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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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clinical and Microbiological Characteristics of Patients with Complicated Intra-abdominal Infections in intensive care unit

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Current Medical Science 2020年第1期40卷 104-109页

作者： Yang-mei XIONG Xin RAO Department of intensive care unit Zhongnan Hospital of Wuhan UniversityWuhan 430071China

In order to investigate the clinical and microbiological characteristics of patients with complicated intra-abdominal infections(cIAIs)in intensive care unit(ICU),the clinical data of 612 cIAIs patients from January 2016 to December 2018 were retrospectively *** characteristics,distribution of pathogens and drug resistance were statistically *** was found that patients with community-acquired intra-abdominal infections(CA-IAIs)made up a majority of cIAIs *** positive rate of abdominal drainage fluid culture was 55.56%.Gramnegative bacteria accounted for the majority,the most commonly isolated bacteria of which were Escherichia coli(20.96%),Klebsiella pneumoniae(10.20%)and Pseudomonas aeruginosa(5.57%).The most commonly isolated gram-positive bacteria were Enterococcus(16.88%)and Methicillinresistant staphylococcus aureus(MRSA,3.90%).Enterobacter isolates showed high resistance rate to most cephalosporins and low resistance rate to piperacillin/tazobactam and *** spectrum beta-lactamase(ESBL)screen positive isolates from CA-IAIs patients showed an increasing trend in past three *** and MRSA showed high resistance rate to clindamycin,quinolone,erythromycin and tetracycline,while they showed high sensitivity rate to linezolid,tegacycline,teicoplanin and *** results indicate that isolated bacteria from abdominal drainage fluid show high resistance rates to commonly used antibiotics in ICU patients with *** curative effects on diseases should be monitored continuously when antibiotics are ***,we should always keep eyes on drug-resistant bacteria,especially when the treatment efficacy is not good.

关键词： complicated intra-abdominal infection pathogens extended spectrum beta-lactamase screen positive isolates resistance rate

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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma

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World Journal of Gastroenterology 2018年第37期24卷 4230-4242页

作者： Leonardo Lorente intensive care unit Hospital Universitario de Canarias

The outcome prediction of hepatocellular carcinoma(HCC) patients undergoing liver transplantation(LT) was classically established using various macromorphological factors and serum alpha-fetoprotein levels prior to LT. However, other biomarkers have recently been reported to be associated with the prognosis of HCC patients undergoing to LT. This review summarizes clinical data on these new biomarkers. High blood levels of malondialdehyde, total antioxidant capacity, caspasecleaved cytokeratin-18, soluble CD40 ligand, substance P, C-reactive protein, and vascular endothelial growth factor, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood, high peripheral blood expression of human telomerase reverse transcriptase messenger ribonucleic acid, and high HCC expression of dickkopf-1 have recently been associated with decreased survival rates. In addition, high blood levels of des-gamma-carboxy prothrombin, and high HCC expression of glypican-3, E-cadherin and betacatenin have been associated with increased HCC recurrence. Additional research is necessary to establish the prognostic role of these biomarkers in HCC prior to LT. Furthermore, some of these biomarkers are also interesting because their potential modulation could help to create new research lines for improving the outcomes of those patients.

关键词： Liver transplantation Hepatocellular carcinoma Biomarkers Outcome Survival Recurrence Genomic

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clinical features and outcomes of patients with severe acute pancreatitis complicated with gangrenous cholecystitis

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 317-323页

作者： Er-Zhen Chen Jie Huang Zhi-Wei Xu Jian Fei En-Qiang Mao Sheng-Dao Zhang Emergency intensive care unit Ruijin Hospital School of Medicine Shanghai Jiaotong University Surgical intensive care unit Ruijin Hospital School of Medicine Shanghai Jiaotong University

BACKGROUND: The effects of gangrenous cholecystitis (GC) and consequent surgical interventions on the clinical outcomes and prognosis of patients with severe acute pancreatitis are not clear. The present study was to characterize the clinical outcomes of patients with severe acute pancreatitis complicated with GC. METHODS: We retrospectively analyzed 253 consecutive patients hospitalized for acute pancreatitis in intensive care unit. Among them, 68 were diagnosed as having severe acute pancreatitis; 10 out of the 68 patients had GC. We compared these 10 patients with GC and 58 patients without GC. The indices analyzed included sepsis/septic shock, pancreatic encephalopathy, acute respiratory distress syndrome, acute renal failure, multiple organ dysfunction syndrome, and death. RESULTS: Specific CT images of GC in patients with severe acute pancreatitis included enlarged and high-tensioned gallbladder, wall thickening, lumenal emphysema, discontinuous and/or irregular enhancement of mucosa, and pericholecystic effusion. The rates of severe sepsis/septic shock (70.0% vs 24.1%, P<0.01), pancreatic encephalopathy (50.0% vs 17.2%, P<0.05), acute respiratory distress syndrome (90.0% vs 41.4%, P<0.01), multiple organ dysfunction syndrome (70.0% vs 24.1%, P<0.01), acute renal failure (40.0% vs 27.6%, P<0.05), and death (40.0% vs 13.8%, P<0.05) were significantly higher in patients with GC than in those without ***: CT scans can help to identify early GC in patients with severe acute pancreatitis; early diagnosis and intervention for patients with GC can reduce morbidity and mortality.

关键词： severe acute pancreatitis gangrenous cholecystitis surgical intervention

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Changes in thyroid function in patients with liver failure and their clinical significance:A clinical study of non-thyroidal illness syndrome in patients with liver failure

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 561-566页

作者： Hong-Ling Feng Qian Li Wu-Kui Cao Ji-Ming Yang intensive care unit Tianjin Second People’s HospitalTianjin 300192China

Background:Non-thyroidal illness syndrome(NTIS)develops in a large proportion of critically ill patients and is associated with high risk for *** aimed to investigate the correlation between NTIS and liver failure,and the short-term mortality of patients with these ***:The clinical data of 87 patients with liver failure were collected retrospectively,73 of them were randomly selected for an observational study and to establish prognostic models,and 14 for model *** 73 sex-and age-matched patients with mild chronic hepatitis were randomly selected as a control *** free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)were *** clinical characteristics of patients with liver failure and NTIS were *** follow-up of patients lasted for 3 ***,the values for predicting short-term mortality of model for end-stage liver disease(MELD),Child-Turcotte-Pugh(CTP),chronic liver failure-sequential organ failure assessment(CLIF-SOFA)scores,FT3-MELD model,and FT3 were ***:The observation group had significantly lower FT3(2.79±0.71 vs.4.43±0.75 pmol/L,P<0.001)and TSH[0.618(0.186-1.185)vs.1.800(1.570-2.590)mIU/L,P<0.001],and higher FT4(19.51±6.26 vs.14.47±2.19 pmol/L,P<0.001)than the control *** was diagnosed in 49 of the patients with liver failure(67.12%).In the observation group,patients with NTIS had a higher mortality rate than those without(63.27%vs.25.00%,P=0.002).Across the whole cohort,the 3-month mortality was 50.68%.The international normalized ratios(INR)were 2.40±1.41 in survivors and 3.53±1.81 in deaths(P=0.004),the creatinine(Cr)concentrations were 73.27±36.94μmol/L and 117.08±87.98μmol/L(P=0.008),the FT3 concentrations were 3.13±0.59 pmol/L and 2.47±0.68 pmol/L(P<0.001),the MELD scores were 22.19±6.64 and 29.57±7.99(P<0.001),the CTP scores were 10.67±1.53 and 11.78±1.25(P=0.001),and the CLIF-SOFA scores were 8.42±1.68 and 10.16±2.03(P<0.001),resp

关键词： Liver failure Non-thyroidal illness syndrome Free triiodothyronine Prognosis

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Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 271-275页

作者： Hong-Ling Feng Qian Li Lin Wang Gui-Yu Yuan Wu-Kui Cao intensive care unit Tianjin Second People's Hospital

BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is *** indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH ***: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of *** addition, the MELD scores and KCH criteria were ***: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-

关键词： acute liver failure indocyanine green clearance test model for end-stage liver disease prognosis

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Successful management of seven cases of critical COVID-19 with early noninvasive-invasive sequential ventilation algorithm and bundle pharmacotherapy

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Frontiers of Medicine 2020年第5期14卷 674-680页

作者： Mian Peng Xueyan Liu Jinxiu Li Di Ren Yongfeng Liu Xi Meng Yansi Lyu Ronglin Chen Baojun Yu Weixiong Zhong Department of intensive care unit The Third Affiliated Hospital of Shenzhen UniversityShenzhen 518001China Department of intensive care unit Shenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologyThe Second Affiliated Hospital of Jinan UniversityShenzhen 518020China Department of intensive care unit The Third People’s Hospital of ShenzhenShenzhen 518112China Department of intensive care unit The Second People's Hospital of ShenzhenShenzhen 518035China Department of intensive care unit Shenzhen Longgang Central HospitalShenzhen 518116China Department of Dermatology Shenzhen University General HospitalShenzhen 518055China Department of intensive care unit Shenzhen Baoan District People's HospitalShenzhen 518101China

We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019(COVID-19)requiring mechanical ventilation(MV).The patients were diagnosed based on epidemiological history,clinical manifestations,and nucleic acid *** diagnosis with COVID-19 of critical severity,the patients were admitted to the intensive care unit,where they received early noninvasive-invasive sequential ventilation,early prone positioning,and bundle pharmacotherapy regimen,which consists of antiviral,anti-inflammation,immune-enhancing,and complication-prophylaxis *** patients presented fever(n=7,100%),dry cough(n=3,42.9%),weakness(n=2,28.6%),chest tightness(n=1,14.3%),and/or muscle pain(n=1,14.3%).All patients had normal or lower than normal white blood cell count/lymphocyte count,and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the *** acid testing confirmed COVID-19 in all seven *** median MV duration and intensive care unit stay were 9.9 days(interquartile range,6.5-14.6 days;range,5-17 days)and 12.9 days(interquartile range,9.7-17.6 days;range,7-19 days),*** seven patients were extubated,weaned off MV,transferred to the common ward,and discharged as of the writing of this ***,we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive-invasive sequential ventilation and bundle pharmacotherapy.

关键词： COVID-19 noninvasive-invasive sequential ventilation bundle pharmacotherapy

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nutritional management of severe acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 603-604页

作者： Li-Peng Huang Shui-Fang Jin Rong-Lin Jiang intensive care unit Taizhou Cancer HospitalWenling 317502China intensive care unit First Affiliated HospitalZhejiang Chinese Medical UniversityHangzhou 310006China

Severe acute pancreatitis(SAP)is a common clinical emergency and critical *** increases of hyperlipidemic pancreatitis and alcoholic pancreatitis result in the increase of *** SAP mortality is as high as 30%[1].During the resuscitation and treat-ment of SAP,the metabolism changes require nutritional *** individual metabolic status need personalized nutrition ap-proach.

关键词： pancreatitis metabolism acute

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Effects of early enteral nutrition on Th17/Treg cells and IL-23/IL-17 in septic patients

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World Journal of Gastroenterology 2019年第22期25卷 2799-2808页

作者： Jia-Kui Sun Wen-Hao Zhang Wen-Xiu Chen Xiang Wang Xin-Wei Mu Department of intensive care unit Nanjing First Hospital Nanjing Medical University

BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P intensive care unit stay of the EEN group were shorter than those of the DEN group (P clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.

关键词： Early enteral nutrition Enteral nutrition T helper lymphocytes Th17/Treg cells IL-23/IL-17 axis Sepsis

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