Objective:The variability of the apnea-hypopnea index（AHI） measured in the first and second halves of the night is significant in patients with obstructive sleep apnea hypopnea syndrome（OSAHS）. This variation may be related to fluid redistribution caused by the supine position during sleep. Methods:Eighty-nine adult subjects were enrolled. Circumferences（neck, chest, waist, and calf） were measured before sleep onset and upon awakening. Polysomnography（PSG） was performed, and the night was divided into two halves based on the midpoint of total sleep time to calculate AHI for each half. The correlation between changes in AHI and changes in circumferences was analyzed. Results:Twenty simple snorers and sixty-nine OSAHS patients were included, with a median AHI of 22.6（11.8, 47.3） events/hour. Compared to pre-sleep measurements, there was no significant change in neck circumference upon awakening in the control group（P=0.073）, while reductions were observed in the other three measurements（P=0.006, P=0.038, P<0.001）. In the OSAHS group, neck circumference increased（P<0.001）, and reductions were noted in the other three measurements（P<0.001 for all）, with the most significant change observed in calf circumference 40.0（37.1, 42.0） cm to 38.0（35.8, 40.5） cm. Compared to the first half of the night, total AHI, supine AHI, and NREM AHI significantly decreased in the second half（P=0.010, P=0.031, P=0.001）, while no significant changes were observed in lateral AHI and REM AHI（P=0.988, P=0.530）. Further analysis revealed a significant relationship between increased chest circumference and decreases in NREM AHI, supine AHI, and supine NREM AHI（P=0.036, P=0.072, P=0.034）, as well as between decreased lateral position AHI and increased waist circumference（P=0.048）. Additionally, this study found a negative correlation between changes in calf circumference and changes in AHI（R=-0.24, P=0.048）, while neck circumference changes positively correlated with changes in AHI（R=0.26, P=0.03）. Conclusion:In OSAHS patients during the second half of sleep compared to before sleeping, chest circumference, waist circumference, and calf circumference decrease while neck circumference increases; total AHI, supine position AHI, and NREM period AHI decrease; increases in chest circumference are associated with decreases in NREM period AHI, supine position AHI, supine position NREM period AHI. There is nocturnal variability in AHI among OSAHS patients that may be associated with fluid shifts during sleep.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Polysomnography ; Fluid Shifts/physiology* ; Adult ; Middle Aged ; Neck ; Severity of Illness Index ; Sleep/physiology* ; Snoring/physiopathology*

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To investigate the effect of β-elemene on mitochondrial structure and function of the A549 cells of non-small cell lung cancer(NSCLC),and to elucidate the mechanism of β-elemene in the treatment of NSCLC.Methods:The A549 cells at logarithmic growth stage were divided into blank control group(0 mng·L-1 β-elemene),low,medium and high doses of β-elemene groups(10,25 and 50 mg·L-1),and solvent control group(0.5％ethanol in equal volume).After treatment for 24 h,the cell activities in various groups were detected by MTT assay;the morphology changes of mitochondria in the cells in various groups was observed by transmission electron microscope;the levels of adenosine 5′-triphosphate(ATP)in the cells in various groups were detected by colorimetry;the mitochondrial membrane potential of the A549 cells in various groups were detected by JC-1 flow cytometry;mitochondrial membrane permeability transfer hole assay was used to detect the mitochondrial membrane permeabilities of the cells in various groups.Results:The MTT results showed that compared with blank control group,the cell activities in low,medium and high doses of β-elemene groups were decreased gradually(P＜0.05),while the cell activity in solvent control group had no significant change,and the difference was not significant(P＞0.05).The transmission electron microscope results showed that compared with blank control group,the mitochondria of A549 cells in low,medium and high doses ofβ-elemene groups showed swelling,vacuolation,disordered arrangement and dissolution,while the mitochondrial morphology of the A549 cells in solvent control group had no significant changes.The colorimetric method results showed that compared with blank control group,the ATP levels in the A549 cells in low,medium and high dose β-elemene groups were gradually decreased(P＜0.05),while the ATP level in the A549 cells in solvent control group had no significant change,and the difference was not significant(P＞0.05).The JC-1 flow cytometry method results showed that compared with blank control group,the mitochondrial membrane potential of the A549 cells in low,medium and high doses ofβ-elemene groups were decreased,and the percentages of the cells in Q2-4 region were increased(P＜0.05);the percentage of the A549 cells in the Q2-4 region in solvent control group had no significant change.The results of mitochondrial membrane permeability transfer hole experiment showed that compared with blank control group,the mitochondrial membrane permeabilities of the A549 cells in low,medium and high doses of β-elemene groups were increased,and the percentages of the cells in M4 region were increased(P＜0.05);the mitochondrial membrane permeability of the A549 cells and the percentage of the M4 cells in solvent control group had no significant changes,and the difference was not significant(P＞0.05).Conclusion:β-elemene can inhibit the proliferation of the A549 cells,and the mechanism may be that the mitochondrial structure of A549 cells is damaged by reducing the level of ATP and mitochondrial membrane potential,changing the mitochondrial morphology and increasing the mitochondrial membrane permeability.

Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

Objective:To observe the clinical effect of arthrocentesis combined with liquid phase con-centrated growth factor(CGF)injection in the treatment of unilateral temporomandibular joint osteoarthri-tis(TMJOA),in order to provide a new treatment option for TMJOA patients.Methods:In this non-randomized controlled study,patients diagnosed with unilateral TMJOA who visited the center for tem-poromandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects.The patients were divided into experi-mental group and control group,which were selected by patients themselves.The experimental group re-ceived arthrocentesis combined with liquid phase CGF injection and the control group received arthrocen-tesis combined with HA injection.Both groups were treated 3 times,once every two weeks.The clinical effect was evaluated by the maximum mouth opening,pain value and the degree of mandibular function limitation 6 months after treatment.The change of condylar bone was evaluated by cone beam CT(CBCT)image fusion technology before and after treatment.Results:A total of 20 patients were included in the experimental group,including 3 males and 17 females,with an average age of(34.40± 8.41)years.A total of 15 patients were included in the control group,including 1 male and 14 females,with an average age of(32.20±12.00)years.There was no statistical difference in general information between the two groups(P＞0.05).There were no statistical differences in the mouth opening,pain value and the degree of jaw function limitation between the two groups before treatment(P＞0.05),and all of them improved 6 months after treatment compared with before treatment(P＜0.05).However,the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment(P＜0.05),and the degree of jaw function limitation was significantly lower than that of con-trol group(P＜0.05).CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment,and image fusion results showed that 10 patients(50.0％)in the experimental group and 5 patients(33.3％)in the control group had reparative remodeling area of con-dylar bone,and there was no statistical difference between them(P＞0.05).Except for one CGF pa-tient,the other patients in both groups had some absorption areas of condylar bone.Conclusion:The ar-throcentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term,and is better than HA in increasing mouth opening and impro-ving jaw function.CBCT fusion images of both patient groups show some cases of condylar bone repara-tive remodeling and its relevance to treatment plans still requires further study.

Objective:To evaluate the role of Ras homolog gene family member A (RhoA) in hydrogen-induced alleviation of lipopolysaccharide (LPS)-caused damage to pulmonary microvascular endothelial cell(PMVEC) barrier function in mice.Methods:PMVECs were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% penicillin/streptomycin until 4-6 passage. These cells were divided into 6 groups ( n=36 each) using a random number table method: control group (group A), hydrogen-rich medium group (group B), LPS group (group C), LPS + hydrogen-rich medium group (group D), LPS + RhoA inhibitor C3 enzyme group (group E) and LPS + hydrogen-rich medium + RhoA agonist U-46619 group (group F). Cells were cultured within normal medium in group A, group C and group E and within hydrogen-rich medium in group B, group D and group F. LPS at a final concentration of 1 μg/ml was simultaneously added in group C, group D, group E and group F. C3 enzyme at a final concentration of 3 μg/ml was added at 2 h before addition of LPS in group E. U-46619 at a final concentration of 10 mg/ml was added at 3 h before addition of LPS in group F. The expression of vascular endothelial (VE)-cadherin and occludin was determined by Western blot at 6, 12 and 24 h after incubation with LPS. At 24 h after incubation with LPS, the release rate of LDH was measured by LDH method, cell viability was measured by MTT method, and the activity of RhoA was determined by GST pull-down method. Results:Compared with group A, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group C ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group D ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group E ( P<0.05). Compared with group D, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group F ( P<0.05). Conclusions:RhoA is involved in hydrogen-induced alleviation of LPS-caused damage to PMVEC barrier function in mice.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To investigate the dynamic changes and molecular mechanisms of myocardial injury and autophagy as the body's self-protective mechanism at different time points after cerebral ischemia/reperfusion(CI/R).Methods A CI/R model was established in male Sprague-Dawley rats using the Longa thread method.Rats that underwent CI/R following middle cerebral artery occlusion were classified into 6-,12-,24,and 48-hour groups according to the reperfusion time.The concentrations of reactive oxygen species and reac-tive nitrogen species were measured to evaluate myocardial oxidative stress.Cardiomyocyte apoptosis and autophagosomes were observed in the myocardium.Additionally,dynamic changes in myocardial autophagy,autophagic flux,and protein and gene expression of auto-phagy regulators were detected.Results Oxidative-stress-induced injury and apoptosis were observed in the myocardium after CI/R.The number of autophagosomes in cardiomyocytes increased,peaking in the 12 h group,and autophagic flux was impaired during the first 12 h after CI/R.Beclin 1,mammalian target of rapamycin(mTOR),and adenosine monophosphate-activated protein kinase(AMPK)expression levels in the myocardium increased during the first 48 h after CI/R,peaking in the 12 h group.This was consistent with changes in autophagy,which showed significant differences compared with the control group.Conclusion These results indicated that autophagy plays a protective role against CI/R-induced myocardial injury.Furthermore,Beclin 1-mediated autophagy/apoptosis and mTOR-mediated autophagy mutual feedback pathways play important roles in the regulation of autophagy.

Objective To comprehensively analyze the epidemiological characteristics and resistance mechanisms of New Delhi metallo-β-lactamase(NDM)-positive multidrug-resistant bacteria in China.Methods Relevant literatures on NDM-positive multidrug-resistant bacteria discovered in China were searched in the CNKI and PubMed databases(publications from January 1,2017 to December 31,2023).The epidemiological analysis was conducted on the types of NDM-positive bacterial strains,their regional distribution,infection sources,resistance profiles,and transfer mechanisms.Results A total of 118 eligible articles were collected,reporting 1627 NDM-positive bacterial strains.The number of reports increased annually from 2011 to 2019,but began to decline annually from 2020 onwards.NDM-1 and NDM-5 were the most commonly reported variants.The highest number of reports came from Eastern China,followed by Central China and North China.The primary pathogens were Klebsiella pneumoniae,Escherichia coli,and Enterobacter cloacae.The age distribution of patients with NDM-positive infections showed distinct patterns,with neonates and children accounting for 27.25％and patients over 50 years old accounting for 49.57％.The majority of positive bacterial infections came from sputum(38.28％),urine(28.94％),and blood(23.28％).The main departments reporting NDM-positive bacteria were the ICU(39.93％)and pediatrics(20.14％).These resistant bacteria exhibited resistance to more than 50.00％of antibiotics,with lower resistance to colistin and tigecycline(below 30.00％).The predominant plasmid type carrying the blaNDMwas IncX3,and the insertion sequences upstream and downstream of the blaNDM showed diversity.Conclusion NDM-positive multidrug-resistant bacteria are widely prevalent across regions in China,exhibiting multidrug-resistance.This poses significant challenges to clinical antibiotic selection and necessitates the development of effective countermeasures.