intestinal microflora High-throughput sequencing

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Heat shock protein 70 protects PC12 cells against ischemia-hypoxia/reoxygenation by maintaining intracellular Ca^(2+) homeostasis

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Neural Regeneration Research 2016年第7期11卷 1134-1140页

作者： Yuan Liu Xue-chun Wang Dan Hu Shu-ran Huang Qing-shu Li Zhi Li Yan Qu department of intensive care unit Affiliated Qingdao Municipal Hospital of Qingdao University department of intensive care unit Affiliated Hospital of Jining Medical University

Heat shock protein 70（HSP70） maintains Ca^2＋ homeostasis in PC12 cells,which may protect against apoptosis;however,the mechanisms of neuroprotection are ***,in this study,we examined Ca^2＋ levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct,and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation ***70 overexpression increased neuronal viability and ATPase activity,and it decreased cellular reactive oxygen species levels and intracellular Ca^2＋ concentration after hypoxia/***70 overexpression enhanced the protein and m RNA expression levels of sarcoplasmic/endoplasmic reticulum Ca^2＋-ATPase（SERCA）,but it decreased the protein and m RNA levels of inositol 1,4,5-trisphosphate receptor（IP3R）,thereby leading to decreased intracellular Ca^2＋concentration after ischemia-hypoxia/*** results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury,at least in part,by maintaining cellular Ca^2＋ homeostasis,by upregulating SERCA expression and by downregulating IP_3 R expression.

关键词： homeostasis intracellular reticulum neuronal endoplasmic maintaining ATPase unclear minutes exogenous

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Fanlian Huazhuo formula:A promising therapeutic approach for metabolic associated steatotic liver disease

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World Journal of Gastroenterology 2025年第1期31卷 167-171页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of *** study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and *** editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.

关键词： Fanlian Huazhuo formula Metabolic associated steatotic liver disease Autophagy Lipid metabolism Oxidative stress

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Extracorporeal membrane oxygenation as a bridging therapy for patients with thiamine deficiency-induced pulmonary arterial hypertension

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World Journal of Emergency medicine 2024年第2期15卷 147-149页

作者： Fangfang Qiu Weixing Dai Tengyue Huang Min Li department of intensive care unit the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China department of intensive care unit the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009China

Thiamine deficiency is characterized by a deficiency of thiamine(vitamin B1),lactic acidosis,pulmonary arterial hypertension(PAH),right-sided heart failure,and peripheral nerve *** deficiency is easily misdiagnosed and missed during clinical practice and is associated with death in severe cases.[1,2]Here we reported a patient who was admitted to the hospital with severe metabolic acidosis and pulmonary hypertension and finally diagnosed with thiamine deficiency by detecting plasma vitamin B1 *** clinically obvious thiamine deficiency is rare,and cases of thiamine deficiency requiring extracorporeal membrane oxygenation(ECMO)treatment are rarer,we believe that our case will be helpful for emergency clinicians.

关键词： vitamin hypertension arterial

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