Deferoxamine-Loaded Injectable Chitosan-Grafted Chlorogenic Acid/Oxidized Hyaluronic Acid Hybrid Hydrogel with Antibacterial, Anti-inflammatory, and Angiogenesis-Promoting Properties for Diabetic Wound Repair.

Diabetic chronic wounds are notoriously difficult to heal as a result of their susceptibility to infection. To address this issue, we constructed an innovated and adaptable solution in the form of injectable chitosan (CS) hydrogel, denoted as CCOD, with enhanced antibacterial and anti-inflammatory properties. This hydrogel is created through a Schiff base reaction that combines chitosan-grafted chlorogenic acid (CS-CGA) and oxidized hyaluronic acid (OHA) with deferoxamine (DFO) as a model drug. The combination of CS and CGA has demonstrated excellent antibacterial and anti-inflammatory properties, while grafting played a pivotal role in making these positive effects stable. These unique features make it possible to customize injectable hydrogel and fit any wound shape, allowing for more effective and personalized treatment of complex bacterial infections. Furthermore, the hydrogel system is not only effective against inflammation and bacterial infections but also possesses antioxidant and angiogenic abilities, making it an ideal solution for the repair of chronic wounds that have been previously thought of as unmanageable.

Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis.

The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs-induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS-NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 µg/day). Results showed that inhaled PS-NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time-dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-ß, α-SMA, and Col1a1 identified that inhaled PS-NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that ferroptosis was involved in PS-NPs-induced liver hepatotoxicity, and key features of ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of ferroptosis in PS-NPs-induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS-NPs on the liver, identified that continuous inhaled PS-NPs could cause liver injury and fibrosis, and PS-NPs- ferroptosis provided a novel mechanistic explanation.

Blood FOLR3 methylation dysregulations and heterogeneity in non-small lung cancer highlight its strong associations with lung squamous carcinoma.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancers. Early detection is crucial to reduce lung cancer-related mortality. Aberrant DNA methylation occurs early during carcinogenesis and can be detected in blood. It is essential to investigate the dysregulated blood methylation markers for early diagnosis of NSCLC. METHODS: NSCLC-associated methylation gene folate receptor gamma (FOLR3) was selected from an Illumina 850K array analysis of peripheral blood samples. Mass spectrometry was used for validation in two independent case-control studies (validation I: n = 2548; validation II: n = 3866). Patients with lung squamous carcinoma (LUSC) or lung adenocarcinoma (LUAD), normal controls (NCs) and benign pulmonary nodule (BPN) cases were included. FOLR3 methylations were compared among different populations. Their associations with NSCLC clinical features were investigated. Receiver operating characteristic analyses, Kruskal-Wallis test, Wilcoxon test, logistics regression analysis and nomogram analysis were performed. RESULTS: Two CpG sites (CpG_1 and CpG_2) of FOLR3 was significantly lower methylated in NSCLC patients than NCs in the discovery round. In the two validations, both LUSC and LUAD patients presented significant FOLR3 hypomethylations. LUSC patients were highlighted to have significantly lower methylation levels of CpG_1 and CpG_2 than BPN cases and LUAD patients. Both in the two validations, CpG_1 methylation and CpG_2 methylation could discriminate LUSC from NCs well, with areas under the curve (AUCs) of 0.818 and 0.832 in validation I, and 0.789 and 0.780 in validation II. They could also differentiate LUAD from NCs, but with lower efficiency. CpG_1 and CpG_2 methylations could also discriminate LUSC from BPNs well individually in the two validations. With the combined dataset of two validations, the independent associations of age, gender, and FOLR3 methylation with LUSC and LUAD risk were shown and the age-gender-CpG_1 signature could discriminate LUSC and LUAD from NCs and BPNs, with higher efficiency for LUSC. CONCLUSIONS: Blood-based FOLR3 hypomethylation was shown in LUSC and LUAD. FOLR3 methylation heterogeneity between LUSC and LUAD highlighted its stronger associations with LUSC. FOLR3 methylation and the age-gender-CpG_1 signature might be novel diagnostic markers for the early detection of NSCLC, especially for LUSC.

Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration.

The weak regeneration ability of chondrocytes is one of the main reasons that limit the therapeutic effect of clinical cartilage injury. Injectable hydrogels are potential scaffolds for cartilage tissue engineering with advantages such as minimally invasive surgery, porous structure, and drug sustained-release ability. At present, many biomaterials have been developed for the repair of deep cartilage defects. However, cartilage injury often begins on the surface, which requires us to propose a treatment strategy suitable for superficial cartilage injury repair. In this study, we fabricated a biomimetic injectable hydrogel based on methacrylate-modified silk fibroin (SilMA) embedded with kartogenin (KGN). The SilMA/KGN hydrogels have good biohistocompatibility and the ability to promote cartilage differentiation. In addition, SEM results show that it has a porous structure conducive to cell adhesion and proliferation. Most importantly, it has demonstrated remarkable superficial cartilage repair ability in vivo, showing potential in cartilage tissue engineering.

Adaptive Aromaticity in 18e Metallapentalenes.

Complexes with aromaticity in both the lowest singlet state (S0) and the lowest triplet state (T1) (denoted as adaptive aromaticity) are rare because according to Hückel's and Baird's rules, a species could be aromatic in either the S0 or T1 state in most cases. Thus, it is particularly challenging to design species with adaptive aromaticity. Previous reports on adaptive aromaticity were mainly focused on 16e metallapentalenes. Here, we demonstrate that 18e metallapentalenes could possess adaptive aromaticity supported by a set of aromaticity indices when the nitrido and imido ligands are introduced via density functional theory calculations. Further investigation suggests that the metal-carbon bond strength plays an important role in the S0 state aromaticity and the T1 state aromaticity could be attributed to spin electron localization. All these findings could be useful for the development of metallaaromatic chemistry.

Autoantibodies of inflammatory cytokines as serum biomarkers in OSA patients.

As many as 90% of patients with obstructive sleep apnea (OSA) may be undiagnosed. It is necessary to explore the potential value of autoantibodies against CRP, IL-6, IL-8 and TNF-α in the diagnosis of OSA. ELISA was performed to detect the level of autoantibodies against CRP, IL-6, IL-8 and TNF-α in sera from 264 OSA patients and 231 normal controls (NCs). The expression level of autoantibodies against CRP, IL-6 and IL-8 in OSA were significantly higher than that in NC while the level of anti-TNF-α was lower in OSA than that in NC. The per SD increment of anti-CRP, anti-IL-6 and anti-IL-8 autoantibodies were significantly associated with a 430%, 100% and 31% higher risk for OSA, respectively. The AUC of anti-CRP was 0.808 (95% CI: 0.771-0.845) when comparing OSA with NC, while the AUC increased to 0.876 (95% CI: 0.846-0.906) combining four autoantibodies. For discrimination of severe OSA versus NC and non-severe OSA versus NC, the AUC for four autoantibodies combination was 0.885 (95% CI: 0.851-0.918) and 0.876 (95% CI: 0.842-0.913). This study revealed the association between autoantibodies against inflammatory factors and OSA, and the combination of autoantibodies against CRP, IL-6, IL-8 and TNF-α may function as novel biomarker for monitoring the presence of OSA.

Integrated microbiome-metabolome-genome axis data of Laiwu and Lulai pigs.

Excessive fat deposition can trigger metabolic diseases, and it is crucial to identify factors that can break the link between fat deposition and metabolic diseases. Healthy obese Laiwu pigs (LW) are high in fat content but resistant to metabolic diseases. In this study, we compared the fecal microbiome, fecal and blood metabolome, and genome of LW and Lulai pigs (LU) to identify factors that can block the link between fat deposition and metabolic diseases. Our results show significant differences in Spirochetes and Treponema, which are involved in carbohydrate metabolism, between LW and LU. The fecal and blood metabolome composition was similar, and some anti-metabolic disease components of blood metabolites were different between the two breeds of pigs. The predicted differential RNA is mainly enriched in lipid metabolism and glucose metabolism, which is consistent with the functions of differential microbiota and metabolites. The down-regulated gene RGP1 is strongly negatively correlated with Treponema. Our omics data would provide valuable resources for further scientific research on healthy obesity in both human and porcine.

A remarkably diverse and well-organized virus community in a filter-feeding oyster.

BACKGROUND: Viruses play critical roles in the marine environment because of their interactions with an extremely broad range of potential hosts. Many studies of viruses in seawater have been published, but viruses that inhabit marine animals have been largely neglected. Oysters are keystone species in coastal ecosystems, yet as filter-feeding bivalves with very large roosting numbers and species co-habitation, it is not clear what role they play in marine virus transmission and coastal microbiome regulation. RESULTS: Here, we report a Dataset of Oyster Virome (DOV) that contains 728,784 nonredundant viral operational taxonomic unit contigs (≥ 800 bp) and 3473 high-quality viral genomes, enabling the first comprehensive overview of both DNA and RNA viral communities in the oyster Crassostrea hongkongensis. We discovered tremendous diversity among novel viruses that inhabit this oyster using multiple approaches, including reads recruitment, viral operational taxonomic units, and high-quality virus genomes. Our results show that these viruses are very different from viruses in the oceans or other habitats. In particular, the high diversity of novel circoviruses that we found in the oysters indicates that oysters may be potential hotspots for circoviruses. Notably, the viruses that were enriched in oysters are not random but are well-organized communities that can respond to changes in the health state of the host and the external environment at both compositional and functional levels. CONCLUSIONS: In this study, we generated a first "knowledge landscape" of the oyster virome, which has increased the number of known oyster-related viruses by tens of thousands. Our results suggest that oysters provide a unique habitat that is different from that of seawater, and highlight the importance of filter-feeding bivalves for marine virus exploration as well as their essential but still invisible roles in regulating marine ecosystems. Video Abstract.

Association between nontraditional lipid profiles and the severity of obstructive sleep apnea: A retrospective study.

BACKGROUND: Due to the significant role of dyslipidemia, cardiovascular diseases (CVDs) are very common in obstructive sleep apnea (OSA). Nontraditional lipid indices are considered to be a better predictive index for cardiovascular risk. Nevertheless, the association between nontraditional lipid profiles and the severity of OSA is not clear. METHODS: A retrospective study was proceeded on 635 patients. Subjects were diagnosed with OSA through polysomnography (PSG). The association between severe OSA and nontraditional lipid profiles [triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio, total cholesterol (TC)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C), atherogenic index (AI), and lipoprotein combine index (LCI)] was examined by utilizing the restricted cubic spline and multivariate logistic regression analysis. RESULTS: All nontraditional lipid indices had positive relationships with the severity of OSA. By multivariable adjustment, the per SD increment of the TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI were significantly associated with 88%, 50%, 42%, 40%, 50%, and 125% higher risk for severe OSA respectively. Compared with the lowest tertiles, the adjusted ORs (95% CI) were 2.42 (1.57-3.75), 2.39 (1.53-3.73), 2.35 (1.52-3.64), 1.86 (1.21-2.86), 2.39 (1.53-3.73), and 2.23 (1.43-3.48) for the top tertiles of TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI respectively. CONCLUSION: All nontraditional lipid indices had positive relationship with the severity of OSA. In addition, TG/HDL-C, TC/HDL-C, and AI had better performance than the other nontraditional lipid indices for predicting severe OSA. These findings could help to determine the risk of cardiovascular diseases and improve the dyslipidemia management of OSA patients.

Tomato based gelatin methacryloyl hydrogel as an effective natural and low-cost scaffold for accelerative wound healing.

Oxidative stress and infection are the main reasons for postponement of wound healing rate. They can potentially lead to serious inflammation and eventually lead to a longer and more painful recovery phase. Although wound dressings based on synthetic materials with antioxidative property have been proved to exhibit remarkable effect in controlling ROS level and improving wound healing, issues, such as high cost in raw materials, complicated procedures, usage of various toxic additives, and potential allergies, have significantly confined further clinical applications. In this study, a novel type of tissue engineering scaffold, based on tomatoes (Solanum lycopersicon) and gelatin methacryloyl (GelMA), was prepared via facile lyophilization and photo cross-link method (SL/GelMA). By taking advantages of various antioxidative components, such as carotenoids, flavonoids, phenolic acids, vitamin E, and vitamin C in tomatoes, SL/GelMA can effectively regulate ROS level, relieve the oxidative stress in wound bed, promote cell migration and angiogenesis, contribute to collagen deposition, and thus accelerate the rate of wound enclosure. Along with its high biocompatibility and low allergic potential, we believe that the food-derived wound dressing with facile preparation method, easy accessibility, and high cost-effectiveness can be translated for clinical treatments of various chronic wounds.

Novel blood-based FUT7 DNA methylation is associated with lung cancer: especially for lung squamous cell carcinoma.

BACKGROUND: The death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation to detect LC. METHODS: Mass spectrometry assays were conducted to measure DNA methylation levels of seven CpG sites within FUT7 gene in the peripheral blood of 428 patients with LC, 233 patients with benign pulmonary nodule (BPN) and 862 normal controls (NC). The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using per SD change and tertiles analyses by logistic regression. The predictive ability of the seven FUT7 CpG sites and risk factors were evaluated by receiver operating characteristic curve (ROC). RESULTS: The methylation levels of seven CpG sites of FUT7 in LC were significantly lower than that in NC (P < 0.05). The per SD decrement of methylation level in CpG_1-7 was significantly associated with 65%, 38%, 59%, 46%, 23%, 20% and 68% higher risk for LC versus NC, respectively, and the adjusted ORs (95% CI) were 2.92 (2.17-3.96), 1.76 (1.29-2.38), 2.83 (2.09-3.82), 3.00 (2.17-4.16), 1.81 (1.35-2.43), 1.48 (1.11-1.97) and 3.04 (2.23-4.16) for the lowest tertiles of methylation level in CpG_1-7 compared with the top tertiles, respectively. The area under the curve (AUC) of FUT7_CpG_1-7 was 0.659 (CI 0.626-0.693), 0.792 (CI 0.736-0.848) and 0.729 (CI 0.665-0.792) in distinguishing LC versus NC, LUSC versus NC and LUSC versus BPN. CONCLUSIONS: Our study revealed an association between FUT7 hypomethylation and LC, especially for LUSC, which provides novel support for the blood-based methylation signatures as potential marker for assessing lung cancer risk.

Relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China.

BACKGROUND: With an increasing incidence of obesity, the relationship between obesity and body image has become a hot research topic worldwide. From high school to university, young people experience changes in their social environment. University students have a high incidence of eating disorders and insufficient physical activity. The purpose of this study was to explore the relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China. METHODS: In total, 1296 university students aged 18-23 years were recruited for this study. The participants completed anthropometric measurements, the Physical Activity Rating scale-3 (PARS-3), and the Chinese-Dutch Eating Behavior Questionnaire (C-DEBQ). The ideal weight and silhouette were reported by university students using a questionnaire. RESULTS: Compared with men, young women had a higher level of body dissatisfaction. For men, body mass index (BMI; ß = 0.76, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.10, P <  0.01) were the significant factors predictive of body dissatisfaction. For women, BMI (ß = 0.57, P <  0.01), muscle mass (ß = 0.12, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.09, P <  0.01) were the significant factors predictive of body dissatisfaction. CONCLUSIONS: University students with high body dissatisfaction had lower physical activity scores and higher restrained eating scores. The data presented here highlight the impact of university students' body dissatisfaction on physical activity deficiency and disordered eating behaviors in China.

Genomic Signatures Reveal Breeding Effects of Lulai Pigs.

In Chinese pig populations in which crossbreeding is used, these animals show a level of weakness compared with their original purebred ancestors. For instance, in the Lulai pig, a newly developed Chinese breed that is raised on the basis of the Laiwu pig (a Chinese indigenous breed with exceptionally high intramuscular fat content) and the Yorkshire pig using a method of systematic crossbreeding, both their market acceptance and performance are inferior. To reveal the practical role of these admixed breeds and traditional systematic crossbreeding methods at the genomic level, we explored population structure, genetic signatures, and introgression. We conducted this study based on the SNP chip data of 381 Lulai pigs, 182 Laiwu pigs, and 127 Yorkshires, which showed deficient genome coverage during our study. Therefore, we further selected the Genotyping by Genome Reducing and Sequencing (GGRS) method, which has a high density and suitable genome coverage as a supplement. We applied the GGRS data of 38 Lulai pigs, 75 Laiwu pigs, and 75 Yorkshires. In terms of the SNP chip data, by Fst analysis, we detected 782 significantly different genes between Lulai pigs and Yorkshires, including 3 major genes associated with growth (LEPR) and meat quality (SCD and TBC1D1), and we detected 426 significantly different genes between Lulai pigs and Laiwu pigs. With rIBD, we detected 12 genomic regions that included 182 genes that Yorkshires introgressed to Lulai pigs, and we detected 27 genomic regions that included 229 genes with a major gene (SCD) that Laiwu pigs introgressed to Lulai pigs. Regarding the GGRS data, we detected 601 significantly different genes between Lulai pigs and Yorkshires by Fst analysis, including 3 major genes associated with growth and fat deposits (IGF2 and FTO) and with hair color (KIT), and we detected 634 significantly different genes between Lulai pigs and Laiwu pigs, including 3 major genes related to their body composition (MYPN), hair color (KIT), and ear size (PPARD). By rIBD, we detected 94 deep sections that included 363 genes that Yorkshires introgressed to Lulai pigs, and we detected 149 deep sections that included 727 genes with a major gene (ESR1) that Laiwu pigs introgressed to Lulai pigs. Altogether, this study provides both insight into the molecular background of synthesized breeds of Lulai pigs and a reference for the evaluation of systematic crossbreeding in China.

Runs of Homozygosity Revealed Reproductive Traits of Hu Sheep.

Hu sheep, a famous breed in the Taihu Basin, has the advantages of non-seasonal estrus, multiple fetuses, coarse feeding tolerance, and suitability for house feeding. Runs of homozygosity (ROHs) were found to be an effective tool to detect the animal population structure and economic traits. The detection of ROHs is beneficial for reducing the incidence of inbreeding as well as identifying harmful variants in the genome. However, there is a lack of systemic reports on ruminants in previous studies of ROHs. Here, we sequenced 108 Hu sheep, detected ROHs in Hu sheep to calculate their inbreeding coefficient, and selected genes of Hu sheep breeds within the ROH islands which are relevant to agricultural economic characteristics. Then, we compared the characteristics of the occurrences of SNPs between Hu sheep and other sheep breeds, and also investigated the distribution of the frequencies of SNPs within specific gene regions of Hu sheep breeds to select their breed-specific genes. Furthermore, we performed a comparative genome and transcriptome analysis in human and sheep breeds to identify important reproduction-related genes. In this way, we found some significant SNPs, and mapped these with a set of interesting candidate genes which are related to the productive value of livestock (FGF9, BMPR1B, EFNB3, MICU2, GFRA3), healthy characteristics (LGSN, EPHA5, ALOX15B), and breed specificity (FGF9, SAP18, MICU2). These results in our study describe various production traits of Hu sheep from a genetic perspective, and provide insights into the genetic management and complementary understanding of Hu sheep.

Hydrogel Development for Rotator Cuff Repair.

Rotator cuff tears (RCTs) are common in shoulder disease and disability. Despite significant advances in surgical repair techniques, 20-70% of patients still have postoperative rotator cuff dysfunction. These functional defects may be related to retear or rotator cuff quality deterioration due to tendon retraction and scar tissue at the repair site. As an effective delivery system, hydrogel scaffolds may improve the healing of RCTs and be a useful treatment for irreparable rotator cuff injuries. Although many studies have tested this hypothesis, most are limited to laboratory animal experiments. This review summarizes differences in hydrogel scaffold construction, active ingredients, and application methods in recent research. Efforts to determine the indications of hydrogel scaffolds (with different constructions and cargos) for various types of RCTs, as well as the effectiveness and reliability of application methods and devices, are also discussed.

Blocking TGF-ß Expression Attenuates Tumor Growth in Lung Cancers, Potentially Mediated by Skewing Development of Neutrophils.

In the tumor microenvironment (TME), cells secrete a cytokine known as transforming growth factor-ß (TGF-ß), which polarizes tumor-associated neutrophils (TANs) towards a protumor phenotype. In this work, C57BL/6 mice with TGF-ß1 gene knocked out selectively in myofibroblasts receive orthotopic implantation of Lewis lung carcinoma (LLC). Then, TANs' differentiation and tumor growth are studied both in vivo and in vitro, to examine the potential effects of TGF-ß levels in TME on neutrophil polarization and cancer progression. Possible results are anticipated and discussed from various aspects. Though tumor suppression via inhibition of TGF-ß signaling has been widely studied in this field, this study is the first to present a detailed experimental design for evaluating the potential antitumor effects of blocking TGF-ß expression. This work provides a creative approach for cancer treatment targeting specific cytokines, and the experimental design presented here may apply to future research on other cytokines, promoting the development of novel cancer-treating strategies.

Role of raphe magnus 5-HT1A receptor in increased ventilatory responses induced by intermittent hypoxia in rats.

BACKGROUND: Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia. METHODS: Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia. RESULTS: Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon. CONCLUSIONS: The results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.

Effect of Continuous Positive Airway Pressure on Chronic Cough in Patients with Obstructive Sleep Apnea and Concomitant Gastroesophageal Reflux.

BACKGROUND: Obstructive sleep apnea (OSA) and/or gastroesophageal reflux (GER) may be the contributors to chronic cough in patients with OSA and concomitant GER. This study aimed to explore whether continuous positive airway pressure (CPAP), antireflux treatment and lifestyle modifications improve chronic cough in patients with OSA and concomitant GER. METHODS: Patients with OSA and concomitant GER who also experienced chronic cough were enrolled, and were divided into two groups. Patients who were treated with general treatment (antireflux treatment and lifestyle modifications) as the control group, and patients who were treated with CPAP and general treatment as the treatment group. Effects of different treatments on chronic cough were assessed, and the association among chronic cough, GER and OSA was evaluated by Pearson's correlation analysis. RESULTS: The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale were better in the treatment group after 1 week of treatment; further, the improvement became stronger with the duration of therapy. The gastroesophageal reflux disease questionnaire, visual analog scale (VAS) for cough, and daytime and nighttime cough symptom scores significantly improved in both groups after treatment, whereas this improvement was more significant in the treatment group. Significant associations between the apnea-hypopnea index (AHI) and VAS, weak acid reflux and VAS, and weak acid reflux and AHI were observed. CONCLUSION: CPAP improved the symptoms of chronic cough and GER in patients with OSA and concomitant GER. AHI and weak acid reflux may be important factors affecting the therapeutic effect of chronic cough in patients with OSA and concomitant GER.