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Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Neural Regeneration Research 2024年第5期19卷 1105-1111页

作者： Tao Liu Ziqian Ma Liang Liu Yilun Pei Qichao Wu Songjie Xu Yadong Liu Nan Ding Yun Guan Yan Zhang Xueming Chen department of Orthopedic surgery Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of Orthopedic surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina department of Stomatology Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of Anesthesiology and critical care medicine School of MedicineJohns Hopkins UniversityBaltimoreMDUSA department of Neurological surgery School of MedicineJohns Hopkins UniversityBaltimoreMDUSA

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord ***,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains *** the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem *** found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial *** addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1β*** results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord ***,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

关键词： BV2 conditioned medium dental pulp stem cells GSDMD microglia neuroinflammation NLRP3 pyroptosis spinal cord injury

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Bronchobiliary fistula in a patient with liver cancer

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 523-525页

作者： Yao-Xin Chen Zhi-Hua Deng Hao Zhao Bi-Ying Zhou Jing-Jing Guo Gang Zeng Jin-Xian Qian department of Respiratory and critical care medicine Suzhou Municipal Hospital Affiliated to Nanjing Medical UniversitySuzhou 215000China

Bronchobiliary fistula(BBF) is a pathologic channel between the biliary tract and bronchial tree. In general, congenital BBF is relatively rare in adult patients. There are a few case reports suggesting that BBF is mainly secondary to hepatobiliary diseases, such as biliary obstruction, tumor, surgery, or liver abscess, and liver tumor is the predominant causative factor [1]. In addition, with the increasing number of liver and biliary surgeries and interventional therapies in recent years, more cases of BBF were reported as a postoperative complication [ 2, 3 ]. In this case, we presented a patient who underwent interventional treatment for liver tumor and was treated for his respiratory symptoms but diagnosed with BBF finally. Here, we summarized the clinical features and main diagnostic procedures of the case, aiming to provide evidence for early identification and diagnosis of BBF.

关键词： biliary fistula diagnosis

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Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

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Current Medical Science 2024年第1期44卷 110-120页

作者： Chang-zhi ZHOU Xiong XIONG Wei-jun TAN Ya-fei WANG Zhen YANG Xue-ying LI Xiu-wen YANG Xiao-fan LIU Sun-feng YU Liang-chao WANG Shuang GENG department of Respiratory and critical care medicine The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China department of General surgery Wuhan Wuchang HospitalWuhan University of Science and TechnologyWuhan 430063China

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in *** study investigated the impact of Bcl-6 on asthmatic *** The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference *** surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,*** relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were *** Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these *** percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM ***-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM *** IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar *** asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 *** The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

关键词： Bcl-6 Tfh asthma airway hyper-responsiveness mouse model

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Upregulation of circ0000381 atienuates microglial/macrophage pyroptosis after spinal cord injury

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Neural Regeneration Research 2024年第6期19卷 1360-1366页

作者： Yan Zhang Wenkai Zhang Tao Liu Ziqian Ma Wenxiu Zhang Yun Guan Xueming Chen Central Laboratory Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of Orthopedics Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of Emergency medicine Aerospace Center HospitalBeijingChina department of Anesthesiology and critical care medicine Johns Hopkins University School of MedicineBaltimoreMDUSA department of Neurological surgery Johns Hopkins University School of MedicineBaltimoreMDUSA

Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to *** RNAs(circRNAs)play a role in the central nervous ***,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly *** the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal *** further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis ***,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage ***,knockdown of circ0000381 expression exacerbated microglia/macrophage ***,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord ***,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

关键词： circ0000381 inflammasome macrophage microglia miR-423-3p neuroinflammation neuroprotection NLRP3 pyroptosis RNA-Seq spinal cord injury

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Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers

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World Journal of Emergency medicine 2024年第1期15卷 3-9页

作者： Rashed Alremeithi Quincy K.Tran Megan T.Quintana Soroush Shahamatdar Ali Pourmand department of Emergency medicine George Washington University School of Medicine and Health SciencesWashington DC 20037USA department of Emergency medicine University of Maryland School of MedicineBaltimore 21201USA Program in Trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA Center for Trauma and critical care Department of Surgerythe George Washington University School of Medicine&Health SciencesWashington DC 20037USA

BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare *** there have been advances in treatment modalities,survival rates for TCA patients remain *** narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating ***:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,*** search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English *** the search,943 articles were retrieved,and two independent reviewers conducted a screening ***:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable *** were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital *** thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt *** endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic *** implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality ***-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,*** the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ***:TCA remains a signifi cant challenge for emergency medical services due to its high m

关键词： Traumatic cardiac arrest Emergency thoracotomy Resuscitative endovascular balloon occlusion of the aorta

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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan Ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang department of Pathology department of Minimally Invasive Tumor Therapies Center department of Thoracic surgery department of Oncology department of Respiratory and critical care medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy Diagnostics Co. Ltd.Xiamen 361027China

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:Of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type ***-positive NSCLC displayed higher tumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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Outcomes of early versus late irrigation and debridement of pediatric open long bone fractures

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World Journal of Orthopedics 2024年第6期15卷 539-546页

作者： Riya Savla Yen-Hong Kuo Nasim Ahmed department of surgery and Trauma Hackensack Meridian School of MedicineNutleyNJ 07110United States department of Medical Sciences Hackensack Meridian School of medicineNutleyNJ 08753United States Office of Research Administration Hackensack Meridian Health Research InstituteNutleyNJ 077110United States department of surgery Department of Trauma and Surgical Critical CareJersey Shore University Medical CenterNeptuneNJ 07754United States department of surgery Department of Trauma and Surgical Critical CareHackensack Meridian School of MedicineNutleyNJ 07110United States

BACKGROUND Open long bone fractures are a major concern for pediatric patients due to the risk of surgical site infection(SSI).Early studies have recommended irrigation and debridement of open fractures within 6 hours-8 hours for the prevention of *** to the American College of Surgeons(ACS)Best Practice Guidelines,in 2015,irrigation and debridement should be done within 24 *** To identify whether early irrigation and debridement,within 8 hours,vs late,between 8 hours and 24 hours,for pediatric open long bone fractures impacts rate of *** Using retrospective data review from the National Trauma Data Bank,Trauma Quality Improvement Project(TQIP)of *** database is own by the ACS and it is the largest database for trauma quality program in the *** matching analysis was performed for the *** There were 390 pediatric patients with open long bone fractures who were incl-uded in the *** completing propensity score matching,we had 176 patients in each category,irrigation and debridement within 8 hours and irrigation and debridement between 8 hours and 24 *** found no significant differences between each group for the rate of deep SSI which was 0.6%for patients who received surgical irrigation and debridement within 8 hours and 1.1%for those who received it after 8 hours[adjusted odd ratio(AOR):0.5,95%CI:0.268-30.909,P>0.99].For the secondary outcomes studied,in terms of length of hospital stay,patients who received irrigation and debridement within 8 hours stayed for an average of 3.5 days,and those who received it after 8 hours stayed for an average of 3 days,with no significant difference found,and there were also no sig-nificant differences found between the discharge dispositions of the *** Our findings support the recommendation for managing open long bone fractures from the ACS:Complete surgical irrigation and debridement within 24 hours.

关键词： Pediatric trauma Open tibia fracture Irrigation and debridement Timing of intervention Surgical site infection

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Knockdown of the nucleoporin Nup50 protects cells against ionizing radiation through enhancing DNA-PKcs-mediated DNA damage repair

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Radiation medicine and Protection 2024年第3期5卷 194-200页

作者： Zhijie Wan Jingwen Gu Songyun Zhao Hang Jia Tingting Liu Yuanyuan Chen Yanyong Yang department of Radiation medicine Faculty of Naval MedicineNaval Medical UniversityShanghai200433China department of Respiratory and critical care medicine the Second Naval Hospital of Southern Theater CommandSanyaHainan572000China department of Colorectal surgery Changhai HospitalNaval Medical UniversityShanghai200433China

Objective:To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective ***:The Nup50 gene was knocked down in HUVEC cells using *** formation,CCK-8,and flow cytometry were performed to determine the viability,proliferation and apoptosis of HUVEC cells treated withγ-rays,*** extent of DNA damage was evaluated by using comet assay and immu-nofluorescence staining againstγ-*** addition,we explored the role of Nup50 in DNA damage response(DDR)pathways through western blotting ***,nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 ***:Nup50 knockdown increased the cellular resistance to ionizing *** CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation(t=4.23,P<0.01).The Nup50 knockdown group also showed more survived colonies(t=10.06,P<0.001),less apoptosis rate(t=3.78,P<0.05)and less unrepaired DNA ***,Nup50 knockdown increased radiation-activated phosphorylation levels of DNA-PKcs in HUVEC ***,the nuclear and chromatin fractionation data showed that inhibiting Nup50 increased the recruitment of DNA-PKcs to chromatin after DNA ***:Our findings revealed that Nup50 knockdown promoted radioresistance in normal HUVEC cells by regulating DNA-PKcs pathway,suggesting Nup50 as a potential target for radiation protection.

关键词： damage protective p50

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Single-domain antibodies as therapeutics for solid tumor treatment

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2854-2868页

作者： Mingkai Wang Tianlei Ying Yanling Wu MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology School of Basic Medical SciencesDepartment of Pulmonary and Critical Care MedicineDepartment of Liver Surgery and TransplantationZhongshan HospitalFudan UniversityShanghai 200032China Shanghai Engineering Research Center for Synthetic Immunology Shanghai 200032China

Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic *** sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue ***,the inherent challenges associated with the animal origin of sdAbs limit their clinical *** recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their *** review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization *** addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.

关键词： Single-domain antibody Nanobody Humanization Fully human singledomain antibody Solid tumor

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Effect of high-protein peptide-based formula compared with isocaloric isonitrogenous polymeric formula in critically ill surgical patient

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World Journal of Gastrointestinal surgery 2024年第6期16卷 1765-1774页

作者： Preeda Sumritpradit Prapimporn Chattranukulchai Shantavasinkul Winai Ungpinitpong Pinit Noorit Chotip Gajaseni Division of Trauma surgery and Surgical critical care Department of SurgeryFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Division of Nutrition and Biochemical medicine Department of MedicineFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Graduate Program in Nutrition Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand department of surgery Surin HospitalSurin 32000Thailand department of surgery Chonburi HospitalChonburi 20000Thailand department of Nursing Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand

BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of *** enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to ***-based formulas have been shown to be beneficial in patients with feeding ***,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical *** To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric *** This study was a multi-center double-blind,randomized controlled *** enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d *** were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 *** residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and *** A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula *** the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard ***,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass *** body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day ***,the participants in the peptide-based formula tended to reach their caloric target faster than the standard ***

关键词： Peptide-based formula Surgical intensive care Hydrolyzed protein surgery Nutritional support

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