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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin medical research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive care unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang Department of Anesthesiology and Perioperative Medicine and Department of Intensive care unit Xijing Hospital The Fourth Military Medical University Department of Critical care Medicine Translational research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins. Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis, while providing nutrients and support for cell survival. Chaperone-mediated autophagy activity can be detected in almost all cells, including neurons. Owing to the extreme sensitivity of neurons to their environmental changes, maintaining neuronal homeostasis is critical for neuronal growth and survival. Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases. It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction. Under certain conditions, regulation of chaperone-mediated autophagy activity attenuates neurotoxicity. In this paper, we review the changes in chaperone-mediated autophagy in neurodegenerative diseases, brain injury, glioma, and autoimmune diseases. We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection

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Extracorporeal membrane oxygenation in adult patients with sepsis and septic shock: Why, how, when, and for whom

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Journal of Intensive Medicine 2024年第1期4卷 62-72页

作者： Hongling Zhang Youdong Xu Xin Huang Shunyin Yang Ruiting Li Yongran Wu Xiaojing Zou Yuan Yu You Shang Department of Critical care Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430022China Department of Intensive care unit Affiliated Lu’an HospitalAnhui Medical UniversityLu’anAnhui237000China

Sepsis and septic shock remain the leading causes of death in intensive care *** patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,necessitating extracorporeal membrane oxygenation(ECMO).However,the role of ECMO in adult patients with sepsis has not been fully *** to existing studies,ECMO may be a viable salvage therapy in carefully selected adult patients with *** choice of venovenous,venoarterial,or hybrid ECMO modes is primarily determined by the patient’s oxygenation and hemodynamics(distributive shock with preserved cardiac output,septic cardiomyopathy(left,right,or biventricular heart failure),or right ventricular failure caused by acute respiratory distress syndrome).Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails,and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of *** ECMO is indicated,the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical,particularly in an experienced ECMO ***,some special issues,such as ECMO flow,anticoagulation,and antibiotic therapy,should be noted during the management of ECMO support.

关键词： Extracorporeal membrane oxygenation Sepsis Shock Acute respiratory distress syndrome(ARDS) Septic cardiomyopathy Mod

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MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex

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Journal of Intensive Medicine 2024年第2期4卷 231-239页

作者： Junfeng Su Ying Wang Jing Xie Long Chen Xinxin Lin Jiandong Lin Xiongjian Xiao Department of General Intensive care unit The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Critical care Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Critical care Medicine National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina

Background Acute kidney injury(AKI)is a primary feature of renal complications in patients with ***(miRNA/miR)-30a is an essential regulator of cardiovascular diseases,tumors,phagocytosis,and other physical processes,but whether it participates in sepsis-induced AKI(sepsis-AKI)is *** aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in *** The classical cecal ligation and puncture(CLP)method and lipopolysaccharide(LPS)-induced Human Kidney 2(HK-2)cells were used to establish in vivo and in vitro sepsis-AKI *** pathogen-free and mature male Sprague-Dawley(SD)rats,aged 6–8 weeks(weight 200–250 g),were randomly divided into five-time phase *** resuscitation with 30 mL/kg 37°C saline was administered after the operation,without ***-fixed,paraffin-embedded kidney sections were stained with hematoxylin and *** rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent ***-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors,and compared with untreated normal ***,protein,and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blot,and cell counting kit-8 methods.A Dual-Luciferase Assay Kit(Promega)was used to measure luciferase activity 48 h after transfection with miR-30a-3p *** Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h(P<0.05).Tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were significantly increased in renal tissue 3 h after the operation in rats(P<0.05),and gradually decreased 6 h,12 h,and 24 h after *** of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment(P<0.05),and gradually decreased in HK-2 *** hour after LPS(10µg/mL)treatment,TNF-αand

关键词： MicroRNA-30a TEAD1 YAP-TEAD complex Sepsis Acute kidney injury

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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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Respiratory complications of propofol,sevoflurane,and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years:a randomized trial

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南方医科大学学报 2024年第9期44卷 1631-1636页

作者： Amir Shafa Mohammad Montasery Sedighe Shahhosseini Majid Keivanfar Asieh Maghami Mehr Mahtab Ebrahim Babaei Mohammad Jafari Department of Anesthesiology Anesthesiology and Critical care research Center Department of Pediatrics Isfahan University of Medical SciencesIsfahanIran Department of Statistics Yazd UniversityYazdIran Departments of Obstetrics and Gynecology Shahrekord University of Medical SciencesShahrekordIran

Objective To evaluate the effect of propofol,sevoflurane,and dexmedetomidine on respiratory complications inchildren undergoing fiberoptic bronchoscopy(FOB).Methods This double-blind randomized clinical trial was conductedamong 120 children aged 1 month to 3 years undergoing *** patients were randomized into 3 groups(n=40)foranesthesia induction with sevoflurane inhalation,1 mg/kg propofol,or 1μg/kg dexmedetomidine before bronchoscopy,andthe changes in hemodynamic parameters,sedation level,and respiratory complications during and after the procedure *** The patients'heart rate during bronchoscopy was significantly lower and the mean arterial blood pressuresignificantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P<0.05).Cough duringbronchoscopy did not occur in any of the cases in propofol group,while the highest frequency of cough was recorded indexmedetomidine *** incidence of laryngospasm in the propofol group(12.5%)was significantly lower than those insevoflurane and dexmedetomidine groups(30%and 32.5%,respectively)(P<0.05).Conclusion Sevoflurane and propofol aresafe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve bettersedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

关键词： fiberoptic bronchoscopy propofol sevoflurane dexmedetomidine children

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Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

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World Journal of Diabetes 2024年第5期15卷 853-866页

作者： Md Abdul Alim Al-Bari Nicholas Peake Nabil Eid Department of Pharmacy University of RajshahiRajshahi 6205Bangladesh Biosciences and Chemistry and Biomolecular research Centre Sheffield Hallam UniversitySheffield S11WBUnited Kingdom Department of Anatomy Division of Human BiologySchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor *** infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and ***[particularly type 2 DM(T2DM)]and TB have converged making their control even more *** contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive *** a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both *** are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and *** addition,autophagy may play a role in these ***,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double *** effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

关键词： Diabetes mellitus Tuberculosis Coinfections Comorbidity Drug-drug interactions Autophagy Treatment challenges

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Respiratory complications of propofol, sevoflurane, and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years: a randomized trial

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南方医科大学学报 2024年

作者： Amir Shafa Mohammad Montasery Sedighe Shahhosseini Majid Keivanfar Asieh Maghami Mehr Mahtab Ebrahim Babaei Mohammad Jafari Department of Anesthesiology Anesthesiology and Critical care research Center Department of Pediatrics Isfahan University of Medical Sciences Department of Statistics Yazd University Departments of Obstetrics and Gynecology Shahrekord University of Medical Sciences

Objective To evaluate the effect of propofol, sevoflurane, and dexmedetomidine on respiratory complications in children undergoing fiberoptic bronchoscopy(FOB). Methods This double-blind randomized clinical trial was conducted among 120 children aged 1 month to 3 years undergoing FOB. The patients were randomized into 3 groups(n=40) for anesthesia induction with sevoflurane inhalation, 1 mg/kg propofol, or 1 μg/kg dexmedetomidine before bronchoscopy, and the changes in hemodynamic parameters, sedation level, and respiratory complications during and after the procedure were assessed. Results The patients' heart rate during bronchoscopy was significantly lower and the mean arterial blood pressure significantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P<0.05). Cough during bronchoscopy did not occur in any of the cases in propofol group, while the highest frequency of cough was recorded in dexmedetomidine group. The incidence of laryngospasm in the propofol group(12.5%) was significantly lower than those in sevoflurane and dexmedetomidine groups(30% and 32.5%, respectively)(P<0.05). Conclusion Sevoflurane and propofol are safe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve better sedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

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Early prediction and prevention of infected pancreatic necrosis

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World Journal of Gastroenterology 2024年第9期30卷 1005-1010页

作者： Cheng Lv Zi-Xiong Zhang Lu Ke Department of Critical care Medicine Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210000Jiangsu ProvinceChina research Institute of Critical care Medicine and Emergency Rescue Nanjing UniversityNanjing 210000Jiangsu ProvinceChina

Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal *** identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical *** the past two decades,several markers and predictive tools have been proposed and evaluated for this *** biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with *** the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better *** early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results *** together,several evidence-supported predictive markers and scoring systems are readily available for predicting ***,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral *** this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.

关键词： Acute pancreatitis Infected pancreatic necrosis Biomarker Scoring system Nutrition therapy Selective digestive decontamination Probiotics Antibiotics Immune enhancement therapy

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Prevention of ventilator-associated pneumonia with inhaled antibiotics

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World Journal of Emergency Medicine 2024年第3期15卷 165-168页

作者： Stephan Ehrmann Jie Li Intensive care Medicine INSERM CIC 1415CRICS-TriggerSep FCRIN research networkUniversity Hospital Center in ToursTours 37044France Respiratory Pathology research Center National Institute of Health and Medical ResearchTours 37000France Department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicago 60612USA

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable *** interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated *** high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

关键词： pneumonia ventilator respiratory

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