TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 may participate in the process of the coexistence of asthma and OSA.

OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.

Multi-omics reveals 2-bromo-4,6-dinitroaniline (BDNA)-induced hepatotoxicity and the role of the gut-liver axis in rats.

2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100 mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e.g., HSI, ALT, and ARG1), and induced systemic inflammation (e.g., G-CSF, MIP-2, RANTES, and VEGF), dyslipidemia (e.g., TC and TG), and bile acid (BA) synthesis (e.g., CA, GCA, and GDCA). Transcriptomic and metabolomic analyses revealed broad perturbations in gene transcripts and metabolites involved in the representative pathways of liver inflammation (e.g., Hmox1, Spi1, L-methionine, valproic acid, and choline), steatosis (e.g., Nr0b2, Cyp1a1, Cyp1a2, Dusp1, Plin3, arachidonic acid, linoleic acid, and palmitic acid), and cholestasis (e.g., FXR/Nr1h4, Cdkn1a, Cyp7a1, and bilirubin). Microbiome analysis revealed reduced relative abundances of beneficial gut microbial taxa (e.g., Ruminococcaceae and Akkermansia muciniphila), which further contributed to the inflammatory response, lipid accumulation, and BA synthesis in the enterohepatic circulation. The observed effect concentrations here were comparable to the highly contaminated wastewaters, showcasing BDNA's hepatotoxic effects at environmentally relevant concentrations. These results shed light on the biomolecular mechanism and important role of the gut-liver axis underpinning BDNA-induced cholestatic liver disorders in vivo.

Top 100 influential manuscripts in obstructive sleep apnea: a bibliometric analysis.

OBJECTIVE: This study aimed to explore the characteristics of the top 100 influential manuscripts on obstructive sleep apnea (OSA). METHODS: All manuscripts in English were searched from the Thomson Reuters Web of Science database by using OSA-related terms and ranked based on citation frequency. The top 100 influential manuscripts were selected and further analyzed by author, subject, journal, year of publication, country of origin, and institution. RESULTS: A total of 42,878 manuscripts were searched from the Web of Science. The top 100 influential manuscripts were published from 2005 to 2017, with a total citation frequency of 38,463 and a median citation frequency of 303 (range: from 210 to 2, 707). The American Journal of Respiratory and Critical Care Medicine published the largest number of manuscripts from the top 100 (n = 18; 5340 citations), followed by Sleep (n = 11; 3516 citations) and Chest (n = 7; 1784 citations). The most cited manuscript (Marin, J.M et al., Lancet 2005; 2707 citations) mainly analyzed long-term cardiovascular outcomes in men with OSA with/without continuous positive airway pressure. The most prevalent subject was associated diseases (n = 41), followed by treatments (n = 40). Most of the manuscripts were original articles (n = 63) based on observational clinical studies and published from American institutions (n = 60). CONCLUSIONS: Our study identified the top 100 influential manuscripts on OSA and provides insights into the characteristics of the most highly cited manuscripts to improve our understanding and management of OSA.

The signal intensity characteristics of normal bone marrow in diffusion weighted imaging at various menstrual status women.

PURPOSE: Diffuse hyperintensities of the bone marrow in whole-body diffusion-weighted (DW) imaging (DWI) have been encountered more frequently in females aged 21-50 compared to elder females or men. Therefore, we aimed to visually evaluate DWI among pre-, peri- and postmenopausal women and to verify whether it correlates also quantitatively with hormonal status. METHOD: The prospective study was approved by our institutional review board and informed consent was obtained in a total of 70 healthy premenopausal, perimenopausal, and postmenopausal women aged 40-58 years from February 2017 to October 2017. The bone marrow DW imaging signal characteristics were visually evaluated in comparison to the erector spinae muscle. Imaging data were acquired using a 1.5 T MRI yielding signal intensity values from a DWI-pulse sequence (b-value of 800 s/mm2; apparent diffusion coefficient (ADC) maps from b-values of 0-800 s/mm2), and a T2 mapping sequence covering the L2-L4 lumbar vertebrae. Serous estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured through venous blood assay. The relationship of the mean DW signal intensity (SIDWI) with T2 values, female hormone level, and mean ADC were analyzed using Spearman's rho test. RESULTS: The proportion of diffuse DWI hyperintensities of the bone marrow was significantly higher in premenopausal (91% (21/23)) women compared to peri- (75% (18/24)) and postmenopausal (8% (2/23)) women. A positive correlation was observed for the mean SIDWI (median [interquartile range], 47.33 [30.14]) and mean T2 (mean ± SD, 121.01 ± 13.54) (r = 0.438, p < 0.001) as well as for the mean SIDWI and E2 (median [interquartile range], 52.45 [92.78]) (r = 0.407, p < 0.001). A negative correlation was observed for the mean SIDWI and serous FSH (median [interquartile range], 15.55 [42.08]) as well as for the mean SIDWI and serous LH (median [interquartile range], 6.96 [31.06]) (r = -0.557, p < 0.001; r = -0.535, p < 0.001; respectively), but no significant correlation was found for mean SIDWI and mean ADC (mean ± SD, 599.36 ± 82.70) (r = 0.099, p = 0.415). A negative correlation was also encountered for the mean T2 values and serous FSH (r = -0.339, p = 0.004) as well as for the mean T2 values and serous LH (r = -0.281, p = 0.018). CONCLUSIONS: The mean SIDWI correlates positively with mean T2 and serous E2 values, while there's no significant correlation with mean ADC, indicating that T2 shine-through effects might interfere with bone marrow signaling on DW images. Knowledge of the bone marrow signal characteristics changing in DW images in close relationship with menstrual status is essential to correctly interpret DWI in clinical practice.

Mechanism of "aberrant liver regeneration" and its role in treatment of liver fibrosis / 药学学报

Liver fibrosis is a critical pathological structural basis of a variety of chronic liver diseases such as alcoholic liver disease, viral hepatitis and nodular cirrhosis, while liver regeneration is the key mechanism for protecting liver against multiple injuries, promoting inflammation resolution and reversing liver fibrosis. When fibrosis occurs after liver injuries, the alternation of liver regeneration status in fibrosis usually plays an essential role in the outcome of diverse liver diseases. In this review, the differences between "homeostatic regeneration", "normal regeneration" and "aberrant regeneration" were identified in terms of the occurrence conditions, the basic state of the liver, the effects on liver repair, the types of cells involved and the pathogenesis. Emphatically, we not only summarize the differences of mechanisms between "aberrant regeneration" and "normal regeneration" in the pathogenesis of liver fibrosis, but also elucidate the features of "aberrant regeneration" in various liver fibrosis models, as well as the therapeutic strategies for the treatment of liver fibrosis based on "aberrant regeneration", expecting to provide evidence and clues for considering the risks and proposing possible solutions in clinical treatment of liver fibrosis.

Nigrostriatal Dopamine Acting on Globus Pallidus Regulates Sleep.

Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (∼45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA afferents to the caudoputamen (CPu) using 6-hydroxydopamine and examined changes in sleep-wake profiles in rats. Rats with 80-90% loss of SNc neurons displayed a significant 33.7% increase in wakefulness (or sleep reduction). This increase significantly correlated with the extent of SNc DA neuron loss. Furthermore, these animals exhibited sleep-wake fragmentation and reduced diurnal variability of sleep. We then optogenetic-stimulated SNc DA terminals in the CPu and found that 20-Hz stimulation from 9 to 10 PM increased total sleep by 69% with high electroencephalograph (EEG) delta power. We finally directly optogenetic-stimulated GPe neurons and found that 20-Hz stimulation of the GPe from 9 to 10 PM increased total sleep by 66% and significantly increased EEG delta power. These findings elucidate a novel circuit for DA control of sleep and the mechanisms of abnormal sleep in BG disorders such as Parkinson's disease and Huntington's disease.

Present situation and development strategies of Chinese medicine preparation in medical institutions / 中国中药杂志

As the actual clinical reflecting of transform Chinese medicine special curative effect, Chinese medicine preparation not only satisfies the need of hospital clinic, scientific research and teaching, but also plays an important role in deepening medical and health system reform, improving people's health level and contributing to the economic growth. However, some problems about administration and approval (tending to western medicine), contraction of the scale, lack of synchronization for clinic and scientific research, and the imbalance of regional development make Chinese medicine preparation move forwards slowly in contradiction. It has not only reduced the effectiveness of the Chinese medicine preparation in hospital clinic, but also brought bad effect on modernized development of Chinese medicine preparation. Research shows that main influencing factors of status quo of Chinese medicine preparation in medical institution include imperfect laws and regulations, high cost than income, and shortage of talents in preparation research. The analysis indicated that the necessary measures to break the contradiction, improve clinical effect of Chinese medicine, and promote the modernization development of Chinese drugs preparation were as follows: government and related departments should strengthen the supporting force in policy by adjusting the examination and approval policy, speeding up dispensing use, reforming pricing system, including into medicare reimbursement, integrating advantage resources and so on; medical institution should actively carry out research and development of traditional Chinese Medicine through drawing the traditional and modern essence, reserving professional talents, and developing characteristic preparation; companies cooperate with hospitals for complementary advantages, which can rapidly transform Chinese medicine preparation into clinical practice.

Development of Chinese herbal pieces and analysis of problems of total quality management / 中国中药杂志

Chinese herbal pieces are a key factor to protecting the quality of the clinical efficacy of traditional Chinese medicine (TCM), and it is one of the basic elements of ensuring the quality of TCM and people's usage safety. However, Chinese herbal pieces has massive problem such as adulteration and counterfeit, dyeing and weighting, pesticide residues, heavy metals in excess of the standards, and all the issues are repeated excessive in the clinic treatment. These issues impacted sound development of production, management and use of TCM, but also brings common people hidden trouble for the clinical safety of medication. Protect and improve the quality of the Chinese herbal pieces demand that continue improve quality system, in-depth scientific research, and strengthen self-discipline and other factors. So it is fundamentally to ensure good quality of Chinese herbal pieces with the color, taste and shape by systematic supervision to it from the source, production, management and research, with strengthened implementation and en- forcement of the "3G".

Protective effects of early hypoxic post-conditioning in cultured cortical neurons.

PRIMARY OBJECTIVE: Recent evidence suggests that delayed hypoxic post-conditioning is neuroprotective. The aim of the present study was to test whether early post-conditioning applied immediately after hypoxia could protect cultured neurons from hypoxia/reoxygenation (H/R)-induced injuries. METHODS: Primary cortical neuronal culture depleted of microglia was exposed to H/R. Post-conditioning started immediately after hypoxia and consisted of three cycles of 15-minutes of reoxygenation and 15-minutes of hypoxia. Cell viability assay was performed using Cell Counting Kit-8 (CCK-8). Apoptosis was evaluated by Hoechst 33258 staining, FITC-Annexin V/PI double staining and Western blot assay (testing the cleaved caspase-3 expression). Reactive oxygen species (ROS), intracellular Ca(2+) and mitochondrial membrane potential (MMP) were examined using confocal laser-scanning microscopy. MAIN RESULTS: H/R significantly reduced cell viability and increased neuronal apoptosis and necrosis. Furthermore, the expression of cleaved caspase-3, ROS production and intracellular Ca(2+) were increased. MMP was attenuated. Injuries induced by H/R were substantially attenuated by early hypoxic post-conditioning. Changes in cleaved caspase-3 expression, ROS production, intracellular Ca(2+) level and MMP in response to H/R were significantly decreased by the post-conditioning. CONCLUSIONS: The findings demonstrated that early hypoxic post-conditioning could protect neurons against H/R-induced injuries independent of microglial cells, possibly by inhibiting ROS over-production and intracellular Ca(2+) accumulation and maintaining MMP.

Large-scale synthesis of flexible free-standing SERS substrates with high sensitivity: electrospun PVA nanofibers embedded with controlled alignment of silver nanoparticles.

A new and facile way to synthesize a free-standing and flexible surface-enhanced Raman scattering (SERS) substrate has been successfully developed, where high SERS-active Ag dimers or aligned aggregates are assembled within poly(vinyl alcohol) (PVA) nanofibers with chain-like arrays via electrospinning technique. The aggregation state of the obtained Ag nanoparticle dimers or larger, which are formed in a concentrated PVA solution, makes a significant contribution to the high sensitivity of SERS to 4-mercaptobenzoic acid (4-MBA) molecules with an enhancement factor (EF) of 10(9). The superiority of enhancement ability of this Ag/PVA nanofiber mat is also shown in the comparison to other substrates. Furthermore, the Ag/PVA nanofiber mat would keep a good reproducibility under a low concentration of 4-MBA molecule (10(-6) M) detection with the average RSD values of the major Raman peak less than 0.07. The temporal stability of the substrate has also been demonstrated. This disposable, easy handled, flexible free-standing substrate integrated the advantages including the superiority of high sensitivity, reproducibility, stability, large-scale, and low-cost production compared with other conventional SERS substrates, implying that it is a perfect choice for practical SERS detection application.