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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

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Can we predict the incidence of high-grade Clavien-Dindo complications in patients with forgotten encrusted stents undergoing endourologic management?

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Asian Journal of Urology 2024年第1期11卷 99-104页

作者： Praanjal Gupta Ramanitharan Manikandan Lalgudi Narayanan Dorairajan Kodakattil Sreenivasan Sreerag Sidhartha Kalra Swapnil Singh Kushwaha Department of Urology Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherryIndia

Objective:Ureteral stents are customarily inserted to facilitate urinary drainage,but they come with their own glitches of being forgotten and/or encrusted leading to serious *** present study aimed to report the complications in patients with forgotten and encrusted stents according to the Clavien-Dindo system specific to urological procedures and identify the factors leading to high-grade(Clavien-Dindo Grade 4A or above)***:The hospital records of patients with forgotten encrusted double-J stents over a period of 8 years were *** parameters recorded included patient demographics,indwelling time,need for percutaneous nephrostomy,hemodialysis,urine culture,blood culture,total blood counts,serum creatinine,radiologic findings,management techniques,number of surgical interventions,modified Clavien-Dindo complications,follow-up,and mortality,if ***:Forty patients were included in the *** median age was 52(range 6-85)*** the total,25(62.5%)patients had a“significant”stent load;31(77.5%)had renal failure or acute kidney injury on presentation;19(47.5%)patients had sepsis at *** the patients presented with sepsis,11(57.9%)patients demonstrated a positive urine culture;and 7/11(63.6%)patients exhibited pan-resistant *** out of 40(30.0%)patients in our series developed high-grade Clavien-Dindo *** univariate analysis,sepsis at presentation(p=0.007),stent load(p=0.031),diabetes(p=0.023),positive urine culture(p=0.007),and stent indwelling time of more than 1 year(p=0.031)were found to be *** multivariate logistic regression analysis,sepsis at presentation(p=0.017)and positive urine culture(p=0.016)were significant predictors for high-grade ***:It is prudent to identify specific risk factors,namely sepsis at presentation and positive urine culture to triage and optimize these patients before surgical management.

关键词： Forgotten Encrusted stent Outcome Predictor Clavien-Dindo complication

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Effects of Maxingloushi decoction on immune inflammation and programmed death markers in mice with chronic obstructive pulmonary disease

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World Journal of Emergency Medicine 2022年第1期13卷 40-45页

作者： Li Li Jun Yan Lin-qin Ma Wei Bi Cai-jun Wu Emergency Department Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China institute of sepsis Beijing University of Chinese MedicineBeijing 100029China

BACKGROUND: To investigate effects of Maxingloushi decoction on lung inflammation and programmed death markers(programmed death-1 [PD-1], programmed death-ligand 1 [PD-L1]) in the lung tissue, peripheral blood, and bronchoalveolar lavage fl uid(BLF) in a mouse model of chronic obstructive pulmonary disease(COPD).METHODS: Thirty-six mature male BALB/C mice were randomly divided into normal group(group A, n=6), COPD model group(group B, n=10), Maxingloushi decoction + COPD group(group C, n=10), and PD-1 inhibitor + COPD group(group D, n=10). The COPD model was established by smoke inhalation combined with lipopolysaccharide(LPS). Levels of PD-1 and PD-L1 in plasma and BLF were measured by enzyme-linked immunosorbent assay(ELISA). Histopathological techniques were used to semi-quantitatively analyze the immuno-fluorescence optical density(IOD) value of the lung tissue. RESULTS: In plasma and BLF, the expression of PD-1 in the group B was higher than that in the group A, and the expression of PD-L1 was lower than that in the group A. The expression of PD-1 and PD-L1 in the lung tissue was normalized in the group C in comparison with the group B(P<0.05) and the group D(P<0.05), and infl ammatory cell infiltration in the lung tissue was also ***: These findings reveal that COPD causes an immune imbalance in the peripheral blood and lung tissue, and that both Maxingloushi decoction and PD-1 inhibitor treatment can mitigate lung inflammation in COPD by reducing PD-1 expression and increasing PD-L1 expression. The treatment effect of Maxingloushi decoction may be superior to that of PD-1 inhibitor.

关键词： Chronic obstructive pulmonary disease Programmed death-1 Programmed death-ligand 1 Mice Immune Maxingloushi decoction

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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(Psepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

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Predictive role of interleukin-6 and CAT score in mechanical ventilation in patients with chronic obstructive pulmonary disease at the acute exacerbation stage in the emergency department

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World Journal of Emergency Medicine 2020年第2期11卷 93-96页

作者： Wei Bi Yan Sun Lin-qin Ma Cai-jun Wu Department of Emergency Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China institute of sepsis Beijing University of Chinese MedicineBeijing 100700China Department of Emergency Sanhedongshan HospitalHebei 065200China

BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exacerbation stage in the emergency department(ED).METHODS:For a one-year period,among adult patients in the ED who met the criteria of acute exacerbation of COPD,158 who received MV within 48 hours after admission were compared to 294 who didn't require MV within the same period after ***-6 level and CAT score were compared between the two *** predicted value of IL-6 and CAT score was assessed by logistic regression analysis and a receiver operating characteristic(ROC)***:The IL-6 and CAT scores in the 158 MV patients were much higher than those ***-6 and CAT scores were independent predictors of MV within 48 hours using logistic regression analysis(IL-6:odds ratio[OR]1.053,95%confidence interval[CI]1.039–1.067,P<0.001;CAT score:OR 1.122,95%CI 1.086–1.159,P<0.001).The combination of IL-6 and CAT scores(area under ROC curve[AUC]0.826,95%CI 0.786–0.866,P<0.001)improved the accuracy of predicting MV within 48 hours when compared with IL-6(AUC 0.752,95%CI 0.703–0.800,P<0.001)and CAT scores alone(AUC 0.739,95%CI 0.692–0.786,P<0.001).The sensitivity and specificity were 69.6%,74.1%,75.32%and 63.6%,***:The combined of IL-6 and CAT scores is useful for evaluating the risk of COPD patients at acute exacerbation in ED,and can provide a predictive value for MV or not within 48 hours.

关键词： Interleukin-6 Chronic obstructive pulmonary disease(COPD) COPD assessment test Risk stratifi cation Receive operating characteristic curve

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Investigating computational models for diagnosis and prognosis of sepsis based on clinical parameters: Opportunities, challenges, and future research directions

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Journal of Intensive Medicine 2024年第4期4卷 468-477页

作者： Jyotirmoy Gupta Amit Kumar Majumder Diganta Sengupta Mahamuda Sultana Suman Bhattacharya Department of Computer Science and Engineering(IOTCSBT) Future Institute of TechnologyKolkataWest BengalIndia Department of Electronics and Communications Engineering Future Institute of TechnologyKolkataWest BengalIndia Department of Computer Science and Engineering Heritage Institute of TechnologyKolkataWest BengalIndia Department of Computer Science and Engineering Guru Nanak Institute of TechnologyKolkataWest BengalIndia

This study investigates the use of computational frameworks for *** consider two dimensions for investi-gation-early diagnosis of sepsis(EDS)and mortality prediction rate for sepsis patients(MPS).We concentrate on the clinical parameters on which sepsis diagnosis and prognosis are currently done,including customized treatment plans based on historical data of the *** identify the most notable literature that uses com-putational models to address EDS and MPS based on those clinical *** addition to the review of the computational models built upon the clinical parameters,we also provide details regarding the popular publicly available data *** provide brief reviews for each model in terms of prior art and present an analysis of their results,as claimed by the respective *** respect to the use of machine learning models,we have provided avenues for model analysis in terms of model selection,model validation,model interpretation,and model *** further present the challenges and limitations of the use of computational models,providing future research *** study intends to serve as a benchmark for first-hand impressions on the use of computational models for EDS and MPS of sepsis,along with the details regarding which model has been the most promising to *** have provided details regarding all the ML models that have been used to date for EDS and MPS of sepsis.

关键词： sepsis Computing methodologies Early prediction of sepsis Mortality prediction of sepsis Machine learning Artificial intelligence

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Prosthetic venous valves for chronic venous insufficiency:Advancements and future design directions

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Medicine in Novel Technology and Devices 2024年第1期21卷 10-22页

作者： Qiushuo Zong Jing Liu Yunfei Chen Yuanyuan Kong Yiping Dang Zhihong Wang Department of Vascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China institute of Transplant Medicine Nankai University School of MedicineTianjin300071China

With the serious aging population and lifestyle changes,chronic venous insufficiency accounts for approximately 25.95%of the population,which may lead to lower limb edema and leg heaviness,as well as severe infections of skin ulcers that can result in sepsis and necessitate *** treatment and other supportive measures can only slow the disease's progression but are unable to drastically reverse it;surgical interventions are rarely used due to the high risk of catastrophic postoperative *** one of the most promising minimally invasive therapies,percutaneous prosthetic valve replacement has emerged in light of this situation,providing novel alternatives for patients with deep venous valve *** reviewed the historical prosthetic venous valve designs,including their structure and materials,animal evaluation models,and assessment *** the basis of the findings from in vitro tests,animal studies,and clinical trials,we summarized the major challenges and potential solutions for the development of advanced prosthetic venous valves.

关键词： Prosthetic venous valves Interventional venous valves Deep venous valve insufficiency Deep venous valve reflux Valve leaflets Valve design

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CD200Rhigghh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells

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Cellular & Molecular Immunology 2024年第4期21卷 349-361页

作者： Ye Seon Kim Yu Sun Jeong Geon Ho Bae Ji Hyeon Kang Mingyu Lee Brian A.Zabel Yoe-Sik Bae Department of Biological Sciences Sungkyunkwan UniversitySuwon16419Republic of Korea Department of Health Science and Technology SAIHSTSungkyunkwan UniversitySeoul06351Republic of Korea Palo Alto Veterans institute for Research Veterans Affairs HospitalPalo AltoCA94304USA

Distinct neutrophil populations arise during certain pathological *** generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain *** this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))*** to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-α*** soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) *** administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased *** analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection *** together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.

关键词： sepsis Neutrophils CD200R Autophagy IGF-1 Regulatory T cells

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Angioinvasive mucormycosis in burn intensive care units:A case report and review of literature

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World Journal of Critical Care Medicine 2024年第1期13卷 76-84页

作者： Atul Parashar Chandra Singh Plastic Surgery Post Graduate Institute of Medical Education and ResearchChandigarh 160012India

BACKGROUND Mucormycosis is a rare,rapidly progressive and often fatal fungal *** rarity of the condition lends itself to unfamiliarity,delayed treatment,and poor *** of fungal infections early enough to enable appropriate treatment occurs in less than half of affected *** SUMMARY An 11-year-old girl with a history of 15%total body surface area scald burns involving both lower limbs progressed to develop angioinvasive *** further led to a thrombosis of the right external iliac artery and vein and rapidly progressive necrosis of surrounding soft *** also had dextrocardia and patent foramen ovale.A right hip disarticulation and serial aggressive debridements were performed but she went on to develop systemic sepsis with multisystem involvement and succumbed to the *** revealed mucor species with extensive vascular *** This case highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are signs of fulminant wound infection.

关键词： Angioinvasiveness Mucormycosis Burn sepsis Femoral artery thrombosis Case report

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Clinical characteristics of patients with Haff disease after eating crayfish

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World Journal of Emergency Medicine 2019年第3期10卷 156-159页

作者： Cai-jun Wu Hai-jiang Zhou Wei Gu Department of Emergency Medicine Dongzhimen Hospital Institute of Sepsis Beijing University of Chinese Medicine Beijing 100700 China Department of Emergency Medicine Beijing Chao-yang Hospital Capital Medical University Beijing China Emergency Medicine Center Chuiyangliu Hospital Affi liated to Tsinghua University Beijing China

BACKGROUND: The study aimed to explore the clinical presentations, laboratory findings, treatments and prognosis of patients with Haff disease after eating crayfi sh. METHODS: Sixteen patients with Haff disease after eating crayfish were admitted to the Emergency Department of Beijing Chao-yang Hospital between June 2013 and August 2017. Clinical data was retrospectively analyzed. RESULTS: Alcohol consumption and exercise were found to be most commonly associated with the onset of rhabdomyolysis after consuming crayfi sh. Most patients were young adults and the symptoms mostly occurred within 24 hours of consumption of crayfi sh. Clinical symptoms included myalgia (100%), fatigue (87.5%), nausea (43.8%), dizziness (62.5%), chest distress (37.5%) and fever (18.8%). Also found after laboratory testing was elevations in the levels of creatine kinase (11,376±5,535 U/L), myoglobin (350±158 ng/mL), lactate dehydrogenase (6,539±3,180 U/L), alanine transaminase (174±71 U/L) and aspartate aminase (348±100 U/L). The incidence of renal dysfunction was low (6.25%), and all 16 patients had a good prognosis. CONCLUSION: Patients with Haff disease exhibited typical symptoms after consuming crayfish, and laboratory findings gave highly accurate diagnostic results. The development of rhabdomyolysis was considered to be associated with alcohol consumption and exercise, but further studies are needed to demonstrate its relationship with crayfi sh consumption. Compared with other causes of rhabdomyolysis, rhabdomyolysis after crayfi sh consumption has fewer complications and better prognosis.

关键词： Haff disease Rhabdomyolysis Crayfish

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