Learning curve for flexible bronchoscope-guided orotracheal intubation for anesthesiology residents: A cumulative sum analysis.

BACKGROUND: Endotracheal intubation with a flexible bronchoscope is a well-recognized airway management technique that anesthesiologists must master. Skill acquisition and knowledge must reach an appropriate level before trainees perform independent practice on patients. There are a paucity of evidence-based outcome measures of trainee competence in performing flexible bronchoscopy. The objectives of this study were to 1) construct a learning curve for flexible bronchoscope-guided orotracheal intubation for anesthesiology residents using the CUSUM method and 2) determine the number of procedures required to achieve proficiency. METHODS: This study included 12 first-year anesthesiology residents with no previous experience with flexible bronchoscopic intubation. Trainees attended theoretical and simulation training and performed flexible bronchoscope-guided orotracheal intubation in adult patients with normal airways under general anesthesia. Number of intubation attempts, intubation success rate, time to intubation, and incidence of dental and mucosal injuries were recorded. The cumulative sum (CUSUM) method was used to evaluate the learning curve of flexible bronchoscope-guided orotracheal intubation. RESULTS: Trainees performed flexible bronchoscope-guided orotracheal intubation on 364 patients. First-attempt intubation success occurred in 317 (87.1%) patients. Second-attempt intubation success occurred in 23 (6.3%) patients. Overall, the flexible bronchoscope-guided orotracheal intubation success rate was 93.4% (range, 85.3% to 100%). The mean number of orotracheal intubation procedures per trainee was 31 ± 5 (range, 23 to 40). All trainees crossed the lower decision boundary (H0) after 15.1 ± 5.6 procedures (range, 8 to 25 procedures). There was a significant decrease in median intubation time [39s (IQR: 30, 50) vs. 76s (IQR: 54, 119)] (P < 0.001) after crossing the lower decision boundary (H0) compared to before. There were no dental, mucosa, arytenoid or vocal cord trauma events associated with intubation. CONCLUSIONS: Learning curves constructed with CUSUM analysis showed that all trainees (anesthesiologist residents) included in this study achieved competence (intubation success rates ≥ 80%) in flexible bronchoscope-guided orotracheal intubation. Trainees needed to perform 15 (range, 8 to 25) procedures to achieve proficiency. There was wide variability between trainees. TRIAL REGISTRATION: Trial registration: Chinese Clinical Trial Register, ChiCTR 2000032166.

Chromosome-Level Genome Assembly of Bupleurum chinense DC Provides Insights Into the Saikosaponin Biosynthesis.

Bupleurum chinense DC is a plant widely used in Chinese traditional medicine. Saikosaponins are the major bioactive constituents of B. chinense DC. Saikosaponins biosynthesis in Bupleurum has been more intensively studied than any other metabolic processes or bioactive constituents. However, whole-genome sequencing and chromosome-level assembly for Bupleurum genus have not been reported yet. Here, we report a high-quality chromosome-level genome of B. chinense DC. through the integration of PacBio long-read sequencing, Illumina short-read sequencing, and Hi-C sequencing. The genome was phased into haplotype 0 (621.27 Mb with a contig N50 of 16.86 Mb and a scaffold N50 of 92.25 Mb) and haplotype 1 (600.48 Mb with a contig N50 of 23.90 Mb and a scaffold N50 of 102.68 Mb). A total of 45,909 and 35,805 protein-coding genes were predicted in haplotypes 0 and 1, respectively. The enrichment analyses suggested that the gene families that expanded during the evolution of B. chinense DC are involved in the biosynthesis of isoquinoline alkaloid, tyrosine, and anthocyanin. Furthermore, we analyzed the genes involved in saikosaponin biosynthesis and determined the candidate P450 and UGT genes in the third stage of saikosaponins biosynthetic, which provided new insight into the saikosaponins biosynthetic. The genomic data provide a valuable resource for future investigations of the molecular mechanisms, biological functions, and evolutionary adaptations of B. chinense DC.

AT1-receptor autoantibody exposure in utero contributes to cardiac dysfunction and increased glycolysis in fetal mice.

Exposure to adverse factors in utero may lead to adaptive changes in cardiac structure and metabolism, which increases the risk of chronic cardiovascular disease later in life. Studies showed that the angiotensin II type 1 receptor autoantibodies (AT1-AAs) are able to cross the placenta into the circulation of pregnant rodents' embryo, which adversely affects embryogenesis. However, the effects of AT1-AA exposure on the fetal heart in utero are still unknown. In this study, we investigated whether intrauterine AT1-AA exposure has adverse effects on fetal heart structure, function and metabolism. AT1-AA-positive pregnant mouse models were successfully established by passive immunity, evidenced by increased AT1-AA content. Morphological and ultrasonic results showed that the fetal mice on embryonic day 18 (E18) of AT1-AA group have loose and disordered myocardial structure, and decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), compared with control groups. The myocardium of AT1-AA group fetal mice on E18 exhibited increased expression of the key molecules in the glycolytic pathway, pyruvate and lactic acid content and ATP production, suggesting that the glycolysis rate was enhanced. Furthermore, the enhanced effect of glycolysis caused by AT1-AA is mainly through the PPARß/δ pathway. These data confirmed that fetus exposure to AT1-AA in utero developed left ventricular dysfunction, myocardial structural arrangement disorders, and enhanced glycolysis on E18. Our results support AT1-AA being a potentially harmful factor for cardiovascular disease in fetal mice.

The AT1 receptor autoantibody causes hypoglycemia in fetal rats via promoting the STT3A-GLUT1-glucose uptake axis in liver.

Blood glucose is of great importance to development and metabolic homeostasis in fetuses. Stimulation of harmful factors during gestation induces pathoglycemia. Angiotensin II type 1 receptor autoantibody (AT1-AA), a newly discovered gestational harmful factor, has been shown to induce intrauterine growth restriction in fetuses and glucose disorders in adults. However, whether and how AT1-AA influences the blood glucose level of fetuses during gestation is not yet clear. The purpose of the current study was to observe the fetal blood glucose level of AT1-AA-positive pregnant rats during late pregnancy and to determine the roles that hepatic glucose transporters play in this process. We established AT1-AA-positive pregnant rats by injecting AT1-AA into the caudal veins of rats in the 2nd trimester of gestation. Although the fetal blood glucose level in the 3rd trimester of gestation decreased, hepatic glucose uptake increased detected. Through separating membrane and cytosolic proteins, we demonstrated that both the expression and membrane transport ratio of glucose transporter 1 (GLUT1), which is responsible for glucose transport in fetal hepatocytes, were upregulated, accompanied by increased expression of N-glycosyltransferase STT3A, which contributes to the N-glycosylation of GLUT1. In vitro, we identified that AT1-AA increased glucose uptake, the expression and membrane transport ratio of GLUT1 and the expression of STT3A in HepG2 cell lines via separating membrane and cytosolic proteins and immunofluorescence, resulting in the decreased glucose content in the medium. The GLUT1 inhibitor WZB117 reversed the decreases in glucose content in the medium, the increases in glucose uptake, the increases in the expression and membrane transport ratio of GLUT1 caused by AT1-AA. The N-glycosyltransferase inhibitor NGI as well as si-STT3A reversed the AT1-AA-induced upregulation of the STT3A-GLUT1-glucose uptake effect. This study demonstrates that AT1-AA lowers the blood glucose level of fetuses via the STT3A-GLUT1-glucose uptake axis in liver.

Increased AT2R expression is induced by AT1R autoantibody via two axes, Klf-5/IRF-1 and circErbB4/miR-29a-5p, to promote VSMC migration.

Vascular remodeling can be caused by angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (AT2R) plays multiple roles in vascular remodeling through cross-talk with AT1R in the cytoplasm. Here, we aimed to explore the role and mechanism of AT2R in AT1-AA-induced vascular smooth muscle cell (VSMC) migration, which is a key event in vascular remodeling. In vitro and in vivo, we found that AT2R can promote VSMC migration in AT1-AA-induced vascular remodeling. Moreover, AT2R expression was upregulated via Klf-5/IRF-1-mediated transcriptional and circErbB4/miR-29a-5p-mediated posttranscriptional mechanisms in response to AT1-AA. Our data provide a molecular basis for AT1-AA-induced AT2R expression by transcription factors, namely, a circular RNA and a microRNA, and showed that AT2R participated in AT1-AA-induced VSMC migration during the development of vascular remodeling. AT2R may be a potential target for the treatment of AT1-AA-induced vascular diseases.

Angiotensin II inhibits apoptosis of mouse aortic smooth muscle cells through regulating the circNRG-1/miR-193b-5p/NRG-1 axis.

Angiotensin II (Ang II) is known to promote proliferation of vascular smooth muscle cells (VSMCs) in vascular remodeling, but whether it has an anti-apoptotic effect needs to be explored. Neuregulin-1 (NRG-1) as a member of the epidermal growth factor family was reported to suppress the proliferation of VSMCs by activating ErbB receptors, and therefore we hypothesized that there might be a cross talk between the anti-apoptotic effect of Ang II and the anti-proliferative effect of NRG-1 in VSMCs. The aim of the present study was to observe the expression and role of NRG-1 underlying the inhibitory effect of Ang II on apoptosis of mouse aortic smooth muscle cells (MASMCs). It was found that NRG-1 expression was down-regulated via the circNRG-1/miR-193b-5p-mediated post-transcriptional mechanism in response to Ang II. In addition, NRG-1 overexpression reversed the inhibitory effect of Ang II on apoptosis in MASMCs. Our data may provide a molecular basis for further understanding the mechanism of Ang II in suppressing the apoptosis of MASMCs by decreasing NRG-1 expression at circular RNA and micro RNA levels. The circNRG-1/miR-193b-5p/NRG-1 axis may prove to be a potential target for Ang II to inhibit the apoptosis of VSMCs and lead to vascular remodeling.

Hyperinsulinemia precedes insulin resistance in offspring rats exposed to angiotensin II type 1 autoantibody in utero.

OBJECTIVE: Insulin resistance is highly associated with an adverse intrauterine environment. We previously reported that fetal rats exposed to angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA) displayed increased susceptibility to metabolic diseases during middle age. However, the timing of the onset of insulin resistance remains unknown. In this study, we examined the offspring of AT1-AA-positive rats, tracking the development of insulin resistance. METHODS: Pregnant rats were intravenously injected with AT1-AA. Afterwards, we collected serum samples and liver tissues of the offspring at various stages, including gestation day 18, 3 weeks (weaning period), 18 weeks (young adulthood), and 48 weeks (middle age) after birth. RESULTS: Compared with saline control group, hepatic vacuolar degeneration was visible in AT1-AA offspring rats as early as 3 weeks; hyperinsulinemia and impaired glucose tolerance occurred at 18 weeks of age, however, insulin resistance was not observed until 48 weeks. At 18 weeks we detected suppressed protein levels of insulin receptor (IR) but increased levels of IR substrate 1 (IRS1) in the liver of AT1-AA group rats. Interestingly, both IR and IRS1/2 were significantly decreased at 48 weeks. Liver proteomic analysis indicated that the differences in protein expression between the AT1-AA and control rats became more pronounced with age, particularly in terms of mitochondrial energy metabolism. CONCLUSION: Rats exposed to AT1-AA in utero developed hyperinsulinemia from young adulthood which subsequently progressed to insulin resistance, and was linked with abnormal hepatic structure and impaired IR signaling. Additionally, dysregulation of energy metabolism may play a fundamental role in predisposing offspring to insulin resistance.

The mechanisms behind decreased internalization of angiotensin II type 1 receptor.

The internalization of angiotensin II type 1 receptor (AT1R) plays an important role in maintaining cardiovascular homeostasis. Decreased receptor internalization is closely related to cardiovascular diseases induced by the abnormal activation of AT1R, such as hypertension. However, the mechanism behind reduced AT1R internalization is not fully understood. This review focuses on four parts of the receptor internalization process (the combination of agonists and receptors, receptor phosphorylation, endocytosis, and recycling) and summarizes the possible mechanisms by which AT1R internalization is reduced based on these four parts of the process. (1) The agonist has a large molecular weight or a stronger ability to hydrolyze phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5) P2), which can increase the consumption of PtdIns (4,5) P2. (2) AT1R phosphorylation is weakened because of an abnormal function of phosphorylated kinase or changes in phospho-barcoding and GPCR-ß-arrestin complex conformation. (3) The abnormal formation of vesicles or AT1R heterodimers with fewer endocytic receptors results in less AT1R endocytosis. (4) The enhanced activity and upregulated expression of small GTP-binding protein 4 (Rab4) and 11 (Rab11), which regulate receptor recycling, and phosphatidylinositol 3-kinase increase AT1R recycling. In addition, lower expression of AT1R-associated protein (ATRAP) or higher expression of AT1R-associated protein 1 (ARAP1) can reduce receptor internalization.

Treating ovarian cysts with Chinese herbs: a case report.

We report the case of a female patient suffering from continuous lower abdominal distending pain from an ovarian cyst for 1 year. The sonography taken on February 12, 2008 showed on the right ovary in the frontal position a cystic mass of 43.0 x 22.0 x 45.0 mm, which was found with an intact, regular, and thin membrane and a uniform echo without blood flow. The acoustic density of the sac fluid was transparent. Pelvic fluid collection with a depth of 10 mm existed as a liquid dark area around the uterus. A simple formula of Chinese herbs, Penyan Kang (formula for treating pelvic inflammation), was orally administered to the patient for 90 days. On the 6th return visit on May 10, 2008, the patient said that all the symptoms reported during the first visit had disappeared. The sonography taken on May 27, 2008 showed that the ovarian cyst on the right side had disappeared and that no abnormality was present. No side-effect of the treatment was reported.