Erythritol aggravates gut inflammation and anxiety-like behavioral disorders induced by acute dextran sulfate sodium administration in mice.

Erythritol is a widely used sugar substitute in food and beverages with beneficial and detrimental roles in obesity and cardiovascular diseases, respectively; however, its influence on inflammatory bowel disease (IBD) and related behavioral disorders is not well understood. Here, we found that erythritol exacerbated gut inflammation by promoting macrophage infiltration and inducing M1 macrophage polarization, thus increasing gut leakage during colitis triggered by acute dextran sulfate sodium (DSS) treatment. Increased gut permeability can cause neuroinflammation and anxiety-like behavioral disorders. In conclusion, our results revealed a negative role for erythritol in gut inflammation and anxiety-like behavioral disorders induced by erythritol administration in a mouse model of acute colitis, suggesting that erythritol intake control may be necessary for IBD treatment.

Comparing the Effectiveness and Safety of MedAn with the Nishikawa Blade and UE Videolaryngoscopes for Left-Sided Double-Lumen Endobronchial Tube Intubation: A Randomized Controlled Trial.

BACKGROUND The purpose of this study was to compare the effectiveness and safety of the MedAn videolaryngoscope with the Nishikawa blade (MedAn) vs the UE videolaryngoscope (UE) for intubation with a left-sided double-lumen endobronchial tube (LDLT) in patients with normal airways. MATERIAL AND METHODS We randomly categorized 106 patients scheduled to undergo elective thoracic surgery with LDLT for one-lung ventilation into 2 groups: the UE group (Group UE) and the MedAn group (Group MedAn), using the MedAn or UE for LDLT intubation. The primary outcome was time to successful intubation. The Cormack-Lehane classification of laryngeal view was the key secondary outcome. Other secondary outcomes included first-attempt and overall intubation success rates, laryngoscopy time, LDLT placement time, operators' subjective evaluation of videolaryngoscopes, hemodynamic changes during videolaryngoscopic intubation, and adverse outcomes. RESULTS The time to successful intubation and LDLT placement time of Group MedAn were 42.0 (32.35, 47.0) s and 23.0 (18.0, 26.0) s, and it was shorter than in Group UE (median, 42 s vs 49 s, 23 s vs 30 s, P<0.001). Group MedAn had a better laryngeal view (P=0.03) and less subglottic/tracheal mucosal injury (P<0.001) than Group UE. Moreover, the operators' subjective grading of ease of laryngoscopy, quality of view, and ease of LDLT placement were higher in Group MedAn than in Group UE (P<0.05). CONCLUSIONS Compared with the UE, the MedAn could reduce the intubation time and provide a better laryngeal view and sufficient intubation space for safer LDLT intubation in patients with normal airways.

The effect of varying inhaled oxygen concentrations of high-flow nasal cannula oxygen therapy during gastroscopy with propofol sedation in elderly patients: a randomized controlled study.

BACKGROUND: Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients. METHODS: In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia. RESULTS: The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC. CONCLUSION: HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%. TRIAL REGISTRATION: This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.

WDR34 mutation from anencephaly patients impaired both SHH and PCP signaling pathways.

Neural tube defects (NTDs) are debilitating human congenital abnormalities due to failure of neural tube closure. Sonic Hedgehog (SHH) signaling is required for dorsal-ventral patterning of the neural tube. The loss of activation in SHH signaling normally causes holoprosencephaly while the loss of inhibition causes exencephaly due to failure in neural tube closure. WDR34 is a dynein intermedia chain component which is required for SHH activation. However, Wdr34 knockout mouse exhibit exencephaly. Here we screened mutations in WDR34 gene in 100 anencephaly patients of Chinese Han population. Compared to 1000 Genome Project data, two potentially disease causing missense mutations of WDR34 gene (c.1177G>A; p.G393S and c.1310A>G; p.Y437C) were identified in anencephaly patients. These two mutations did not affect the protein expression level of WDR34. Luciferase reporter and endogenous target gene expression level showed that both mutations are lose-of-function mutations in SHH signaling. Surprisingly, WDR34 could promote planar cell polarity (PCP) signaling and the G393S lost this promoting effect on PCP signaling. Morpholino knockdown of wdr34 in zebrafish caused severe convergent extension defects and pericardial abnormalities. The G393S mutant has less rescuing effects than both WT and Y437C WDR34 in zebrafish. Our results suggested that mutation in WDR34 could contribute to human NTDs by affecting both SHH and PCP signaling.

Deficiency of Wdr60 and Wdr34 cause distinct neural tube malformation phenotypes in early embryos.

Cilia are specialized organelles that extend from plasma membrane, functioning as antennas for signal transduction and are involved in embryonic morphogenesis. Dysfunction of cilia lead to many developmental defects, including neural tube defects (NTDs). Heterodimer WDR60-WDR34 (WD repeat domain 60 and 34) are intermediate chains of motor protein dynein-2, which play important roles in ciliary retrograde transport. It has been reported that disruption of Wdr34 in mouse model results in NTDs and defects of Sonic Hedgehog (SHH) signaling. However, no Wdr60 deficiency mouse model has been reported yet. In this study, piggyBac (PB) transposon is used to interfere Wdr60 and Wdr34 expression respectively to establish Wdr60 PB/PB and Wdr34 PB/PB mouse models. We found that the expression of Wdr60 or Wdr34 is significantly decreased in the homozygote mice. Wdr60 homozygote mice die around E13.5 to E14.5, while Wdr34 homozygote mice die around E10.5 to E11.5. WDR60 is highly expressed in the head region at E10.5 and Wdr60 PB/PB embryos have head malformation. RNAseq and qRT-PCR experiments revealed that Sonic Hedgehog signaling is also downregulated in Wdr60 PB/PB head tissue, demonstrating that WDR60 is also required for promoting SHH signaling. Further experiments on mouse embryos also revealed that the expression levels of planar cell polarity (PCP) components such as CELSR1 and downstream signal molecule c-Jun were downregulated in WDR34 homozygotes compared to wildtype littermates. Coincidently, we observed much higher ratio of open cranial and caudal neural tube in Wdr34 PB/PB mice. CO-IP experiment showed that WDR60 and WDR34 both interact with IFT88, but only WDR34 interacts with IFT140. Taken together, WDR60 and WDR34 play overlapped and distinct functions in modulating neural tube development.

The Median Effective Volume of 0.375% Ropivacaine for Ultrasound-guided Anterior Suprascapular Nerve Block in Arthroscopic Shoulder Surgery.

BACKGROUND: The suprascapular nerve (SSN) is an important nerve that contributes to shoulder joint sensation and movement. The anterior suprascapular nerve block (aSSNB) has the potential for noninferior analgesic effect compared with the interscalene block while preserving respiratory function. This study investigated the median effective volume (MEV) of 0.375% ropivacaine in aSSNB for analgesic effect among patients undergoing arthroscopic shoulder surgery. OBJECTIVES: Our primary objective was the MEV. The secondary objectives included the 24 hour sufentanil consumption, 24 hour patient-controlled analgesia (PCA) presses, and incidences of diaphragm impairment. STUDY DESIGN: Prospective registered (ChiCTR2300070129), single-armed, volume-finding study. SETTING: This study was conducted in a tertiary, single center. METHODS: There were 23 patients who completed the study. Using an up-and-down process, patients enrolled in the study received different volumes of 0.375% ropivacaine for an aSSNB adjusted based on the success or failure of the previous patient in the study's block by increasing or decreasing the volume by 3 mL. The first patient received 15 mL of 0.375% ropivacaine. The nerve blocks were evaluated by the sensory score of the C5 and C6 dermatomes. RESULTS: MEV50 (50% of the patients) was 6 mL (95% CI, 5.78 - 6.78 mL), and MEV95 (95% of the patients) was 13.88 mL (95% CI, 13.37 - 14.87 mL). There was no significant difference in the PCA presses, 24 hour sufentanil consumption, and incidences of diaphragm impairments between successful and unsuccessful blocks. LIMITATIONS: Our study focused on the analgesic effect rather than hemi-diaphragmatic paralysis with 0.375% ropivacaine for an aSSNB. The study also did not test varying ropivacaine concentrations while keeping the volume constant. Further investigation with varying concentrations and a larger sample size is indicated to address the optimal volume and concentration to balance analgesia and diaphragm function. CONCLUSIONS: To produce effective analgesic effect, the MEV50 is 6 mL, and the MEV95 is 13.88 mL in patients undergoing arthroscopic shoulder surgery who receive an aSSNB using 0.375% ropivacaine for analgesia.