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Purpose: It is controversial for the optimal time of breast cancer surgery after COVID-19 infection. Purpose was to assess the risk of postoperative complication in breast cancer patients with COVID-19 infection, in order to select optimal surgery timing after COVID-19 infection., Methods: Breast cancer patients infected with COVID-19 and performed surgery between December 20th, 2022 to March 20th, 2023 were included in this prospective study (n = 577). Patients performed surgery between May 1, 2019 to October 1, 2019 were listed as control group (n = 329). They had not been infected with COVID-19 before surgery. Patients were grouped by time of surgery relative to COVID-19 infection. Database was evaluated using logistic regression., Results: Patients infected with COVID-19 had a higher incidence of complications after surgery compared to that not-COVID-19 infection (6.59% vs. 3.04%). Multivariable logistic analysis demonstrated that timing of surgery was associated with complications (OR = 4.253; 95% CI: 0.855-21.153, P = 0.044). Patients performed surgery within 2 weeks after COVID-19 infection had the highest rates of complication (17.65%) when compared with other groups, while the incidence was decreased into 5.51% when surgery 2 weeks or more after COVID-19 infection. With a median follow-up was 10 months, all patients with complications were recovered without serious complications or death, which had no adverse effect on subsequent anti-tumor therapy., Conclusions: It needs to be cautious when breast cancer surgery was performed within 2 weeks after COVID-19 infection. Although the incidence of complications in patients undergoing surgery 2 weeks after COVID-19 infection is still slightly high, surgery might be recommended considering urgency of treatment, good prognosis of complications and the lack of influence on subsequent adjuvant therapy., (© 2024. The Author(s).)

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal., Methods: Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice's livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized., Results: WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal., Conclusions: The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence., Competing Interests: JGF has been an associate editor of the Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflicts of interest related to this publication., (© 2024 Authors.)

Objectives: Artesunate (ART) is a water-soluble derivative of artemisinin, which has shown anti-inflammatory, anti-tumor, and immunomodulating effects. We aimed to investigate the potential therapeutic effects and mechanisms of ART in metabolic dysfunction-associated steatohepatitis (MASH)., Methods: The mice were randomly divided into the control group, high-fat, high-cholesterol diet-induced MASH group, and the MASH treated with ART (30 mg/kg once daily) group. Liver enzymes, lipids, and histological features were compared among groups. The molecular mechanisms were studied by transcriptomic and lipidomics analyses of liver tissues., Results: The mice of the MASH group had significantly increased hepatic fat deposition and inflammation in terms of biochemical indicators and pathological manifestations than the control group. The ART-treated group had improved plasma liver enzymes and hepatic cholesterol, especially at week 4 of intervention (p < 0.05). A total of 513 differentially expressed genes and 59 differentially expressed lipids were identified in the MASH group and the MASH+ART group. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment test showed that ART regulated glycerolipid metabolism pathway and enhanced fatty acid degradation. Peroxisome proliferator-activated receptor (PPAR)-α acted as a key transcription factor in the treatment of MASH with ART, which was confirmed by cell experiment., Conclusions: ART significantly improved fat deposition and inflammatory manifestations in MASH mice, with potential therapeutic effects. The mechanism of artemisinin treatment for MASH may involve extensive regulation of downstream genes by upstream transcription factors, such as PPAR-α, to restore hepatic lipid homeostasis., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life., Methods: We generated male hepatocyte-specific NAT10 knockout (Nat10 HKO ) mice and mated them with female Nat10 fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes., Results: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10 HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA., Conclusions: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD., (© 2024 The Obesity Society.)

Background: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD, 1 normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT, 2 has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis., Methods: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported., Results: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4 %) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40 %)., Limitations: Limitations include potential bias in study selection, study methods of analysis, and generalization of results., Conclusions: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The spider of Ectatosticta davidi, belonging to the lamp-shade web spider family, Hypochilidae, which is closely related to Hypochilidae and Filistatidae and recovered as sister of the rest Araneomorphs spiders. Here we show the final assembled genome of E. davidi with 2.16 Gb in 15 chromosomes. Then we confirm the evolutionary position of Hypochilidae. Moreover, we find that the GMC gene family exhibit high conservation throughout the evolution of true spiders. We also find that the MaSp genes of E. davidi may represent an early stage of MaSp and MiSp genes in other true spiders, while CrSp shares a common origin with AgSp and PySp but differ from MaSp. Altogether, this study contributes to addressing the limited availability of genomic sequences from Hypochilidae spiders, and provides a valuable resource for investigating the genomic evolution of spiders., (© 2023. The Author(s).)

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis., (© 2023. The Author(s).)

Objectives: To determine whether hyperammonemia has a direct impact on steatohepatitis in mice fed with a high-fat diet (HFD)., Methods: Male C57BL/6 mice were divided into two groups receiving either chow diet or HFD. After 12-week NASH modeling, hyperammonemia was induced by intragastric administration of ammonium chloride solution (NH 4 Cl) or liver-specific carbamoyl phosphate synthetase 1 (Cps1) knockdown. In vitro experiments were performed in HepG2 cells induced by free fatty acid (FFA) and NH 4 Cl., Results: NH 4 Cl administration led to increased levels of plasma and hepatic ammonia in NASH mice. NH 4 Cl-induced hyperammonemia did not influence liver histological changes in mice fed with HFD; however, elevated plasma cholesterol level, and an increasing trend of liver lipid content were observed. No significant effect of hyperammonemia on hepatic inflammation and fibrosis in NASH mice was found. In vitro cell experiments showed that NH 4 Cl treatment failed to increase the lipid droplet content and the expressions of de novo lipogenesis genes in HepG2 cells induced by FFA. The knockdown of Cps1 in HFD-fed mice resulted in elevated plasma ammonia levels but did not cause histological change in the liver., Conclusions: Our study revealed a limited role of ammonia in aggravating the progression of NASH. Further studies are needed to clarify the role and mechanism of ammonia in NASH development., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: High-risk alcohol use is a common surgical risk factor. Stopping or reducing alcohol use in the weeks before and after surgery could improve surgical health and outcomes. The purpose of this study was to evaluate the feasibility and acceptability of 2 interventions that address high-risk alcohol use in the context of surgery., Methods: Participants included patients scheduled for elective surgeries at an academic health system in the Midwestern United States. Recruitment took place by phone and text. Participants were included if they were 18 to 75 years old, scheduled for elective surgeries, and scored ≥5 on the Alcohol Use Disorders Identification Test-Consumption Tool. Participants were randomized to either a low-intensity intervention, brief advice (10-minute phone-based psychoeducation plus feedback session), or a higher-intensity intervention, health coaching (two 45-minute sessions including education, feedback, motivational interviewing, and goal setting). Assessments took place at baseline and at 1-month and 4-month follow-ups. Alcohol biomarkers were collected the day of surgery., Results: The final study sample included (n = 51) participants randomized to brief advice and health coaching conditions. Participants in both conditions rated interventions as satisfactory and personally relevant. Trial retention was high (86.3%) at 4 months. Attrition was significantly higher in brief advice (n = 6) relative to health coaching (n = 1). Average weekly alcohol use decreased 50% to 60% between baseline and follow-ups in both conditions. Biomarkers corroborated self-report., Conclusion: The trial demonstrated intervention feasibility and acceptability. Alcohol use changed in expected directions. The next steps include a randomized controlled trial to test intervention efficacy in reducing alcohol use and surgical complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: The concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increasingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic studies., Methods: Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were the divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2% DSS in drinking water; (3) A steatohepatitis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2% DSS in drinking water., Results: NASH plus UC had high mortality (58.3%). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was characterized by a significantly shorter colon, more colonic congestion, and a higher histopathological score ( p <0.05). Inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic ( Bcl2 , Bad , Bim , and Bax ) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups., Conclusions: Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model., Competing Interests: JGF has been an associate editor of Journal of Clinical and Translational Hepatology since 2022.The other authors have no conflicts of interest related to this publication., (© 2022 Authors.)

Cochlear distortions afford researchers and clinicians a glimpse into the conditions and properties of inner ear signal processing mechanisms. Until recently, our examination of these distortions has been limited to measuring the vibration of the basilar membrane or recording acoustic distortion output in the ear canal. Despite its importance, the generation mechanism of cochlear distortion remains a substantial task to understand. The ability to measure the vibration of the reticular lamina in rodent models is a recent experimental advance. Surprising mechanical properties have been revealed. These properties merit both discussion in context with our current understanding of distortion, and appraisal of the significance of new interpretations of cochlear mechanics. This review focusses on some of the recent data from our research groups and discusses the implications of these data on our understanding of vocalization processing in the periphery, and their influence upon future experimental directions. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized., Methods: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed., Results: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD., Conclusions: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent studies have revealed that sarcopenia is closely associated with obesity and non-alcoholic steatohepatitis (NASH). However, few attempted to explore the cause-and-effect relationship between sarcopenic obesity and NASH. In this study, we investigated muscular alterations in a rodent NASH model to elucidate their intrinsic relations and explore the potential therapeutic target. Forty-six 8-week-old and twenty 42-week-old male C57BL/6 mice (defined as young and middle-aged mice, respectively) were fed with a high-fat diet (HFD) for 12 or 20 weeks. A subset of young mice was subjected to ammonia lowering treatment by L-ornithine L-aspartate (LOLA). We examined body composition and muscle strength by nuclear magnetic resonance and grip strength meter, respectively. At the end of the 12th week, all HFD-fed mice developed typical steatohepatitis. Meanwhile, sarcopenia occurred in HFD-fed middle-aged mice, whereas young mice only demonstrated decreased grip strength. Until the end of week 20, young mice in the HFD group exhibited significant sarcopenia and obesity phenotypes, including decreased lean body mass and grip strength, and increased body fat mass and percentage body fat. Additionally, plasma ammonia level was markedly increased in HFD-fed mice of both ages at week 20. Plasma ammonia level was negatively associated with muscle strength and myofiber diameter in young mice. LOLA can significantly reduce plasma levels of ammonia, alanine aminotransaminase, aspartate aminotransaminase, and cholesterol in mice fed an HFD. Hepatic infiltration of inflammatory cells and collagen deposition area were significantly decreased in HFD group by LOLA treatment. Meanwhile, LOLA significantly increased lean body mass, grip strength, and average muscle fiber diameter of HFD-fed mice. These findings suggest that the occurrence of NASH precedes sarcopenia in HFD mice, and the steatohepatitis-related hyperammonemia might contribute to the pathogenesis of sarcopenia. LOLA might be an effective drug for both steatohepatitis and sarcopenic obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Yang, Zhao, Xin, Li, Ren and Fan.)

Background and Aims: Nonalcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), is common in obese patients. Intragastric balloon (IGB), an obesity management tool with low complication risk, might be used in MAFLD treatment but there is still unexplained heterogeneity in results across studies., Methods: We conducted a systematic search of 152 citations published up to September 2020. Meta-analyses, stratified analyses, and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), and to identify patients most appropriate for IGB therapy., Results: Thirteen observational studies and one randomized controlled trial met the inclusion criteria (624 participants in total). In the overall estimate, IGB therapy significantly improved the serum markers change from baseline to follow-up [HOMA-IR: 1.56, 95% confidence interval (CI)=1.16-1.95; ALT: 11.53 U/L, 95% CI=7.10-15.96; AST: 6.79 U/L, 95% CI=1.69-11.90; GGT: 10.54 U/L, 95% CI=6.32-14.75]. In the stratified analysis, there were trends among participants with advanced age having less change in HOMA-IR (1.07 vs. 1.82). The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic IGB. Multivariate meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age ( p =0.0107). Furthermore, effectiveness on ALT and GGT was predicted by basal ALT ( p =0.0004) and GGT ( p =0.0026), respectively., Conclusions: IGB is effective among the serum markers of MAFLD. Younger patients had a greater decrease of HOMA-IR after IGB therapy., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

A facultatively anaerobic bacterium, strain M1531 T , was isolated from a red alga (Porphyra) at coastal water in Weihai, China. Cells of the novel strain were Gram-stain-negative, rod-shaped, motile by means of a single polar flagellum and around 0.6-0.8 × 2.0-3.0 µm in size. Optimum growth occurred at 30 °C, with 2% (w/v) NaCl and at pH 6.5-7.0. On the basis of the result of phylogenetic analysis of the 16S rRNA gene sequence, stain M1531 T had close relative with Thalassotalea euphylliae KCTC 42743 T (96.9%). Genome sequencing revealed a genome size of 4,061,950 bp, a G + C content of 39.1 mol% and four protein-coding genes related to the degradation of alginate. According to the data obtained, strain M1531 T shared ANI value below 95-96%, dDDH value below 23.8% with the closely related type species. Strain M1531 T had Q-8 as the predominant isoprenoid quinone and possessed Summed Features 3 (C 16:1 ω7c/C 16:1 ω6c), C 16:0 and Summed Features 8 (C 18:1 ω7c/C 18:1 ω6c) as the major fatty acids. The polar lipids of strain M1531 T were identified as phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid and four unidentified lipids. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic properties and genome analysis, strain M1531 T represents a novel specie of the genus Thalassotalea, for which the name Thalassotalea algicola sp. nov. is proposed. The type strain is M1531 T (= MCCC 1H00400 T  = KCTC 72865 T ).

Objective: Oxidative stress (OS) significantly correlates with cancer progression. However, targeting OS has not been considered as a therapeutic strategy in skin cutaneous melanoma (SKCM) due to a lack of systematical studies on validated biomarkers. The work presented here aimed to identify hub prognosis-associated OS genes in SKCM and generated an effective predictive model., Patients and Methods: Gene expression profiles of SKCM samples and normal skin tissues were obtained from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases to identify differentially expressed OS genes. The validation cohort was obtained from the Gene Expression Omnibus (GEO) database., Results: Thirteen hub prognosis-associated OS genes were recognized and incorporated into the prognostic risk model. Our constructed model was significantly associated with overall survival of SKCM patients as well as was shown to be associated with cancer progression. Our prognostic risk model was found to improve the accuracy of diagnostics, as shown using both TCGA and GEO cohorts. Both hub gene expression and risk score were used to generated nomograms that displayed favorable discriminatory abilities for SKCM., Conclusions: Overall, our study presents a model that may provide novel insights into the prognosis and survival of SKCM patients, as well as the development of individualized treatment therapy.

Background and Aims: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored., Methods: A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed., Results: Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK-/-) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1-/- mouse embryonic fibroblasts., Conclusions: These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

As multifunctional materials, rare-earth hexaborides (RB 6 ) display many interesting physical properties such as optical absorption, magnetic and thermionic emission. With the wide application of rare earth hexaboride and the continuous extension of its research fields, researchers have studied the synthesis of multi-rare earth hexaboride nano-powders and their thermal emission and light absorption properties. In the present work, ternary Single-phase La x Pr 1- x B 6 submicron powders are successfully synthesized using a solid-state reaction, in which lanthanum chloride (LaCl₃) and praseodymium chloride (PrCl₃) are used as rare-earth source and NaBH₄ as the boron source under continuous vacuum conditions. The reaction temperature is 1150 °C and the holding time is 2 h. The Pr doping effects on crystal structure, grain morphology, and optical absorption properties were investigated using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and ultraviolet-vis absorption measurements. The XRD patterns show that the diffraction peaks are sharp and well-defined, and no other extra impurity peaks were detected, indicating the characteristics of well-crystallized materials. It is found that all the La x Pr 1- x B 6 solid powders are of single phase. The SEM results demonstrate that the cubicshaped ternary La x Pr 1- x B 6 submicron crystals with a size of 50~200 nm are obtained. The TEM images reveal the cubic single-crystalline nature, and the FFT patterns implies the lattice fringe d = 0.416 nm which agrees well with the (100) crystal plane. The elements mapping results indicates that the Pr atoms occupied the lattice sites of LaB 6 . The optical absorption results show that the absorption valley of LaB 6 are located at 591 nm. With the increase of Pr doping contents from 0.2 to 0.8, the absorption valley moves from 596.3 nm to 612.9 nm, indicating the characteristics of visible light high transparency. The first-principle calculation results manifest that the move of the absorption valley of LaB 6 in the visible region after doping Pr is related to the decrease of kinetic energy of electrons near the Fermi plane. X-ray photoelectron spectroscopy (XPS) analysis shows that the La and Pr exist in the type of La 3+ and Pr 3+ in La x Pr 1- x B 6 . Therefore, it exists as an efficient optical absorption material. The La x Pr 1- x B 6 should open up a new route to extend the optical applications of rare-earth hexaborides.

Aim: This study aimed to explore the prognostic value of leukocyte telomere length (LTL) in patients with coronary artery disease (CAD). Materials & methods: We enrolled 366 CAD patients and 76 healthy subjects in this study. LTL was measured. All subjects were followed up for 6 months for further analysis regarding major adverse cardiac events (MACEs). Results: CAD patients had a significantly shortened LTL compared with healthy subjects (p < 0.05). The area under the curve for LTL prediction of MACEs was 0.769 (p < 0.001), with a shorter LTL being an independent predictor of MACEs (Cox proportional hazards regression, hazard ratio: 2.866; p < 0.001). Conclusion: LTL could be considered as an independent predictor of short-term MACEs in CAD.

Background: The treatment options of systemic lupus erythematosus (SLE) patients in active and inactive phases are very different clinically, and the prognosis of patients with active SLE is much worse than inactive patients. However, the present indicators for diagnosis of SLE in activity are limited and inefficient., Methods: Three hundred thirty patients with SLE were included. All patients are classified as SLEDAI (systemic lupus erythematosus disease activity index) > 4 as active and SLEDAI ≤ 4 as inactive. The linear correlation between variables was assessed by Pearson's correlation analysis. The difference between parameters in active and inactive patients was evaluated by the Mann-Whitney U test. The evaluation capacity of erythrocyte sedimenta-tion/red blood cell (ERR) and red blood cell/albumin ratio (RAR) on SLE activity was determined by bivariate regression analysis. Sensitivity and specificity are assessed by receiver operating characteristic curve (ROC)., Results: Compared with the inactive SLE, ESR (52.97 ± 35.66 vs. 32.38 ± 29.16 p < 0.001), ERR (15.40 ± 12.41 vs. 8.19 ± 8.10 p < 0.001) and RAR (0.13 ± 0.10 vs. 0.11 ± 0.20 p = 0.038) are all elevated in active SLE (52.97 ± 35.66 vs. 32.38 ±2 9.16 p < 0.001). ERR shows better correlation than RAR with ESR (p < 0.001 vs. p = 0.911). Patients with active SLE exhibited higher SLEDAI than those with inactive SLE (8.67 ± 2.67 vs. 3.27 ± 1.36, p < 0.001). According to ROC analysis, when ESR levels > 58.5 and ERR levels > 13.18, the sensitivity is 37.6% and 45.2%, the specificity is 83.0% and 83.2%., Conclusions: ESR and ERR are potential indicators for diagnosis of active and inactive SLE.

Background & Aims: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Progression from BE to cancer is associated with obesity, possibly due to increased abdominal pressure and gastroesophageal reflux disease, although this pathogenic mechanism has not been proven. We investigated whether environmental or dietary factors associated with obesity contribute to the progression of BE to EAC in mice., Methods: Tg(ED-L2-IL1RN/IL1B)#Tcw mice (a model of BE, called L2-IL1B mice) were fed a chow (control) or high-fat diet (HFD) or were crossbred with mice that express human interleukin (IL) 8 (L2-IL1B/IL8 mice). Esophageal tissues were collected and analyzed for gene expression profiles and by quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry. Organoids were established from BE tissue of mice and cultured with serum from lean or obese individuals or with neutrophils from L2-IL1B mice. Feces from mice were analyzed by 16s ribosomal RNA sequencing and compared to 16s sequencing data from patients with dysplasia or BE. L2-IL1B were mice raised in germ-free conditions., Results: L2-IL1B mice fed an HFD developed esophageal dysplasia and tumors more rapidly than mice fed the control diet; the speed of tumor development was independent of body weight. The acceleration of dysplasia by the HFD in the L2-IL1B mice was associated with a shift in the gut microbiota and an increased ratio of neutrophils to natural killer cells in esophageal tissues compared with mice fed a control diet. We observed similar differences in the microbiomes from patients with BE that progressed to EAC vs patients with BE that did not develop into cancer. Tissues from dysplasias of L2-IL1B mice fed the HFD contained increased levels of cytokines that are produced in response to CXCL1 (the functional mouse homolog of IL8, also called KC). Serum from obese patients caused organoids from L2-IL1B/IL8 mice to produce IL8. BE tissues from L2-IL1B mice fed the HFD and from L2-IL1B/IL8 mice contained increased numbers of myeloid cells and cells expressing Cxcr2 and Lgr5 messenger RNAs (epithelial progenitors) compared with mice fed control diets. BE tissues from L2-IL1B mice raised in germ-free housing had fewer progenitor cells and developed less dysplasia than in L2-IL1 mice raised under standard conditions; exposure of fecal microbiota from L2-IL1B mice fed the HFD to L2-IL1B mice fed the control diet accelerated tumor development., Conclusions: In a mouse model of BE, we found that an HFD promoted dysplasia by altering the esophageal microenvironment and gut microbiome, thereby inducing inflammation and stem cell expansion, independent of obesity., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Salmonella can cause enteric diseases in humans and a wide range of animals, and even outbreaks of foodborne illness. The aim of this study was to investigate the frequency and distribution of serovars, and antimicrobial resistance in Salmonella isolates from pigs with diarrhea in 26 provinces in China from 2014 to 2016. A total of 104 Salmonella isolates were identified and the dominant serovar was S. 4,[5],12:i:- (53.9%). All Salmonella isolates were resistant to trimethoprim-sulfamethoxazole, and many were resistant to ampicillin (80.8%) and tetracycline (76.9%). Among 104 Salmonella isolates, aac(6')-Ib-cr was the dominant plasmid-mediated quinolone resistance gene (80.8%), followed by qnrS (47.1%). The pulsed-field gel electrophoresis results suggest that the Salmonella isolates from different regions were genetically diverse, and ST34 was the most prevalent. S. 4,[5],12:i:- isolates is the widespread presence of heavy metal tolerance genes. The fact that the same sequence types were found in different regions and the high similarity coefficient of S. 4,[5],12:i:- isolates from different regions indicate the clonal expansion of the isolates, and the isolates carried various antimicrobial resistance genes. The multidrug resistant Salmonella can be widely detected in pigs, which will present a challenge for farm husbandry.

Background: Gallbladder perforation is a rare but lethal condition and its diagnosis is usually difficult and delayed. Frequently, gallbladder rupture is associated with cholecystitis, but spontaneous perforation was ever described. However, spontaneous rupture of gallbladder has never been reported in patients underwent peritoneal dialysis., Case Presentation: We report a 62-year-old man who presented with abdominal pain for 2 days to clinic. Peritoneal dialysis-related peritonitis was diagnosed initially. It was followed by spontaneous gallbladder perforation with greenish dialysate. The patient was managed successfully by antibiotic treatment and primary closure of gallbladder perforation with external drainage. He recovered from this critical condition and stayed on dialysis., Conclusions: Early diagnosis and timely surgical intervention yields a good prognosis in PD patients with gallbladder perforation. Surgical intervention and antibiotic treatment are the mainstay of treatment. Both of them should take place promptly.

Hepatocellular carcinoma (HCC) is a highly aggressive, solid malignancy that has a poor prognosis. Long non-coding RNAs (lncRNAs) have been found to be dysregulated in various cancers, including HCC. However, the molecular mechanism involving lncRNAs in HCC remains largely unknown. In this study, lncRNAs differentially expressed between HCC and corresponding non-cancerous tissue were identified by microarray analysis. A specific differentially expressed lncRNA UBE2CP3 (ubiquitin conjugating enzyme E2 C pseudogene 3) was identified. LncRNA UBE2CP3 was frequently up-regulated in HCC samples as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) experiments. Clinical data showed that high levels of lncRNA UBE2CP3 were correlated with poor prognosis in HCC patients. Functional studies demonstrated that over-expression of lncRNA UBE2CP3 promoted cell invasion and migration in vitro and in vivo . Mechanistically, enhanced expression of lncRNA UBE2CP3 increased the expression of Snail1 and N-cadherin, but decreased the expression of E-cadherin, thus promoting the process of epithelial to mesenchymal transition (EMT) and finally inducing cell invasion and migration. Furthermore, serum levels of lncRNA UBE2CP3 were increased in HCC patients and decreased after surgery. Our results suggest that lncRNA UBE2CP3 promotes the metastasis of HCC and that serum lncRNA UBE2CP3 may be a new biomarker for the diagnosis of HCC., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Aim: miR-548p is a recently identified and poorly characterized miRNA. However, its role of miR-548p in tumorigenesis and progression remains poorly understood. Here, we aimed to investigate the biofunction of miR-548p in hepatocellular carcinogenesis., Methods: The expression levels of miR-548p were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The role of miR-548p in hepatocellular carcinoma (HCC) was determined by colony formation, flow cytometry assay and nude mice xenograft experiments. miR-548p target genes were analyzed by miRNA target predication programs and verified by qRT-PCR, western blotting assay and dual-luciferase reporter assay., Results: miR-548p is repressed by hepatitis B virus X protein (HBx) in HCC tumor tissues and hepatoma cells, and inhibited cell growth by inhibiting cell proliferation and promoting cell apoptosis. miR-548p directly downregulated the expression of hepatitis B x-interacting protein (HBXIP) by binding to the 3'-untranslated region of HBXIP mRNA. Further study showed that hepatocyte nuclear factor-4a (HNF4A) promoted the expression of miR-548p and inhibited the transcription of HBXIP. HNF4A is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis, and is shown to be repressed by HBx., Conclusion: We proposed the model for HBx/HNF4A/miR-548p/HBXIP pathway that controls hepatoma cell growth and tumorigenesis of HCC. miR-548p was identified as a tumor-suppressor in HBx-associated hepatocellular carcinogenesis., (© 2015 The Japan Society of Hepatology.)

Accumulating evidence supports an important role for the hepatitis B virus x protein (HBx) in the pathogenesis of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC), but the underlying mechanisms are not entirely clear. Here, we identified a novel long noncoding RNA (lncRNA) DBH-AS1 involved in the HBx-mediated hepatocarcinogenesis. The levels of DBH-AS1 were positively correlated with hepatitis B surface antigen (HBsAg) and tumor size in HCC tissues. Functionally, transgenic expression of DBH-AS1 significantly enhanced cell proliferation and tumorigenesis, whereas short hairpin RNA knockdown of DBH-AS1 caused an inhibition of cell proliferation. Mechanistically, overexpression of DBH-AS1 induced cell cycle progression by accelerating G1/S and G2/M transition concomitantly with upregulation of CDK6, CCND1, CCNE1 and downregulation of p16, p21 and p27. We also found that enhanced DBH-AS1 expression inhibited serum starvation-induced apoptosis of HCC cells. In contrast, suppressed DBH-AS1 expression had opposite effects. Furthermore, DBH-AS1 was shown to activate MAPK pathway. We also provide evidence that DBH-AS1 could be significantly induced by HBx protein and markedly down-regulated by p53. Thus, we concluded that DBH-AS1 can be induced by HBx and inactivated by p53, and consequently promote cell proliferation and cell survival through activation of MAPK signaling in HCC. Our study suggests that DBH-AS1 acts as an oncogene for HCC.

Aims: This study explored whether surgical stress-induced glucocorticoid receptor (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in aged individuals. Inhibition of GR activation could be an effective treatment for POCD., Methods: A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 months old. Animals in control group were treated in identical manners except for laparotomy. Cognitive function was evaluated by Morris water maze and elevated plus maze. Western blot and Elisa assay were used to detect related molecules. Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation., Results: The cognitive function was impaired, and brain-derived neurotrophic factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus and elevated GR phosphorylation were found in prefrontal cortex of aged POCD mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of BDNF and cognitive dysfunction in aged mice were both rescued., Conclusion: These results presented a mechanism that surgical stress-induced GR phosphorylation contributes to POCD in aged individuals. Inhibition of GR activation and phosphorylation might be a potential treatment target of POCD., (© 2015 John Wiley & Sons Ltd.)

Conditions to prepare trans-[Ru2(dmba)4(C[triple chemical bond]CAr)2] from [Ru2(dmba)4(NO(3))2] (DMBA=N,N'-dimethylbenzamidinate) and HC[triple chemical bond]CAr were optimized; Et2NH was found to be the most effective among a number of weak bases in facilitating the product formation. Furthermore, a series of unsymmetric trans-[(ArC[triple chemical bond]C)Ru(2)(dmba)4(C[triple chemical bond]CAr')] compounds were prepared under optimized conditions, in which one or both of Ar and Ar' are donor (NMe2)-/acceptor (NO(2))-substituted phenyls. While the X-ray crystallographic studies revealed a minimal structural effect upon donor/acceptor substitution, voltammetric measurements indicated a significant influence of substituents on the energy level of frontier orbitals. In particular, placing a donor and an acceptor on the opposite ends of trans-[(ArC[triple chemical bond]C)Ru2(dmba)4(C[triple chemical bond]CAr')] moiety results in an energetic alignment of frontier orbitals that favors a directional electron flow, a necessary condition for unimolecular rectification.

Evidence has accumulated over the years supporting glutamate as the primary neurotransmitter used by hair cells in afferent cochlear neurotransmission. Besides acting on ionotropic glutamate receptors, glutamate also activates second messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs) to modulate neuronal excitability. However, it is unclear whether mGluRs participate in cochlear neurotransmission. We present evidence directly supporting a functional role for group I metabotropic glutamate receptors (mGluRIs) in spiral ganglion (SG) neurons. The presence of mGluRI and downstream G-protein subunits was demonstrated by molecular biology and immunolabeling methods. Direct activation of mGluRIs in cultured SG neurons resulted in transient increases of intracellular Ca(++) concentration and transient inward currents that gave rise to firings of multiple action potentials. These responses showed mGluRI pharmacological specificity and quickly desensitized. We next examined changes in cochlear function after noise exposure as a result of pharmacologically manipulating cochlear glutamate neurotransmission. These in vivo tests showed that blocking non-N-methyl-D-aspartic acid glutamate receptors was sufficient to eliminate compound action potentials of the auditory nerve, and pharmacologically inhibiting mGluRIs in the cochlea did not significantly affect the hearing threshold. In contrast, blocking mGluRIs lowered the amplitude of compound action potentials at louder sound levels and reduced the noise-induced temporary threshold shift. Our results suggest that although mGluRIs did not initiate fast excitatory cochlear neurotransmission, their activation contributed to the growth of excitatory responses of the cochlea. As a result, the cochlea was more resistant to noise-induced temporary hearing losses without the activation of mGluRIs in SG neurons.

Objective: To investigate the protective effect of ulinastatin on myocardium against ischemia-reperfusion injury in open heart surgery with cardiopulmonary bypass (CPB)., Methods: Twenty ASA I-II patients undergoing atrioseptopexy or surgical repair of ventricular septal defect under CPB were randomly divided into two groups of 10 patients. The patients in the ulinastatin group (U), 5 males and 5 females, aged 6.7 +/- 2.6, received ulinastatin 12,000 unit/kg, half of the dose being given intravenously 10 min before aorta cannulation and another half being added into the priming fluid. The patients in the control group (C), 6 males and 4 females, aged 5.9 +/- 2.7, received the same volume of normal saline instead of ulinastatin. Arterial blood samples were taken before CPB (T1), at release of the aortic cross-clamp (T2), 30 min after aortic release (T3), 4 h and 24 h after discontinuation of CPB (T4, T5) for determination of plasma levels of cardiac troponin I (cTnI), creatine phosphokinase (CK) and creatine phosphokinase isoenzyme (CK-MB)., Results: The CPB time, aortic cross-clamping time and duration of operation were comparable between these 2 groups. The plasma cTnI level and CK and CK-MB activities were all within normal range before CPB in both groups. In group C the plasma level of cTnI started to increase at T2, peaked at T4 and started to decrease at T5. In group U the plasma levels of cTnI at T3 and T4 were significantly higher than the baseline value (both P<0.01) and returned to the baseline value at T5. The plasma cTnI levels at T(3-5) were significantly lower in group U than in group C (all P<0.01). The plasma CK and CK-MB activities increased significantly at T(2-5) in both groups (all P<0.01). There was no significant difference in plasma CK and CK-MB activity at T(2-4) between the two groups, but at T5 their activities were significantly lower in group U than in group C (P<0.05). The rate of spontaneous recovery of heart beat without defibrillation was higher in group U (8/10) than in group C (4/10) (P<0.05). The drainage volume during the 24 hours after operation was greater in group C than in group U (P<0.05)., Conclusion: Ulinastatin effectively protects myocardium from ischemia-reperfusion injury during open heart surgery with CPB.

Previous data suggest that regulation of cochlear blood flow (CBF) may be abnormal in the hydropic guinea pig. The purpose of this study was to employ the technique of anterior inferior cerebellar artery (AICA) occlusion to measure CBF autoregulation in experimental endolymphatic hydrops. This study also addresses the role of the cochlear sympathetic neural innervation and nitric oxide in CBF regulation with hydrops. In anesthetized guinea pigs, CBF was measured with a laser Doppler flowmeter probe while the AICA was intermittently occluded with a microvascular occluder. The CBF response was measured in normal, 6-week, and 12-week chronically hydropic animals. The gain factors (0 = no autoregulation, 1 = complete autoregulation) for 1-min occlusion were 0.95 +/- 0.16 (control), 0.77 +/- 0.28 (6 week, P = 0.164), and 0.67 +/- 0.25 (12 week, P = 0.037). NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was infused intravenously to assess basal nitric oxide (an endogenous vasodilator) production in the hydropic ear. With infusion of L-NAME, CBF was reduced by 9.16 +/- 11%, 10.7 +/- 10% (P = 0.87), and 16.6 +/- 18% (P = 0.95), in the control, 6-week, and 12-week animals, respectively. In a separate group of 12-week hydropic animals, the left superior cervical ganglion (SCG) was anesthetized with lidocaine, and AICA occlusions were performed pre- and post-blockade. Prior to blocking the SCG, the gain was 0.712 +/- 0.02 and afterwards 0.708 +/- 0.051 (P = 0.93). The above results show that there was a statistically significant reduction in CBF autoregulation in the 12-week hydropic animals. There was no difference in basal nitric oxide production in normal versus hydropic animals nor was there a change in autoregulation following blockade of the SCG. These data provide clear evidence for reduced CBF autoregulation in experimental endolymphatic hydrops.

Laser Doppler flowmetry was used to assess cochlear blood flow (CBF) in the hydropic ear in four experiments. 1) The increase in CBF elicited by local electrical stimulation of the cochlea in the hydropic ear was compared to that observed in normal controls. The magnitude of the evoked CBF change was reduced by approximately 30% in the hydropic ear compared to the normal ear. 2) The reduction in CBF evoked by direct electrical stimulation of the superior cervical ganglion was reduced by approximately one third in the hydropic ear compared to a normal ear. 3) Rhythmic (flux motion or vasomotion) variations in CBF, observed in association with lower blood pressure and thought to extend the autoregulatory range in an organ system, were reduced or eliminated in the hydropic ear. 4) The autoregulatory response to a decreased perfusion pressure, produced by decreased cardiac output, was clearly reduced relative to control in the hydropic ear. These findings represent the first report of significant CBF changes with hydrops. They are consistent with reports of increased sensitivity of the hydropic ear to trauma and stress and may be relevant considerations in the treatment of hydrops in humans.

This article reviews current studies on inner ear blood flow, discusses their relevance to the maintenance of normal homeostasis of the inner ear, reports for the first time clear changes in fundamental properties of cochlear blood flow in the chronic hydropic ear, and describes the potential of applying laser Doppler flowmetry technology to the measurement of inner ear blood flow in human beings. Studies of the guinea pig in which perfusion pressure is varied demonstrate a broad range of autoregulatory capabilities of the inner ear vasculature. Gain factors range from 0.76 and higher for recovery for less than 1 minute of modified perfusion pressure. This is significantly greater than reports obtained for brain autoregulation. In a series of four investigations of cochlear blood flow in the hydropic ear in guinea pigs, a decreased responsiveness to electrical stimulation and direct stimulation of the superior cervical ganglia was found, indicating a change in sympathetic control of cochlear tone. Reduced vasomotion was observed, and autoregulatory capabilities were reduced. In human investigations, changes in cochlear blood flow were demonstrated with direct electrical stimulation of the round window and warm water irrigation of the ear canal, but not with carbogen breathing. Increased cochlear blood flow was observed with increased systemic blood pressure, and a remarkable decrease in cochlear blood flow was observed with the application of 1:10,000 epinephrine to the round window. These observations indicate the potential for development of laser Doppler flowmetry technology in the diagnosis and treatment of inner ear vascular disorders, and the animal investigations suggest that changes may occur in the chronic hydropic ear that compromise autoregulation and thus increase the sensitivity of the hydropic ear to other stress factors. Treatments can be found to modify such changes in vascular tone.

1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal input to the cochlea comes through the perivascular sympathetic plexus from the cervical sympathetic chain and along the vestibular nerve (VN) from the periolivary area of the brainstem. Both of these neuronal systems are distributed topographically in the cochlea. 2. In order to study the neural origins of ES-evoked CBF increase, laser Doppler flowmetry was used to test the following hypotheses. (a) The response is regional, that is, limited to the area of the cochlea stimulated. To test this we performed differential ES of the cochlear turns. CBF was measured from either the third or the first turn. (b) The response is mediated via autonomic receptors within the cochlea. To study this, we applied atropine, succinylcholine and idazoxan locally to the cochlea. (c) The response is influenced by neuronal input via the sympathetic cervical chain (SC) and components of the VN. We stimulated and sectioned the SC, and sectioned the VN, to test this hypothesis. 3. We observed that the CBF response was topographically restricted to the stimulated region. Locally applied muscarinic or nicotinic antagonists (atropine and succinylcholine respectively) did not affect the response. However, local idazoxan (an alpha 2-blocker) eliminated the response. Locally applied adrenaline and SC stimulation modified the dynamic range of the response. SC sectioning enhanced the responsiveness of the cochlear vasculature to ES. The VN section caused a temporary decrease in CBF and elimination of the ES-evoked CBF response. 4. We conclude that the release of dilating agents is topographical with respect to ES current flow, the ES-evoked CBF increase is peripherally mediated via alpha 2-receptors, and the response is influenced by input via the SC. The elimination of the response by VN sectioning proximal to the brainstem indicated that fibres of the VN mediate the CBF increase during direct cochlear ES. The data suggest that these fibres may be the efferent limb of a neural loop involved with the regulation of CBF. Such a system could provide a mechanism for the rapid increase in CBF with organ stress.

Vasomotion, as a fundamental phenomenon of microvessels, exists in the cochlea of guinea pig. In the current study, the vasomotion and its relation to arterial pressure reduction was studied in the guinea pig cochlea, using laser Doppler flowmetry (LDF). Blood pressure (BP) in 25 guinea pigs was manipulated by a mechanical occluder placed around the descending aorta or the inferior vena cava. Before thoracotomy and artificial respiration, BP was 55.5 +/- 10.9 mmHg and no flux motion occurred. Vasomotion became evident when BP was significantly lower (28.2 +/- 7.2 mmHg) than the mean BP after thoracotomy (37.3 +/- 8.3 mmHg) (t = 4.1536, p < 0.05). Vasomotion appeared during both continuous hypotension and brief BP decreases caused by mechanical occlusion. During periods of continuous flux motion, both increase and decrease in BP could weaken or abolish it. The pressure provoking the vasomotion was different for each animal but the pressure range for a given animal was relatively stable. Mean frequency and amplitude of flux motion were 3.8 +/- 0.6 cycles per min and 20.8 +/- 7.1% of the baseline. A negative linear relationship was found between amplitude and frequency. Oscillations of LDF signal indicate that there is a synchronization of contraction and relaxation of cochlear microvessels or of the larger supplying vessels to the cochlea. Manipulation of BP possibly initiates the fluctuating change in vascular tone by influencing the activity of pacemaker or feedback mechanisms of cochlear vascular smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Although progress has been made in the study of cochlear blood flow (CBF) regulation since laser Doppler flowmetry (LDF) was introduced, cochlear vasomotion has not been investigated. Therefore, the primary objective of this study was to determine if oscillatory fluctuations of CBF could be provoked. Guinea pigs were anesthetized with diazepam (5 mg/kg) and fentanyl (0.32 mg/kg). Blood pressure (BP) was recorded from a carotid artery cannula. The cochlea and pons cerebellum were ventrally exposed; the bilateral CBF and brain blood flow (BBF) or skin blood flow (SBF) were monitored by LDF. After administration of phentolamine (0.25-0.75 mg/kg, i.v.), ipsilateral CBF in 7 of 16 animals showed a 2-5 min episode of oscillation. During artificial hyperventilation, continuous oscillation of CBF was recorded (the flux motion frequency was 3.5 +/- 0.5 cycles per min and its amplitude 25.8 +/- 5.6% from baseline). The time-dependent flux change (the waveform) was the same throughout a single cochlea but different between cochleae of the same animal. Compared to BBF, CBF vasomotion frequency was lower, and amplitude larger. SBF exhibited no such motion. Flux motion could be eliminated by inhalation of pure oxygen or 5% CO2 in oxygen or by the smooth muscle relaxants, papaverine and hydralazine. Phentolamine-induced vasomotion may be due to a hypotensive perfusion pressure, and hyperventilation-enhanced vasomotion may be caused by changing blood gas concentrations and by hormonal or neuronal activity. Oxygen and CO2 inhalation slightly increased BP and this change in perfusion pressure was probably associated with weakened vasomotion.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been proposed that cochlear blood flow (CBF) is controlled in part by the sympathetic nervous system. In the present study the effect of electrical stimulation of the superior cervical ganglion (SCG) on CBF in guinea pigs was investigated using laser Doppler flowmetry (LDF). Animals were anesthetized with diazepam and fentanyl and the SCG was exposed. A custom-designed bipolar cuff electrode was fixed around the ganglion and 1 ms biphasic current pulses were injected at 0.15 mA to 1.5 mA, 6 Hz. Bilateral CBF was monitored, while the ganglion was stimulated for 3 or 5 min before and after the ascending sympathetic trunk and nerve branches from SCG were sectioned. Electrical stimulation of 0.5 mA caused the ipsilateral CBF (CBFi) to decrease 11.7% +/- 1.3 from the baseline (BL), while the contralateral CBF (CBFc) increased slightly due to the change in systemic blood pressure (BP). A linear relation was observed between the level of current stimulation and evoked reduction in CBF. Cervical sympathetic trunk section (between the SCG and the middle cervical ganglion) did not influence the pattern or the amplitude of CBF change in response to electrical stimulation of SCG. Sectioning the efferent fibers of the medial inferior and medial superior branch of the SCG only minimally reduced the amplitude of the CBF decrease evoked by electrical stimulation. However, sectioning the superior lateral branch abolished this decrease.(ABSTRACT TRUNCATED AT 250 WORDS)