Effectiveness and safety of remimazolam combined with alfentanil in hysteroscopic examination: A prospective, randomized, single-blind trial.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50). METHODS: Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon's up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination. MAIN RESULTS: The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195-0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261-1.619). CONCLUSION: In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.

Upregulation of eIF2α by m6A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m6A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m6A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.

Extensive jejunal injury is repaired by migration and transdifferentiation of ileal enterocytes in zebrafish.

A major cause of intestinal failure (IF) is intestinal epithelium necrosis and massive loss of enterocytes, especially in the jejunum, the major intestinal segment in charge of nutrient absorption. However, mechanisms underlying jejunal epithelial regeneration after extensive loss of enterocytes remain elusive. Here, we apply a genetic ablation system to induce extensive damage to jejunal enterocytes in zebrafish, mimicking the jejunal epithelium necrosis that causes IF. In response to injury, proliferation and filopodia/lamellipodia drive anterior migration of the ileal enterocytes into the injured jejunum. The migrated fabp6+ ileal enterocytes transdifferentiate into fabp2+ jejunal enterocytes to fulfill the regeneration, consisting of dedifferentiation to precursor status followed by redifferentiation. The dedifferentiation is activated by the IL1ß-NFκB axis, whose agonist promotes regeneration. Extensive jejunal epithelial damage is repaired by the migration and transdifferentiation of ileal enterocytes, revealing an intersegmental migration mechanism of intestinal regeneration and providing potential therapeutic targets for IF caused by jejunal epithelium necrosis.

A Statistical Investigation of Factors Influencing the Magnetotail Twist at Mars.

The Martian magnetotail exhibits a highly twisted configuration, shifting in response to changes in polarity of the interplanetary magnetic field's (IMF) dawn-dusk (B Y) component. Here, we analyze ∼6000 MAVEN orbits to quantify the degree of magnetotail twisting (θ Twist) and assess variations as a function of (a) strong planetary crustal field location, (b) Mars season, and (c) downtail distance. The results demonstrate that θ Twist is larger for a duskward (+B Y) IMF orientation a majority of the time. This preference is likely due to the local orientation of crustal magnetic fields across the surface of Mars, where a +B Y IMF orientation presents ideal conditions for magnetic reconnection to occur. Additionally, we observe an increase in θ Twist with downtail distance, similar to Earth's magnetotail. These findings suggest that coupling between the IMF and moderate-to-weak crustal field regions may play a major role in determining the magnetospheric structure at Mars.

Change of lipids in whelks (Neptunea arthritica cumingi Crosse and Neverita didyma) during cold storage.

The objective of this study was to evaluate the change of lipids in two whelk samples during cold storage. Results showed that the peroxide value (PV) and thiobarbituric acid reactive substance (TBARS) increased while the percentage of polyunsaturated fatty acid decreased, indicating that lipid oxidation occurred. The cold storage significantly reduced the levels of triacylglycerol (TAG), polar lipid (PoL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) but increased the levels of acid value (AV), free fatty acid (FFA) and monoacylglycerol, suggesting the hydrolysis of lipids. Moreover, the results showed that the lipoxygenase, acid lipase and phospholipase contributed to the hydrolysis and oxidation of lipids in the two whelks. Additionally, partial least squares discriminant analysis showed PC was positively correlated with PE, PoL and TAG, but negatively correlated with AV, FFA, PV and TBARS, indicating there is a close relationship between hydrolysis and oxidation of lipids.

Effects of hot air drying process on lipid quality of whelks Neptunea arthritica cumingi Crosse and Neverita didyma.

Whelks Neptunea arthritica cumingi Crosse and Neverita didyma were processed by hot air drying and changes of thei lipids and the mechanism involved were evaluated by analyzing peroxide value, thiobarbituric acid-reactive substances, total oxidation value, fatty acid composition, activities of lipases and lipoxygenase (LOX), as well as contents of triacylglycerol (TAG), free fatty acid (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The processing significantly decreased the contents of PC, PE and TAG but increased the content of FFA. The presence of acid lipase and phospholipase in whelk tissues and their activity preservation during processing suggest that the enzymes may help hydrolyze lipids. By contrast, the reduction of PC, PE and TAG was more pronounced than the increase in FFA in whelk tissues upon processing, indicating the oxidative degradation of FFA. LOX may play a role in lipid oxidation due to the stability of the starting components during processing.

The CCCH-type zinc finger transcription factor Zc3h8 represses NF-κB-mediated inflammation in digestive organs in zebrafish.

Degenerative diseases of organs lead to their impaired function. The cellular and molecular mechanisms underlying organ degeneration are therefore of great research and clinical interest but are currently incompletely characterized. Here, using a forward-genetic screen for genes regulating liver development and function in zebrafish, we identified a cq5 mutant that exhibited a liver-degeneration phenotype at 5 days postfertilization, the developmental stage at which a functional liver develops. Positional cloning revealed that the liver degeneration was caused by a single point mutation in the gene zc3h8 (zinc finger CCCH-type containing 8), changing a highly conserved histidine to glutamine at position 353 of the Zc3h8 protein. The zc3h8 mutation-induced liver degeneration in the mutant was accompanied by reduced proliferation, increased apoptosis, and macrophage phagocytosis of hepatocytes. Transcriptional profile analyses revealed up-regulation and activation of both proinflammatory cytokines and the NF-κB signaling pathway in the zc3h8 mutant. Suppression of NF-κB signaling activity efficiently rescued the proinflammatory cytokine response, as well as the inflammation-mediated liver degeneration phenotype of the mutant. Of note, the zc3h8 mutation-induced degeneration of several other organs, including the gut and exocrine pancreas, indicating that Zc3h8 is a general repressor of inflammation in zebrafish. Collectively, our findings demonstrate that Zc3h8 maintains organ homeostasis by inhibiting the NF-κB-mediated inflammatory response in zebrafish and that Zc3h8 dysfunction causes degeneration of multiple organs, including the liver, gut, and pancreas.

Direct infusion mass spectrometric identification of molecular species of glycerophospholipid in three species of edible whelk from Yellow Sea.

Whelk has been exploited commercially as a delicacy for a long time. Although previous studies have suggested that whelk might serve as a potential rich source of long chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) enriched phospholipid (PL), the molecular species profile of the PL have not been reported yet. In this study, more than 220 molecular species of glycerophospholipid (GP) belonging to eight classes including glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoserine, glycerophosphoinositol, lysoglycerophosphocholine, lysoglycerophosphoethanolamine, lysoglycerophosphoserine and lysoglycerophosphoinositol in three species of edible whelks (Buccinium yokomaruae, Neptunea arthritica cumingi Cosse and Volutharpa ampullaceal) were identified for the first time by using direct infusion tandem mass spectrometric method. Most of the predominant GP molecular species contained n-3 LC-PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Meanwhile, the whelk lipids contained a high proportion of PL (32.92-55.55% of total lipids) and PUFA (30.45-41.42% of total FA). Among PL, phosphatidylcholine (44.18-65.49mol%) was dominant.