Microbiome Metabolomic Analysis of the Anxiolytic Effect of Baihe Dihuang Decoction in a Rat Model of Chronic Restraint Stress.

Purpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics. Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters. Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment. Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.

Submucosal Clustered Brownish Microvessels Based on NBI Endoscopy: A Characteristic of LPR.

OBJECTIVE: This study aimed to analyze the characteristics of laryngopharyngeal reflux (LPR) by using narrow band imaging (NBI) endoscopy. STUDY DESIGN: A prospective study. SETTING: A large-volume practice with tertiary care providers. METHODS: A total of 67 patients with suspected LPR who underwent 24-hour multichannel intraluminal impedance-pH monitoring were included from June 2020 to March 2022. Manifestations of NBI endoscopy included submucosal clustered brownish microvessels (CBMs), spotted brownish microvessels, and no special microvessels; the latter 2 formed the non-CBM group. The manifestations of all patients and their changes were observed after 8 weeks of proton pump inhibitor and symptomatic treatment for patients with LPR, and symptomatic treatment for patients without LPR. RESULTS: According to the results of 24-hour multichannel intraluminal impedance-pH monitoring, the incidence of submucosal CBMs was significantly higher in patients with LPR (30 cases) than in those without LPR (37 cases, P < .001), particularly in the posterior cricoid area (P < .001). Besides Reflux Finding Score, the incidence of signs such as subglottic edema and vocal fold edema was significantly higher in the CBM group than the non-CBM group (P < .05). Finally, 22 patients with LPR (91.7%) and only 2 patients without LPR (28.6%) underwent a transformation from CBMs to spotted brownish microvessels after continuous medication for 8 weeks in the CBM group (χ2 = 15.916, P < .001), while no significant change was observed in patients with or without LPR in the non-CBM group (P > .05). CONCLUSION: Submucosal CBMs in the posterior cricoid area under NBI endoscopy may be a characteristic of LPR.

The effects of Helicobacter pylori eradication therapy on salivary pepsin concentration in patients with laryngopharyngeal reflux.

OBJECTIVE: To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. MATERIALS AND METHODS: A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. RESULTS: The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (-) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (-) subgroup either in LPR patients (75.24 ng/ml vs. 61.39 ng/ml, P = 0.005) or the non-LPR patients (78.42 ng/ml vs. 48.96 ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs. 74.15 ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). CONCLUSION: HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration.

Effects of different bronchoalveolar lavage methods on tracheobronchial foreign body patients.

OBJECTIVES/HYPOTHESIS: To compare the different effects of bronchoalveolar lavage (BAL) with diverse combinations of lidocaine, epinephrine, and dexamethasone on pediatric patients with an inhaled tracheobronchial foreign body (TFB). STUDY DESIGN: Randomized controlled study. METHODS: Two hundred forty cases of pediatric patients with inhaled TFB were included in this study, and were randomly divided into four groups using three kinds of drugs for BAL, namely 0.9% saline (S) group, 2% lidocaine with diluted epinephrine (LE) group, 2% lidocaine with diluted epinephrine and 0.5% dexamethasone (LED), control group (C) without BAL. The incidences of intraoperative or postoperative complications and recovery periods were compared. Meanwhile, the concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in BAL fluids and plasma were evaluated by enzyme-linked immunosorbent assay. RESULTS: The incidences of bronchospasm, hypoxemia, and postoperative fever were significantly lower in the LED group than other groups (P < .001). Fever after the TFB removal procedure appeared later in the LED group than the other groups. The improvement and healing periods in the LE and LED groups were significantly shorter than those in the C and S groups (P < .001). The concentrations of IL-1ß, IL-6, and TNF-α in BAL fluids were significantly higher in the LE and LED groups than those in the S group (P < .001), but those in the plasma of the C and S groups were lower compared with the LE and LED groups (P < .001). CONCLUSIONS: BAL with lidocaine, epinephrine, and dexamethasone could promote recovery for TFB patients and reduce incidences of complications, possibly by regulating release of proinflammatory cytokines. LEVEL OF EVIDENCE: 1b.

Pepsin deteriorates prognosis of children with otitis media with effusion who undergo myringotomy or tympanostomy tube insertion.

OBJECTIVE: To investigate the concentrations of pepsin and pepsinogen within the middle ear cavity and determine whether pepsin and pepsinogen affect the prognosis of children with otitis media with effusion (OME). METHODS: All middle-ear lavage fluid from patients with OME undergoing myringotomy (M subgroup) or tympanostomy tube insertion (T subgroup) was collected and pepsin and pepsinogen were detected using enzyme-linked immunosorbent assay. After close follow-up over 2 years, the effects of pepsin and pepsinogen on the prognosis of the patients with OME in the M and T subgroups were analyzed. RESULTS: The average pepsin and pepsinogen concentrations were significantly lower in the M subgroup (n=54; 24.38±16.10mg/mL and 286.49±91.95mg/mL, respectively) than in the T subgroup (n=55; 45.56±16.60mg/mL and 664.92±107.06mg/mL; t=2.484, P=0.018 and t=2.670, P=0.011, respectively). In the M subgroup, the average time to tympanic membrane healing and tympanic pressure restoration to normal was much longer in pepsin(+) patients (17.0±2.0 days and 26.0±2.5 days, respectively) than in pepsin(-) patients (14.0±1.1 days and 22.0±1.0 days; t=3.871, P=0.001 and t=5.734, P=0.000, respectively), and the hearing level of pepsin(+) patients with OME ascended to 13.08±1.19dB, which was much lower than that of pepsin(-) patients (18.29±1.27dB; t=11.001, P=0.000). In the T subgroup, the complication rate including otorrhea and myringosclerosis was much higher in patients with high pepsin concentrations than in those with low pepsin concentrations (P<0.05). Finally, in both subgroups, the recurrence rates of OME in pepsin(+) or patients with high pepsin concentrations (34.6% [9/26] and 28.6% [10/35]) were significantly higher than those in pepsin(-) or low pepsin concentrations (10.7% [3/28] and 5.0% [1/20]; χ(2)=4.456, P=0.035 and χ(2)=4.420, P=0.036). However, pepsinogen had no significant effect on OME prognosis or recurrence. CONCLUSION: Pepsin but not pepsinogen could postpone tympanic membrane healing and pressure restoration in children with OME undergoing myringotomy and increase the incidence of recurrence and complications including otorrhea and myringosclerosis for those undergoing tympanostomy tube insertion. Therefore, pepsin could be considered a poor prognostic factor for OME, further emphasizing the important role of pepsin in OME pathogenesis.