Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway.

Objective: To clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells. Methods: Different concentrations of Sev were used to treat glioma cells U87 and U251. Ferroptosis inducer Erastin was used to incubate glioma cells combined with Sev and ATF4 siRNA transfection treatment. CCK-8 assay and colorimetric assay were performed to analyze cell viability and Fe+ concentration, respectively. The releases of reactive oxygen species (ROS) were determined by flow cytometry analysis. Transcriptional sequencing was used to screen the differential genes affected by Sev in U251 cells. The mRNA and protein expression of ferroptosis-associated genes was detected by qRT-PCR and Western blotting. Results: Sev could suppress cell viability, increase ROS levels and Fe+ concentration, downregulate the protein expression levels of GPX4, and upregulate transferrin, ferritin, and Beclin-1 in a dose-dependent manner in U87 and U251 cells. The expression of ferroptosis and mitophagy-related gene activating transcription factor 4 (ATF4) was identified to be enhanced by Sev analyzed by transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved in ferroptosis, is a downstream gene of ATF4. Inhibition of ATF4 could interrupt the expression of CHAC1 induced by Sev in U87 and U251 cells. Ferroptosis inducer Erastin treatment obviously inhibited the cell viability, elevated the Fe2+ concentration, and promoted ROS generation in U87 and U251 cells. The protein level of ATF4 and CHAC1 was increased in Erastin-treated U87 and U251 cells. Moreover, the interruption of Sev-induced ferroptosis and CHAC1 activating induced by ATF4 suppression could be reversed by Erastin. Conclusions: In summary, this study suggested that Sev exposure-induced ferroptosis by the ATF4-CHAC1 pathway in glioma cells.

Flexible endoscopic identification and catheterization of congenital H-type tracheoesophageal fistula using a laryngeal mask.

Endoscopy for revealing the orifice of congenital H-type tracheoesophageal fistula (cTEF) is important for diagnostics and therapeutics. To facilitate the identification and catheterization of cTEF, we developed a new modified flexible endoscopy technique using a laryngeal mask with intermittent airflow. A retrospective case series study was conducted from April 2016 to July 2019 at a national regional children's medical center. Twelve infants with cTEF underwent this flexible endoscopy technique. The intermittent positive pressure airflow through laryngeal mask was able to reveal the orifice of cTEF easily in tracheal lumen. Under the visual flexible endoscope, cannulation with a 3-Fr ureteral catheter in fistula was successfully used in all cases. There were no immediate or delayed complications. This case series shows that the flexible endoscopy technique is a safe, easy, and technically efficient approach for diagnosis and cannulation of cTEF.

Inositol Alleviates Pulmonary Fibrosis by Promoting Autophagy via Inhibiting the HIF-1α-SLUG Axis in Acute Respiratory Distress Syndrome.

The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

The impact of height on the spread of spinal anesthesia and stress response in parturients undergoing caesarean section: a prospective observational study.

BACKGROUND: The spread of spinal anesthesia was influenced by many factors, and the effect of body height on spinal anesthesia is still arguable. This study aimed to explore the impact of height on the spread of spinal anesthesia and the stress response in parturients. METHODS: A total of ninety-seven parturients were allocated into two groups according to their height: the shorter group (body height was shorter than 158 cm) and taller group (body height was taller than 165 cm). Spinal anesthesia was performed with the same amount of 12 mg plain ropivacaine in mothers of different heights. The primary outcome of the study was the success or failure of the spinal anesthesia. The secondary outcomes of the study were stress response, time to T6 sensory level, the incidence of hypotension, the satisfaction of abdominal muscle relaxation and patient VAS scores. RESULTS: The rate of successful spinal anesthesia in the shorter group was significantly higher than that in the taller group (p = 0.02). The increase of maternal cortisol level in the shorter group was lower than that in the taller group at skin closure (p = 0.001). The incidence of hypotension (p = 0.013), time to T6 sensory block (p = 0.005), the quality of abdominal muscle relaxation (p <  0.001), and VAS values in stretching abdominal muscles and uterine exteriorization (p <  0.001) in the shorter group were significantly different from those in the taller group. Multivariate analysis showed that vertebral column length (p <  0.001), abdominal girth (p = 0.022), amniotic fluid index (p = 0.022) were significantly associated with successful spinal anesthesia. CONCLUSIONS: It's difficult to use a single factor to predict the spread of spinal anesthesia. Patient's vertebral column length, amniotic fluid index and abdominal girth were the high determinant factors for predicting the spread of spinal anesthesia. TRIALS REGISTRATION: ChiCTR-ROC-17012030 ( Chictr.org.cn ), registered on 18/07/2017.

The effects of ropivacaine 0.0625% and levobupivacaine 0.0625% on uterine and abdominal muscle electromyographic activity during the second stage of labor.

BACKGROUND: This study investigated the effect of ropivacaine on uterine and abdominal muscle electromyographic activity during the second stage of labor. METHODS: A total of 161 patients, including 48 patients receiving 0.0625% ropivacaine for patient-controlled epidural analgesia (PCEA), 64 patients receiving 0.0625% levobupivacaine for PCEA, and 49 patients with no PCEA completed the study. Uterine and abdominal muscle electromyographic activity was continuously recorded from the abdominal surface during the second stage of labor. Maternal demographic and clinical characteristics, maternal and neonatal outcomes, and various electromyographic parameters were recorded. RESULTS: Second stage of labor was significantly prolonged (P=0.007) for levobupivacaine compared to ropivacaine or no PCEA. The root-mean-square and duration of uterine muscle electromyographic activity was significantly lower for levobupivacaine or ropivacaine compared to no PCEA. The root-mean-square and power of abdominal muscle electromyographic activity was significantly lower for levobupivacaine compared to ropivacaine or no PCEA; the peak frequency of abdominal muscle electromyographic activity was significantly higher for ropivacaine. Visual analogue scale pain scores in patients in the levobupivacaine group or ropivacaine group decreased significantly over time compared to patients in the no PCEA group. CONCLUSIONS: In conclusion 0.0625% ropivacaine does not suppress abdominal muscle electromyographic activity during the second stage of labor. Maternal and neonatal outcomes were similar in patients receiving ropivacaine or no PCEA.

Effects of Ropivacaine in Patient-Controlled Epidural Analgesia on Uterine Electromyographic Activities during Labor.

Epidural analgesia is effective in relieving pain during labor. However, concerns as to compromised labor progress and outcomes arise. This study aimed to assess the effect of patient-controlled epidural analgesia (PCEA) with ropivacaine on uterine electromyography (EMG) activities and outcomes in labor. A total of 213 pregnant women were divided into three groups: the PCEA with ropivacaine group (n = 78), the PCEA with levobupivacaine group (n = 66), and a control group that did not receive PCEA (n = 69). Uterine EMG activities were recorded during the first stage of labor. Maternal and fetal outcomes also were assessed. The primary outcomes of this study were EMG activities. No significant differences were observed in patient demographics or neonatal weight among the three groups. Compared to the PCEA with levobupivacaine group, the control and PCEA with ropivacaine groups had lower rates of oxytocin administration (P < 0.05) and shorter durations of the first stage of labor (P < 0.05). For the EMG activities, the PCEA with ropivacaine group showed a higher power (P < 0.01) and higher peak frequency (P < 0.05) than the PCEA with levobupivacaine group. With ropivacaine, the EMG activities remained stable 30-120 min. Compared with levobupivacaine, the use of ropivacaine in PCEA has no suppressive effect on uterine EMG activities during the first stage of labor. In addition, ropivacaine leads to labor progress and delivery outcomes similar to those in the control group, as well as similar and favorable analgesic satisfaction with the use of levobupivacaine.