Effects of a single dose of rocuronium in patients with different body fat percentages: A randomised controlled trial.

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.

A mixed-reality stimulator for lumbar puncture training: a pilot study.

BACKGROUND: The simulation is one of the basic methods of medical education, which is often used for procedural skills training. However, the existing simulator lacks internal anatomical landmarks. The study developed a mixed-reality stimulator and evaluated its usability and feasibility in lumbar puncture training. METHODS: The study recruited 40 subjects, including medical students, residents and faulty with varied levels of experience. Before training, participants completed the questionnaire about the basic information and watched a presentation about mixed reality. After practicing on mixed-reality stimulator, which provided internal anatomical structure, the examination was carried out and the results were documented. At the end of the training, trainees completed a survey of MR technology. RESULTS: In this study, participants generally believed that the MR technology was very realistic (90%), and that the presentation of internal anatomy could help the operation (95%). Moreover, 72.5% and 75%, respectively, strongly agreed that the MR technology promoted learning and should be used in medical training. After this training, the success rate of puncture and the puncture time were significantly improved in experienced and non-experienced participants. CONCLUSION: The existing simulator was easy to be transformed into MR simulator. This study showed the usability and feasibility of MR simulator in lumbar puncture training. As a potentially good tool to simulated medical skills training, next, MR technology would be developed and evaluated in more clinical skills teaching scenarios.

Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis.

Neutrophils are mobilized and recruited to the injured heart after myocardial infarction, and neutrophil count has been clinically implicated to be associated with coronary disease severity. Histidine decarboxylase (HDC) has been implicated in regulating reactive oxidative species (ROS) and the differentiation of myeloid cells. However, the effect of HDC on neutrophils after myocardial infarction remains unclear. Here, we found that neutrophils were disorderly recruited into the ischemic injured area of the myocardium of Hdc deficiency (Hdc -/-) mice. Moreover, Hdc deficiency led to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps (NETs) production in neutrophils. Hdc -/- mouse-derived NETs promoted cardiomyocyte death and cardiac fibroblast proliferation/migration. Furthermore, protein arginine methyltransferase 1 (PRMT1) was increased in Hdc -/- mouse-derived neutrophils but decreased with exogenous histamine treatment. Its expression could be rescued by blocking histamine receptor 1 (H1R), inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable (SWI/SNF) chromatin remodeling complex. Accordingly, histamine or MS023 treatment could decrease ROS and NETs ex vivo, and ameliorated cardiac function and fibrosis, along with the reduced NETs in plasma in vivo. Together, our findings unveil the role of HDC in NETosis by histamine-H1R-ATP-SWI/SNF-PRMT1-ROS signaling and provide new biomarkers and targets for identifying and tuning the detrimental immune state in cardiovascular disease.

Histamine deficiency delays ischaemic skeletal muscle regeneration via inducing aberrant inflammatory responses and repressing myoblast proliferation.

Histidine decarboxylase (HDC) catalyses the formation of histamine from L-histidine. Histamine is a biogenic amine involved in many physiological and pathological processes, but its role in the regeneration of skeletal muscles has not been thoroughly clarified. Here, using a murine model of hindlimb ischaemia, we show that histamine deficiency in Hdc knockout (Hdc-/- ) mice significantly reduces blood perfusion and impairs muscle regeneration. Using Hdc-EGFP transgenic mice, we demonstrate that HDC is expressed predominately in CD11b+ Gr-1+ myeloid cells but not in skeletal muscles and endothelial cells. Large amounts of HDC-expressing CD11b+ myeloid cells are rapidly recruited to injured and inflamed muscles. Hdc-/- enhances inflammatory responses and inhibits macrophage differentiation. Mechanically, we demonstrate that histamine deficiency decreases IGF-1 (insulin-like growth factor 1) levels and diminishes myoblast proliferation via H3R/PI3K/AKT-dependent signalling. These results indicate a novel role for HDC-expressing CD11b+ myeloid cells and histamine in myoblast proliferation and skeletal muscle regeneration.

Excessive Neutrophil Extracellular Trap Formation Aggravates Acute Myocardial Infarction Injury in Apolipoprotein E Deficiency Mice via the ROS-Dependent Pathway.

Genetically human apolipoprotein E (APOE) ε32 is associated with a decreased risk of ischemic heart disease. ApoE deficiency in mice impairs infarct healing after myocardial infarction (MI). After the ischemic injury, a large number of neutrophils are firstly recruited into the infarct zone and then degrade dead material and promote reparative phase transformation. The role of ApoE in inflammation response in the early stage of MI remains largely unclear. In this study, we investigated the effect of ApoE deficiency on neutrophils' function and myocardial injury after myocardial infarction. By left coronary artery ligation in ApoE -/- and wild-type (WT) mice, we observed increased infarct size and neutrophil infiltration in ApoE -/- mice. Within the infarct zone, more neutrophil extracellular traps (NETs) were observed in ApoE -/- mice, while increased ex vivo NET formation was detected in ApoE -/- mouse-derived neutrophils through the NADPH oxidase-ROS-dependent pathway. Suppressing overproduced NETs reduced myocardial injury in ApoE -/- mice after ligation. In general, our findings reveal a critical role of apolipoprotein E in regulating Ly6G+ neutrophil activation and NET formation, resulting in limiting myocardial injury after myocardial infarction. In such a process, apolipoprotein E regulates NET formation via the ROS-MAPK-MSK1 pathway.

Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

Histamine is a widely distributed biogenic amine involved in the regulation of an array of biological processes. Serum histamine level is markedly elevated in the early stages of acute myocardial infarction, whereas the role it plays remains unclear. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine production, and cardiac injury is significantly aggravated in HDC knockout mice (HDC-/-), in which histamine is deficient. We also observed that autophagy was highly activated in cardiomyocytes of HDC-/- mice post acute myocardial infarction (AMI), which was abolished by compensation of exogenous histamine. The in vivo and in vitro results showed that acting through histamine 1 receptor, histamine increased miR-206 and miR-216b, which worked in concert to target to Atg13, resulting in the reduction of autophagy activation under hypoxia and AMI condition. Further study revealed that Atg13 interacted with FADD to promote the activation of caspase-8 and cell apoptosis. Taken together, these data unveil a novel intracellular signaling pathway involved in histamine regulating myocardial autophagy and apoptosis under hypoxia and AMI condition, which might help to more comprehensively evaluate the usage of histamine receptor antagonists and to develop new therapeutic targets for myocardial infarction.