A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. OBJECTIVE: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. CONCLUSIONS: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

[Progress on the mechanism and treatment of Parkinson's disease-related pathological pain].

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.

Structure-Guided Designing Pre-Organization in Bivalent Aptamers.

Multivalent interaction is often used in molecular design and leads to engineered multivalent ligands with increased binding avidities toward target molecules. The resulting binding avidity relies critically on the rigid scaffold that joins multiple ligands as the scaffold controls the relative spatial positions and orientations toward target molecules. Currently, no general design rules exist to construct a simple and rigid DNA scaffold for properly joining multiple ligands. Herein, we report a crystal structure-guided strategy for the rational design of a rigid bivalent aptamer with precise control over spatial separation and orientation. Such a pre-organization allows the two aptamer moieties simultaneously to bind to the target protein at their native conformations. The bivalent aptamer binding has been extensively characterized, and an enhanced binding has been clearly observed. This strategy, we believe, could potentially be generally applicable to design multivalent aptamers.

Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation.

BACKGROUND: A Western diet is a risk factor for the development of inflammatory bowel disease (IBD). High levels of fecal deoxycholic acid (DCA) in response to a Western diet contribute to bowel inflammatory injury. However, the mechanism of DCA in the natural course of IBD development remains unanswered. AIMS: The aim of this study is to investigate the effect of DCA on the induction of gut dysbiosis and its roles in the development of intestinal inflammation. METHODS: Wild-type C57BL/6J mice were fed an AIN-93G diet, either supplemented with or without 0.2% DCA, and killed at 24 weeks. Distal ileum and colon tissues were assessed by histopathological analysis. Hepatic and ileal gene expression was examined by qPCR, and the gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. HPLC-MS was used for fecal bile acid quantification. RESULTS: Mice fed the DCA-supplemented diet developed focal areas of ileal and colonic inflammation, accompanied by alteration of the composition of the intestinal microbiota and accumulation of fecal bile acids. DCA-induced dysbiosis decreased the deconjugation of bile acids, and this regulation was associated with the repressed expression of target genes in the enterohepatic farnesoid X receptor-fibroblast growth factor (FXR-FGF15) axis, leading to upregulation of hepatic de novo bile acid synthesis. CONCLUSIONS: These results suggest that DCA-induced gut dysbiosis may act as a key etiologic factor in intestinal inflammation, associated with bile acid metabolic disturbance and downregulation of the FXR-FGF15 axis.

A Decoupled Unified Observation Method of Stochastic Multidimensional Vibration for Wind Tunnel Models.

Active vibration control is the most effective method for stochastic multidimensional vibration in wind tunnel tests, in which vibration monitoring is the core foundation. Vibrations are induced by the disturbances of several complex air flow instabilities under extreme test conditions with high attack angles. Here, a decoupled unified observation method is proposed in order to fully monitor stochastic multidimensional vibration. First, stochastic multidimensional vibration is explained using the Cartesian coordinate system. Then, the multidimensional vibration decoupling of the pitch plane and the yaw plane is realized according to the proposed decoupling design principle of the long cantilever sting. A unified observation method is presented, based on inertial force theory, to observe multidimensional vibration due to acceleration in each decoupling plane. Verification experiments were conducted in lab and a transonic wind tunnel, using an established real-time monitoring system. The results of lab experiments indicate that, in the frequency region of 0-120 Hz, three vibration modes of a selected stochastic vibration can be decoupled and observed through the vibration components in pitch plane and yaw plane. In addition, wind tunnel tests were carried out according to the working conditions (α = -4~10° with γ = 45°) at Ma = 0.6 and Ma = 0.7, respectively. The results show that six vibration modes of two selected stochastic vibrations can be decoupled and observed through the vibration components in pitch plane and yaw plane. The experimental results prove that stochastic vibration can be fully monitored in multiple dimensions through the vibration components in pitch plane and yaw plane using the proposed decoupled unified observation method. Therefore, these results lay the foundation for active vibration control.

Modular Reconfigurable DNA Origami: From Two-Dimensional to Three-Dimensional Structures.

DNA origami enables the manipulation of objects at nanoscale, and demonstrates unprecedented versatility for fabricating both static and dynamic nanostructures. In this work, we introduce a new strategy for transferring modular reconfigurable DNA nanostructures from two-dimensional to three-dimensional. A 2D DNA sheet could be modularized into connected parts (e.g., two, three, and four parts in this work), which can be independently transformed between two conformations with a few DNA "trigger" strands. More interestingly, the transformation of the connected 2D modules can lead to the controlled, resettable structural conversion of a 2D sheet to a 3D architecture, due to the constraints induced by the connections between the 2D modules. This new approach can provide an efficient mean for constructing programmable, higher-order, and complex DNA objects, as well as sophisticated dynamic substrates for various applications.

Multidimensional Vibration Suppression Method with Piezoelectric Control for Wind Tunnel Models.

In wind tunnel tests, the low-frequency and large-amplitude vibration of the cantilever sting result in poor test data in pitch plane and yaw plane, more seriously, even threatens the safety of wind tunnel tests. To ensure the test data quality, a multidimensional vibration suppression method is proposed to withstand the vibration from any direction, which is based on a system with stackable piezoelectric actuators and velocity feedback employing accelerometers. Firstly, the motion equation of the cantilever sting system is obtained by Hamilton's principle with the assumed mode method. Then, the multidimensional active control mechanism is qualitatively analyzed and a negative velocity feedback control algorithm combined with a root mean square (RMS) evaluation method is introduced to realize active mass and active damping effect, meanwhile, a weight modification method is performed to determine the sequence number of the stacked piezoelectric actuators and the weight of control voltages in real time. Finally, a multidimensional vibration suppression system was established and verification experiments were carried out in lab and a transonic wind tunnel. The results of lab experiments indicate that the damping ratio of the system is improved more than 4.3 times and the spectrum analyses show reductions of more than 23 dB. In addition, wind tunnel test results have shown that for the working conditions (α = -4~10° with γ = 0° or α = -4~10° with γ = 45°) respectively at 0.6 Ma and 0.7 Ma, the remainder vibration is less than 1.53 g, which proves that the multidimensional vibration suppression method has the ability to resist vibration from any direction to ensure the smooth process of wind tunnel tests.

Rational Design of pH-Responsive DNA Motifs with General Sequence Compatibility.

Reconfigurable molecular events are key to molecular machines. In response to external cues, molecular machines rearrange/change their structures to perform certain functions. Such machines exist in nature, for example cell surface receptors, and have been artificially engineered. To be able to build sophisticated and efficient molecular machines for an increasing range of applications, constant efforts have been devoted to developing new mechanisms of controllable structural reconfiguration. Herein, we report a general design principle for pH-responsive DNA motifs for general DNA sequences (not limited to triplex or i-motif forming sequences). We have thoroughly characterized such DNA motifs by polyacrylamide gel electrophoresis (PAGE) and fluorescence spectroscopy and demonstrated their applications in dynamic DNA nanotechnology. We expect that it will greatly facilitate the development of DNA nanomachines, biosensing/bioimaging, drug delivery, etc.

Cooperative Multifunctional Catalysts for Nitrone Synthesis: Platinum Nanoclusters in Amine-Functionalized Metal-Organic Frameworks.

Nitrones are key intermediates in organic synthesis and the pharmaceutical industry. The heterogeneous synthesis of nitrones with multifunctional catalysts is extremely attractive but rarely explored. Herein, we report ultrasmall platinum nanoclusters (PtNCs) encapsulated in amine-functionalized Zr metal-organic framework (MOF), UiO-66-NH2 (Pt@UiO-66-NH2 ) as a multifunctional catalyst in the one-pot tandem synthesis of nitrones. By virtue of the cooperative interplay among the selective hydrogenation activity provided by the ultrasmall PtNCs and Lewis acidity/basicity/nanoconfinement endowed by UiO-66-NH2 , Pt@UiO-66-NH2 exhibits remarkable activity and selectivity, in comparison to Pt/carbon, Pt@UiO-66, and Pd@UiO-66-NH2 . Pt@UiO-66-NH2 also outperforms Pt nanoparticles supported on the external surface of the same MOF (Pt/UiO-66-NH2 ). To our knowledge, this work demonstrates the first examples of one-pot synthesis of nitrones using recyclable multifunctional heterogeneous catalysts.

SNP discovery and genotyping using restriction-site-associated DNA sequencing in chickens.

Single nucleotide polymorphisms (SNPs) are essential to the understanding of population genetic variation and diversity. Here, we performed restriction-site-associated DNA sequencing (RAD-seq) on 72 individuals from 13 Chinese indigenous and three introduced chicken breeds. A total of 620 million reads were obtained using an Illumina Hiseq2000 sequencer. An average of 75,587 SNPs were identified from each individual. Further filtering strictly validated 28,895 SNPs candidates for all populations. When compared with the NCBI dbSNP (chicken_9031), 15,404 SNPs were new discoveries. In this study, RAD-seq was performed for the first time on chickens, implicating the remarkable effectiveness and potential applications on genetic analysis and breeding technique for whole-genome selection in chicken and other agricultural animals.

[The effects of DNA methylation on the homeostasis in vascular diseases].

Homeostasis is fundamental to maintain normal physiological functions in our body. Internal and external physical, chemical and biologial changes can cause dysregulation of vascular homeostasis, which is closely associated with the homeostasis of oxygen supply, blood transportation and lipid metabolism. Subsequent epigenetic modifications are able to lead to abnormal structures and function of vessels. DNA methylation has been shown to play a vital role in the development of vascular diseases. In addition, 5-hydroxymethylcytosine (5hmC) and N(6)-methyladenine (m(6)A), as new epigenetic modifications, provide additional clues for vascular diseases. In this review, we summarize the effects of DNA methylation on the homeostasis dysregulation in the vascular diseases.

PhI(OCOCF3)2-mediated intramolecular oxidative N-N bond formation: metal-free synthesis of 1,2,4-triazolo[1,5-a]pyridines.

The biologically important 1,2,4-triazolo[1,5-a]pyridines were readily synthesized from N-(pyridin-2-yl)benzimidamides via phenyliodine bis(trifluoroacetate)-mediated intramolecular annulation. This novel strategy allows for the convenient construction of a 1,2,4-triazolo[1,5-a]pyridine skeleton through direct metal-free oxidative N-N bond formation, featuring a short reaction time and high reaction yields.

Circular Single-Stranded DNA: Discovery, Biological Effects, and Applications.

The field of nucleic acid therapeutics has witnessed a significant surge in recent times, as evidenced by the increasing number of approved genetic drugs. However, current platform technologies containing plasmids, lipid nanoparticle-mRNAs, and adeno-associated virus vectors encounter various limitations and challenges. Thus, we are devoted to finding a novel nucleic acid vector and have directed our efforts toward investigating circular single-stranded DNA (CssDNA), an ancient form of nucleic acid. CssDNAs are ubiquitous, but generally ignored. Accumulating evidence suggests that CssDNAs possess exceptional properties as nucleic acid vectors, exhibiting great potential for clinical applications in genetic disorders, gene editing, and immune cell therapy. Here, we comprehensively review the discovery and biological effects of CssDNAs as well as their applications in the field of biomedical research for the first time. Undoubtedly, as an ancient form of DNA, CssDNA holds immense potential and promises novel insights for biomedical research.

Pathological pain: Non-motor manifestations in Parkinson disease and its treatment.

In addition to motor symptoms, non-motor manifestations of Parkinson's disease (PD), i.e. pain, depression, sleep disturbance, and autonomic disorders, have received increasing attention. As one of the non-motor symptoms, pain has a high prevalence and is considered an early pre-motor symptom in the development of PD. In relation to pathological pain and its management in PD, particularly in the early stages, it is hypothesized that the loss of dopaminergic neurons causes a functional deficit in supraspinal structures, leading to an imbalance in endogenous descending modulation. Deficits in dopaminergic-dependent pathways also affect non-dopaminergic neurotransmitter systems that contribute to the pathological processing of nociceptive input, the integration, and modulation of pain in PD. This review examines the onset and progression of pain in PD, with a particular focus on alterations in the central modulation of nociception. The discussion highlights the importance of abnormal endogenous descending facilitation and inhibition in PD pain, which may provide potential clues to a better understanding of the nature of pathological pain and its effective clinical management.

A pharmacovigilance study on antibody-drug conjugate (ADC)-related neurotoxicity based on the FDA adverse event reporting system (FAERS).

Background: Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents that use monoclonal antibodies to specifically recognize tumour cell surface antigens. However, off-target effects may lead to severe adverse events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse Event Reporting System (FAERS) database. Research design and methods: Data were extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the clinical characteristics of ADC-related neurological adverse events (AEs). We used the reporting odds ratio (ROR) and proportional reporting ratio (PRR) for the disproportionality analysis to evaluate the potential association between AEs and ADCs. Results: A total of 562 cases of neurological AEs were attributed to ADCs. The median age was 65 years old [(Min; Max) = 3; 92]. Neurotoxic signals were detected in patients receiving brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan. The payloads of brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and trastuzumab emtansine were microtubule polymerization inhibitors, which are more likely to develop neurotoxicity. We also found that brentuximab vedotin- and gemtuzumab ozogamicin-related neurological AEs were more likely to result in serious outcomes. The eight most common ADC-related nervous system AE signals were peripheral neuropathy [ROR (95% CI) = 16.98 (14.94-19.30), PRR (95% CI) = 16.0 (14.21-18.09)], cerebral haemorrhage [ROR (95% CI) = 9.45 (7.01-12.73), PRR (95% CI) = 9.32 (6.95-12.50)], peripheral sensory neuropathy [ROR (95% CI) = 47.87 (33.13-69.19), PRR (95% CI) = 47.43 (32.93-68.30)], polyneuropathy [ROR (95% CI) = 26.01 (18.61-36.33), PRR (95% CI) = 25.75 (18.50-35.86)], encephalopathy [ROR (95% CI) = 5.16 (3.32-8.01), PRR (95% CI) = 5.14 (3.32-7.96)], progressive multifocal leukoencephalopathy [ROR (95% CI) = 22.67 (14.05-36.58), PRR (95% CI) = 22.52 (14.01-36.21)], taste disorder [ROR (95% CI) = 26.09 (15.92-42.76), PRR (95% CI) = 25.78 (15.83-42.00)], and guillain barrier syndrome [ROR (95% CI) = 17.844 (10.11-31.51), PRR (95% CI) = 17.79 (10.09-31.35)]. The mortality rate appeared to be relatively high concomitantly with AEs in the central nervous system. Conclusion: ADCs may increase the risk of neurotoxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADC drugs, combining the FAERS data with other data sources is crucial for monitoring the neurotoxicity of ADCs. Further studies on the potential mechanisms and preventive measures for ADC-related neurotoxicity are necessary.

Antinociceptive role of the thalamic dopamine D3 receptor in descending modulation of intramuscular formalin-induced muscle nociception in a rat model of Parkinson's disease.

Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the present study, we investigated the role of the dopamine D3 receptor in the thalamic mediodorsal (MD) and ventromedial (VM) nuclei mediated descending control of nociception and intramuscular (i.m.) 2.5% formalin-induced persistent muscle nociception. Paw withdrawal reflexes were measured in naive rats and rats subjected to PD induced by unilateral microinjection of 6 µg 6-OHDA into the rat striatum. Formalin-induced muscle nociception in phase 1, inter-phase, and phase 2 was significantly greater in PD rats compared to naive and vehicle-treated rats (P ˂ 0.001). PD rats exhibited bilaterally mechanical hyperalgesia and heat hypoalgesia in formalin-induced muscle nociception. Microinjection of SK609, a dopamine D3 receptor agonist, at various doses (2.5-7.5 nmol/0.5 µl) into the thalamic VM nucleus dose-dependently prolonged heat-evoked paw withdrawal latencies in both naive and PD rats. Administration of SK609 to either the MD or VM nuclei had no effect on noxious mechanically evoked paw withdrawal reflexes. Pre-treatment of the thalamic MD nucleus with SK609 significantly attenuated formalin-induced nociception, and reversed mechanical hyperalgesia, but not heat hypoalgesia. Pre-treatment of the thalamic VM nucleus with SK609 inhibited formalin-induced nociception in the late phase of phase 2 (30-75 min) and heat hypoalgesia, but not mechanical hyperalgesia (P < 0.05). It is suggested that the dopamine D3 receptors in the thalamus play an antinociceptive role in the descending modulation of nociception. Activation of D3 receptors within the thalamic MD and VM nuclei attenuates descending facilitation and enhances descending inhibition in rats during PD.

Comparison of intranasal dexmedetomidine alone and dexmedetomidine-chloral hydrate combination sedation for electroencephalography in children: A large retrospective cohort study and propensity score-matched analysis.

Aim: To compare the safety and efficacy of intranasal high-dose dexmedetomidine (DEX) versus a combination of intranasal low-dose dexmedetomidine and oral chloral hydrate (DEX-CH) sedation during electroencephalography (EEG) in children. Methods: Unadjusted analysis, 1:1 propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used to compare the sedation success rate, adverse effects, onset time, and recovery time of these two sedation methods for 6967 children who underwent EEG. Results: A total of 6967 children were enrolled in this study, of whom 846 (12.1 %) underwent DEX intranasal sedation while 6121 (87.9 %) received DEX-CH sedation. No significant differences were observed in the sedation success rate with the first dose between the two groups [824 (97.4 %) for DEX vs. 5971 (97.6 %) for DEX-CH; RR 0.99; 95 % CI, 0.98-1.01; P = 0.79]. Similarly, there were no notable disparities in the incidence of adverse events [16 (1.9 %) for DEX vs. 101 (1.7 %) for DEX-CH; RR 1.15; 95 % CI, 0.68-1.93; P = 0.32]. However, intranasal DEX sedation compared with DEX-CH sedation was associated with lower vomiting [0 vs. 95(1.6 %); RR 0.04; 95 % CI, 0.02-0.6; P = 0.02] or more bradycardia [13(1.5 %) vs. 2(0.03 %); RR 47.03; 95 % CI, 10.63-208.04; P < 0.001]. Multivariate analysis using PSM and IPTW analysis yielded similar results. Conclusion: Both methods for EEG had high sedation success rate and low incidence of adverse events. High-dose intranasal DEX was more likely to induce bradycardia and had a shorter recovery time than the DEX-CH sedation, which was more likely to induce vomiting.

Risk of Hematologic Malignancies in Patients with Inflammatory Bowel Disease: A Meta-Analysis of Cohort Studies.

Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions: The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database.

BACKGROUND: Bevacizumab is used for the treatment of advanced malignant tumors; it acts by inhibiting angiogenesis. This study aimed to examine adverse events (AEs) of bevacizumab, especially hemorrhage, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to analyze the AEs of bevacizumab using FAERS registration data from January 2004 to September 2022. Clinical information regarding hemorrhagic signals was further analyzed. RESULTS: The number of bevacizumab-associated AE reports was 96,477. Our study found that 892 significant preferred terms (PTs) were spread throughout 25 organ systems. The system organ classes (SOCs) focus on general disorders, administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. A total of 2,847 bevacizumab-related hemorrhage cases were reported, and 37 hemorrhagic signals were identified. Hemorrhagic signals were focused on SOC levels in vascular, gastrointestinal, and nervous system disorders. Colorectal, lung, and breast cancers are the three most common malignancies associated with BV-induced hemorrhage. CONCLUSION: The AE report from the present study confirms the majority of label information for bevacizumab, while also identifying new AEs. In addition, this was a large descriptive study of bevacizumab-induced hemorrhage.

Airway management with Hi-flow nasal cannula oxygen in children with severe laryngeal obstruction.

BACKGROUND: The aim of this study was to report our initial experience in airway management in young children with severe laryngeal obstruction. Hi-flow nasal cannula oxygen (HFNO) with spontaneous respiration was used as a new airway management strategy in young children undergoing suspension laryngoscopic surgery. METHODS: Children aged between 1 day and 24 months scheduled for suspension laryngoscopy were retrospectively studied. The data collected included the patients' age, gender, American Society of Anaesthesiologists physical status classification, comorbidities, preoperative physiological status, methods of induction and maintenance of anesthesia, course of the disease and surgical options, lowest oxygen saturation recorded, transcutaneous CO2, duration of operation, and patients' need for rescue methods. RESULTS: A total of 38 patients successfully underwent suspension laryngoscopy under HFNO with spontaneous respiration. 19 patients were less than 1 year old (7 neonates), while the other half were less than or equal to 2 years old. The median [IQR (range)] lowest oxygen saturation recorded during the operation was 98 [93-99 (91-99)] %. The median [IQR (range)] duration of HFNO with spontaneous respiration was 65 [45-100 (30-200)] minutes. The median [IQR (range)] PCO2/PtcCO2 at the end of the spontaneous ventilation period was 54 [48-63 (39-70)] mmHg, which was the same as the preoperative PCO2 despite a long operation time. CONCLUSIONS: HFNO with spontaneous respiration emerged as a new airway management strategy in young children with severe laryngeal obstruction that was beneficial in maintaining oxygenation and was superior to transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in terms of the rising rate of PCO2 in these patients, thereby prolonging the safety time of the operation.