OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVE To investigate the relationship between azimuth direction,angular intervals,and the accuracy of azimuthal sound source localization.METHODS Fifteen young subjects with normal hearing were tested using nine azimuth settings.The test results were presented as root mean square error and percentage confusion.RESULTS The confusion rate under high-frequency narrowband noise was significantly higher than that under broadband noise and three-syllable words.In the frontal direction,statistically significant differences were observed between the 20° and 10° intervals,as well as between the 20° and 15° intervals(P<0.05),but no significant difference was found between the 10° and 15° intervals(P>0.05).In the lateral and rear directions,statistically significant differences were found between the 30° and 15° intervals,as well as between the 30° and 20° intervals(P<0.05),but no significant difference was found between the 15° and 20° intervals(P>0.05).Statistically significant differences were observed between the frontal direction and both the lateral and rear directions(P<0.05),but no significant difference was found between the lateral and rear directions(P>0.05).CONCLUSION Using stimuli that contain broader bandwidth cues can more accurately reflect the subject's horizontal localization ability.For source azimuth identification tests using broadband noise and three-syllable words,it is recommended to use a 15° interval in the frontal direction,and a 20° interval in the lateral and rear directions.The frontal and lateral directions can be preferred for testing.

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

Objective:The components of Rubus parvifolius L. were analyzed based on UPLC-MS/MS technology and combined with network pharmacology analysis to explore the mechanism of action of Rubi Parvifolii Radix in treating inflammation, cough, fever, influenza and sore throat. Method:The chemical constituents of Rubi Parvifolii Radix were identified according to the information of mass spectrometry. The network pharmacology was used to analyze the corresponding targets and related pathways of its chemical components, and the "component-target-pathway" interaction diagram was drawn. PyMOL 2.5.7 software wasused to perform molecular docking between active components and key targets.Results:Twenty chemical components were identified by UPLC-MS/MS, and 15 components were screened out by network pharmacology, which can be used as quality markers of Rubi Parvifolii Radix, namely Azelaic acid, Procyanidol B3, Caprolactam, Bis (2-ethylhexyl) adipate, Cryptochlorogenic acid, 3-O-Feruloylquinic, Ellagic acid, Aurantiamide acetate, 2 α,3 β,19 α,23-Tetrahydroxyurs-12-en-28-oic acid, L-Epicatechin, (E)-3-Indoleacrylic acid, Euscaphic acid, Suberic acid, Diisononyl phthalate and Prodelphinidin T4. Molecular docking showed that 5 compounds compared with the reference substance could bind to the target proteins of disease well. Conclusions:The 15 active ingredients in Rubi Parvifolii Radix, including Caprolactam and (E)-3-Indoleacrylic acid, may play a therapeutic role in treating colds, high fever, sore throat, and inflammation by acting on targets such as AKT1 and TNF. This provides a certain reference for the clinical application of Rubi Parvifolii Radix.

Objective:To establish a mass spectrometry method for the determination of characteristic peptides of Galli Gigerii Endothelium Corneum that can identify the authenticity of Galli Gigerii Endothelium Corneum as well as its preparations; To evaluate their quality.Methods:Ultra performance chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS) with the mode of multiple reaction monitoring quantification (MRM) was employed to monitor the ion pairs of m/z 379.21(charge: +2)→571.36, m/z 379.21(charge: +2)→385.26, m/z 785.41(charge: +2)→941.51 and m/z 785.41(charge: +2)→245.08, in order to detect the Galli Gigerii Endothelium Corneum crude drug and its preparations. Results:Chicken specific peptide I and chicken specific peptide Ⅱ could be detected in the 18 batches of Galli Gigerii Endothelium Corneum from different regions, their corresponding extractions and 4 batches of prescription preparations, while the chicken specific peptides were not detected in the 8 batches of endothelium corneums from ducks, geese and pigeons.Conclusions:The method established in this study can effectively supplement the deficiencies in standards of Galli Gigerii Endothelium Corneum and its decoction pieces, improve the quality control standard, and provide a reference for the safety and effectiveness of Galli Gigerii Endothelium Corneum in clinical medication.

Objective:To establish UPLC specific chromatogram method and content determination method of Dryopteridis Crassirhizomatis Rhizoma; To comprehensively evaluate the Dryopteridis Crassirhizomatis Rhizoma from different producing areas.Methods:UPLC method was used to establish the specific chromatogram of 15 batches of Dryopteridis Crassirhizomatis Rhizoma from different producing areas. The quality was evaluated by cluster analysis and partial least square analysis. The content of total flavonoids was determined by ultraviolet spectrophotometry.Results:The established specific chromatogram identified a total of 21 common peaks, and identified 4 components through comparison with control samples. The clustering and partial least squares analysis showed that the samples from Anshan City in Liaoning Province, Yanbian Korean Autonomous Prefecture in Jilin Province, Jiamusi City in Heilongjiang Province, Jilin City in Jilin Province had a certain consistency. The results of total flavone content determination showed that the content of samples from different producing areas was different.Conclusion:The established UPLC characteristic chromatogram and content determination method of total flavone content of Dryopteridis Crassirhizomatis Rhizoma can reflect the quality of Dryopteridis Crassirhizomatis Rhizoma in different places. The quality of samples from different origins is similar, but the contents of the three producing areas fluctuated greatly.

AIM:To examine how the variation of the β1-adrenergic receptor gene affects the occurrence of ventricular arrhythmias and the prognosis over a 6-month period in individuals suffering from acute ST-segment elevation myocardial infarction(STEMI).METHODS:A study was conducted retrospectively,where patients diagnosed STEMI and treated at Yunfu City People's Hospital between January 2021 and February 2023 were included based on predefined criteria.The patients were then divided into three groups according to their genotypes of the β1-adrenergic receptor Arg389Gly gene polymorphism:CC group(Arg389Arg),CG group(Arg389Gly),and GG group(Gly389Gly).Discrep-ancies in initial clinical data upon admission[such as Killip classification,heart rate,systolic and diastolic blood pres-sure,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVDD),and serum tumor necro-sis factor alpha(TNF-α),N-terminal pro-B-type natriuretic peptide(NT-proBNP),creatine kinase MB(CK-MB)and high-sensitivity C-reactive protein(hs-CRP)],and outcomes gathered during a 6-month follow-up via telephone after dis-charge(heart rate,NT-proBNP,CK-MB,LVEF,LVDD,and occurrences of major adverse cardiac events)were com-pared across the three groups.RESULTS:The study enrolled a total of 178 STEMI patients with ventricular arrhythmias,comprising 87 cases in CC group(48.9％),73 cases in CG group(41.0％),and 18 cases in GG group(10.1％).There were no notable variances in demographic characteristics such as age,sex,weight,BMI,smoking history,alcohol con-sumption history,comorbidities,blood pressure,heart rate,Killip classification(III amd IV),TNF-α,NT-proBNP,CK-MB,hs-CRP,LVEF and LVDD across the three groups(P>0.05).Following a 6-month monitoring period,the cardiac function parameters in CG and GG groups exhibited significant improvement compared to those in CC group(P<0.05),with noteworthy lower levels of NT-proBNP and CK-MB in GG group in contrast to CG group(P<0.05).Notably,there were significant discrepancies in the incidence of major adverse cardiac events during the follow-up period among the study groups,with 17 cases in CC group(19.5％),5 cases in CG group(6.9％),and 1 case in GG group(5.6％)(χ2=6.887,P<0.05).CONCLUSION:There is no correlation between the severity of STEMI accompanied by ventricular arrhyth-mias and the β1-adrenergic receptor Arg389Gly gene polymorphism.However,this gene variant is connected with en-hancements in cardiac function and short-term prognosis post-treatment.

This article introduces a high-magnification electronic endoscope system that utilizes a continuous zoom optical design,enabling high-magnification imaging at the cellular level.By selecting an appropriate initial retrofocus structure,the optimized modulation transfer function(MTF)curve of the zoom objective lens approaches the diffraction limit.Additionally,the tip and operation parts of the system incorporate modular gas-tight sealing and multiple layers of protective structure.The design employs efficient sealing materials and precise packaging techniques to ensure the system's sealing performance.The experimental results indicate that,under conventional imaging,the resolution is equivalent to 39.37 μm in object space,and the field of view angle is larger than 140 degrees.At magnified imaging,the resolution is equivalent to 2.78 μm in object space,and the observed actual field of view is greater than 800 μm×700 μm.When used with a 26-inch display monitor,the high-magnification electronic endoscope can achieve 500×optical magnification,allowing for the observation of features at the cellular level.Currently,this product has successfully achieved mass production and has undergone multiple animal trials,demonstrating its wide range of potential applications and significant clinical value.