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.

Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma.

Background: Cuproptosis is a novel type of regulated cell death and is reported to promote tumor occurrence and progression. However, whether a cuproptosis-related signature has an impact on hepatocellular carcinoma (HCC) is still unclear. Materials and methods: We analyzed the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and searched for tumor types with different cuproptosis patterns through consistent clustering of cuproptosis genes. We then constructed a Cuproptosis-Related Genes (CRGs)-based risk signature through LASSO COX regression, and further analyzed its impact on the prognosis, clinical characteristics, immune cell infiltration, and drug sensitivity of HCC. Results: We identified the expression changes of 10 cuproptosis-related genes in HCC, and all the patients can be divided into two subtypes with different prognosis by applying the consensus clustering algorithm. We then constructed a cuproptosis-related risk signature and identified five CRGs, which were highly correlated with prognosis and representative of this gene set, namely G6PD, PRR11, KIF20A, EZH2, and CDCA8. Patients in the low CRGs signature group had a favorable prognosis. We further validated the CRGs signature in ICGC cohorts and got consistent results. Besides, we also discovered that the CRGs signature was significantly associated with a variety of clinical characteristics, different immune landscapes and drug sensitivity. Moreover, we explored that the high CRGs signature group was more sensitive to immunotherapy. Conclusion: Our integrative analysis demonstrated the potential molecular signature and clinical applications of CRGs in HCC. The model based on CRGs can precisely predict the survival outcomes of HCC, and help better guide risk stratification and treatment strategy for HCC patients.

The effect of OSA on the negative pressure and acoustic compliance of middle ear cavity in children.

OBJECTIVE: To explore the effect of obstructive sleep apnea (OSA) on the negative pressure and acoustic compliance of middle ear cavity in children. METHODS: The clinical data of 258 children with suspected OSA, who complained of mouth breathing or snoring at night in the Department of Otolaryngology Head and neck surgery of the Second Affiliated Hospital of Xi'an Jiao Tong University from August 2020 to March 2022, were enrolled and analyzed retrospectively. The OSA and otitis media with effusion (OME) were determined by polysomnography (PSG) and acoustic immittance examination, respectively. Then, the parameters of tympanometry were compared between OSA and non-OSA children or among the children with various severity of OSA. RESULTS: There was no significant difference in the incidence of OME between children with OSA and those with non-OSA (15.80% vs 11.80%, P = 0.422). Compared with non-OSA children, OSA children had lower negative pressure (-56.42 vs -12.38, P < 0.001) and higher acoustic compliance (0.45 vs 0.38, P = 0.030) in middle ear cavity. There were also significant differences in negative pressure and acoustic compliance among children with mild, moderate and severe OSA (P < 0.001; P = 0.001). However, only the absolute value of negative pressure was markedly decreased after surgical therapy accompanied with transformation from OSA to non-OSA (-156.67 vs -45.67, P < 0.05), while this was not observed for acoustic compliance (0.48 vs 0.40, P > 0.05). CONCLUSION: OSA may have an adverse influence on the negative pressure and acoustic compliance of middle ear cavity in children.

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.

[The application of NBI endoscopy in finding concealed primary lesions of misdiagnosis of oropharyngeal cancer].

Objective:The aim of this study is to analyze the application value of NBI endoscopy in finding the concealed primary lesions of misdiagnosis of oropharyngeal cancer. Methods:The clinical data of patients with missed oropharyngeal cancer treated in the Department of Otolaryngology Head and neck surgery, the Second Affiliated Hospital of Xi'an Jiaotong University from May 2018 to June 2021, were retrospectively studied, and the missed diagnosis was also analyzed combined with results of NBI endoscopy. Results:In 31 cases of misdiagnosis of oropharyngeal cancer patients, including 25 males and 6 females, there was no significant difference in age, BMI index, course of disease and TNM stage （P> 0.05）, and the pharyngeal or cervical symptoms were the first clinical manifestations of them, containing pharyngeal pain in 17 cases（54.8%） , pharyngeal foreign body sensation in 4 cases（12.9%） and unilateral cervical mass in 10 cases （32.3%）. No laryngoscopy was performed （21 cases） or no primary lesion was found by laryngoscopy （10 cases） at initial diagnosis. Among them, "inflammatory lesions" were given anti-inflammatory treatment with ineffective results or surgical resection was explored for suspicious lesions （17 cases）, or imaging examination （9 cases, including 6 cases with CT and MRI, 3 cases with PET-CT） and cervical lymph node biopsy （5 cases） were carried out for further diagnosis. According to these results, they were given ordinary laryngoscope （2 cases） or NBI endoscopy （29 cases） subsequently, finally they were confirmed as oropharyngeal squamous cellcarcinoma after localized biopsy at the suspicious lesions, indicating that the accuracy of NBI endoscopy in finding the concealed primary lesions of oropharyngeal cancer （93.55%） is significantly higher than that of ordinary electronic laryngoscope （6.45%）（χ²=43.613, P<0.01）. Conclusion:NBI endoscopy has unique advantages in finding oropharyngeal cancer in concealed parts such as tonsil, root of tongue, soft palate and lateral wall of oropharynx, which could reduce misdiagnosis of oropharyngeal cancer.

[Clinical features of diffuse large B-cell lymphoma in head and neck].

Objective:To investigate the clinical features of diffuse large B-cell lymphoma （DLBCL） of head and neck. Methods:A retrospective study was conducted among patients with DLBCL in the Department of otolaryngology and head and neck surgery of the Second Affiliated Hospital of Xi'an Jiaotong University from July 2011 to September 2021. The disease location, clinical manifestations, diagnosis, treatment and prognosis of DLBCL patients in head and neck were analyzed retrospectively. Results:Oropharynx（27 cases, including 25 cases in tonsil）, neck（29 cases）, nasopharynx and nasal cavity （7 cases）were included in 63 cases of DLBCL in head and neck. Pharyngalgia, pharyngeal foreign body sensation and dysphagia were the most common manifestations of oropharyngeal DLBCL, while nasal obstruction, runny nose and hyposmia were the initial manifestations of nasal and nasopharyngeal DLBCL.Under the NBI endoscopy, locally uplifted neoplasm with rough surface mucosa was observed in 34 cases DLBCL patients of oropharynx, nasopharynx and nasal cavity. Among them, 16 cases were covered with yellow-white and patchy pseudomembrane on the surface of the neoplasm, and 5 cases were detected with abnormal new vessels, including 3 cases of tonsils, 1 case of root of tongue, and 1 case of nasopharynx. Painless progressive lymphadenectasis was the common manifestation of DLBCL in head and neck, and the maximum diameter（[21.3±6.7]mm） of neck lymph nodes in the same side of DLBCL was significantly larger than that in the opposite side（[16.0±7.2]mm, P=0.009）. Sixty-three cases of DLBCL in head and neck, including 27 cases of germinal center type（GCB）, 33 cases of nongerminal center type（non-GCB）, and 3 cases of non-specific DLBCL, were confirmed the diagnosis by needle biopsy（33 cases, 52.4%） and surgical resection（30 cases, 47.6%）. The imaging features of DLBCL in head and neck were mostly showed as local soft tissue masses with uniform density and uneven enhancement, and the surrounding structures were often compressed and displaced. All the patients were treated with standard R-CHOP chemotherapy regimens, and overall survival was longer in normal LDH, and overall survival of the patients at low risk of IPI was longer than those at medium-high or high risk of IPI（PLDH=0.011, PIPI=0.022, P<0.05）. Conclusion:DLBCL mainly occurs in oropharynx, especially the unilateral tonsil. When flake yellow-white pseudomembrane adhesion and abnormal neovessels on the surface of the mass are detected under endoscopy, and the ultrasound suggested multiple enlarged lymph nodes in the neck with large iplateral lymph nodes, the possibility of DLBCL should be considered. Surgical resection could be performed for diagnosis if necessary, and early diagnosis would have a better prognosis.

[Effect of proton pump inhibitort on salivary pepsin concentration in patients with laryngopharyngeal reflux].

Objective:To investigate the effect of proton pump inhibitor（PPI） treatment on salivary pepsin concentration in laryngopharyngeal reflux（LPR）. Methods:152 patients with suspected LPR complaining non-specific symptoms such as foreign body sensation, dry throat, phlegm and other non-specific symptoms were enrolled， in the Second Affiliated Hospital of Xi'an Jiaotong University from August 2019 to December 2020. According to the scores of reflux symptom index（RSI） and reflux finding score（RFS）, all the patients were divided into LPR （+） group and LPR （-） group, RSI （+） group and RSI （-） group, RFS （+） group and RFS （-） group . Patients in the LPR （+） group were reassessed after 1 month of PPI treatment. Saliva samples were collected from all the patients at initial diagnosis and follow-up diagnosis after treatment. The salivary pepsin concentration was determined by enzyme linked immunosorbent assay （ELISA）. The differences of RSI, RFS scores and salivary pepsin concentrations before and after treatment were compared. Results:The median concentration of salivary pepsin in LPR （+） group was significantly higher than that in LPR （-） group, and （73.01 ng/mL vs 25.66 ng/mL, P<0.01）, the median concentration of salivary pepsin in RFS （+） group were significantly higher than that in RFS （-） group（78.00 ng/mL vs 35.79 ng/mL, P<0.01） Furthermore, the median scores of RSI （11.00 vs 7.00, P<0.05） and RFS （9.00 vs 7.00, P<0.01） of LPR （+） patients notably decreased after PPI treatment for 1 month, and the salivary pepsin median concentration was memorably lower than that before treatment（53.60 ng/mL vs 46.49 ng/mL, P<0.05）. Meanwhile, the scores of symptoms such as pharyngeal paraesthesia, heartburn, chest pain, stomachache, and the scores of signs such as false vocal fold, erythema or congestion, vocal fold edema, posterior commissure hypertrophy and thick endolaryngeal mucus were conspicuously lower after treatment than those before treatment（P<0.05）. Conclusion:After 1 month of PPI treatment, the scores of partial symptoms and signs, and the salivary pepsin concentrations of LPR patients decreased significantly, suggesting that pepsin plays an important role in the pathogenesis of LPR, and pepsin may be closely related to the symptoms and signs such as pharyngeal paraesthesia and vocal fold edema.

Aberrant methylation­mediated decrease of lncRNA HNF1A­AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT.

Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression levels of genes, including long non­coding RNAs (lncRNAs), in tumors. However, to the best of our knowledge, the expression and function of hepatic nuclear factor 1α antisense RNA 1 (HNF1A­AS1) and its methylation condition have not yet been reported in the development and progression of laryngeal squamous cell carcinoma (LSCC). In the present study, the expression and methylation of HNF1A­AS1 were first examined by reverse transcription­quantitative PCR, bisulfite genomic sequencing and methylation­specific polymerase chain reaction in samples from patients with LSCC, which were based on the in silico analysis using The Cancer Genome Atlas data, and were then further verified in LSCC cell lines with and without 5­Aza­2'­deoxycytidine (5­Aza­dC) treatment. Subsequently, proliferation, cell cycle distribution, migration and invasion of LSCC cells following either knockdown or overexpression of HNF1A­AS1 were determined in vitro. Furthermore, the characteristic of HNF1A­AS1 on epithelial­mesenchymal transition (EMT) changes was investigated in vitro and in vivo. The associations between the expression levels of HNF1A­AS1 and tumorigenicity and cervical lymph node metastasis were assessed in a xenograft model in nude mice. In the present study, downregulation and hypermethylation in CpG sites of HNF1A­AS1 were detected in LSCC tissues as well as metastatic cervical lymph nodes samples when compared with those in the adjacent non­tumor tissues. Additionally, HNF1A­AS1 inhibited proliferation, migration and invasion of LSCC cells in vitro by regulating the process of EMT. Furthermore, HNF1A­AS1 inhibited tumor growth and metastasis by regulating EMT in vivo. Additionally, the migration and invasion abilities, and the expression levels of HNF1A­AS1 and EMT markers in LSCC cells were significantly reversed by treatment with 5­Aza­dC. In summary, HNF1A­AS1 was downregulated by hypermethylation in LSCC and laryngeal cancer cells. These findings suggested that HNF1A­AS1 could serve as a tumor suppressor lncRNA in LSCC by regulating the EMT process, leading to the discovery of novel therapeutic targets and strategies for the treatment of patients with LSCC.

EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3.

Enhancer of Zeste Homolog 2(EZH2), which can change chromatin structure by tri-methylation of the 27th lysine of H3 in nucleosome histone (H3K27me3), is involved in different types of cancers. However, the role and mechanism underlying aberrant EZH2 expression in laryngeal squamous cells carcinoma (LSCC) remain unclear. In the present study, we found that down-regulation of EZH2 and H3K27me3 in LSCC cells (Hep-2 and SCC10A) resulted in an mesenchymal-epithelial transition(MET) like cell morphology and lower invasion in vitro, weakened tumor growth, intrahepatic and pulmonary metastasis in vivo. Furthermore, EZH2 promoted the epithelial-mesenchymal transition(EMT) process through down-regulation of Ca2+ dependent cell adhesion molecule E (E-cadherin) and up-regulation of H3K27me3 in vitro and in vivo. Moreover, E-cadherin was transcriptionally induced upon stable knockdown of EZH2, and quantitative chromatin immunoprecipitation(qChIP) analysis confirmed the depletion of H3K27me3 enrichment on E-cadherin promoter upon EZH2 knockdown in Hep-2 and SCC10A cells. In addition, the expression of EZH2 was positively correlated with that of H3K27me3 and both of them were inversely correlated with E-cadherin expression in human LSCC tissues. In summary, this study indicated that EZH2 promoted invasion and metastasis of LSCC via EMT through H3K27me3.

Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

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.

[The expression and clinical significance of pepsin and pepsinogen in patients with otitis media with effusion].

OBJECTIVE: To analyze the role and significance of pepsin and pepsinogen in the pathogenesis of OME in children. METHOD: Pediatric patients with otitis media aged 2-8 years who enrolled in our department of the hospital from May of 2012 to December of 2012 were set as experimental group (38 cases, 48 ears) which should be underwent tympanic membrane puncture/tube insertion. Meanwhile, pediatric patients waiting for cochlear implant without otitis media (10 ears), were set as control group. Middle ear lavage fluid and plasma samples from the two groups were collected and detected using enzyme-linked immune method for pepsin and pepsinogen. RESULT: The concentrations of pepsin and pepsinogen in the middle ear lavage fluid of OME group [(48.8 ± 415.99) ng/ml and 676.32 ± 336.71)ng/ml] were significantly higher than those in the control group [(8.20 ± 4.59)ng/ml and (77.27 ± 50.33) ng/ml] (P < 0.01). Meanwhile, the concentration of pepsinogen in the middle ear lavage of OME patients was significantly higher than that of plasma (P < 0.01). The concentration of pepsin in the middle ear lavage fluid from the dry ear subgroup was lower than those in the serum ear and mucous ear subgroups (P < 0.01), but there was no significant difference about concentrations of pepsinogen among the dry ear, serum ear and mucous ear subgroups (P > 0.05). CONCLUSION: Pepsin and pepsinogen in the middle ear cavity of OME patients maybe originated from laryngopharyngeal reflux (LPR), indicating that LPR is associated with the pathogenesis of OME in children.

[The therapeutic effect of proton pump inhibitor on alleviation of hoarseness symptoms in patients with laryngopharyngeal reflux].

OBJECTIVE: To analyze the therapeutic effect of proton pump inhibitor(PPI) on alleviation of hoarseness symptoms in patients with laryngopharyngeal reflux(LPR). METHOD: The LPR outpatients in ENT department of our hospital(60 cases)complained of hoarseness were enrolled in the study from August of 2013 to October of 2014. All of them were randomly divided into group A and B. The individuals in group A (30 cases) taked golden voice capsule to treat for 3 months, while the individuals in group B (30 cases) taked golden voice capsule and omeprazole to treat for 3 months. The data about reflux symptom index (RSI), reflux finding score (RFS) and voice handicap index (VHI)from the first month to the third month after treatment were recorded and compared group A with group B. RESULT: The scores of RSI and RFS in patients (60 cases) before treatment were significantly correlated with their VHI (r=0. 823, P<0. 01; r=0. 873, P<0. 01). The score changes of RSI and VHI from the first to the third month after treatment in group B were significantly higher than those in group A (P<0. 01). Meanwhile, the score changes of RFS from the third month after treatment in group B were significantly higher than those in group A (t=8. 307, P<. 01), but the differences were not significant for RFS from the first to the second month after treatment between group A and group B(t=1. 128, P>0. 05; t=0. 376, P> 0. 05). CONCLUSION: PPI therapy could significantly alleviate the hoarseness symptom in LPR patients.

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis.

Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-κB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NF-κB activation and restored the expression of PXR target genes in tumor necrosis factor-α-stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-κB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-κB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-κB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium-induced experimental colitis, which was associated with restored PXR/NF-κB signaling. This study indicates that ginsenosides may elicit anti-inflammatory effects via targeting PXR/NF-κB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-κB interaction in therapy for inflammatory bowel disease.

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.