1.Effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease model rats
Yu LEI ; Jing LU ; Wenjuan HE ; Jiaying GU ; Dengfeng ZHOU
China Pharmacy 2025;36(8):939-944
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.
2.Optineurin restrains CCR7 degradation to guide type II collagen-stimulated dendritic cell migration in rheumatoid arthritis.
Wenxiang HONG ; Hongbo MA ; Zhaoxu YANG ; Jiaying WANG ; Bowen PENG ; Longling WANG ; Yiwen DU ; Lijun YANG ; Lijiang ZHANG ; Zhibin LI ; Han HUANG ; Difeng ZHU ; Bo YANG ; Qiaojun HE ; Jiajia WANG ; Qinjie WENG
Acta Pharmaceutica Sinica B 2025;15(3):1626-1642
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.
3.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
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.
4.Development and Clinical Application of High-Magnification Electronic Endoscope
Fan WANG ; Jiansong XIA ; Hui YANG ; Guofei YAN ; Jiaying HE ; Liqiang WANG
Chinese Journal of Medical Instrumentation 2024;48(6):658-663
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.
5.Impact of β1-adrenergic receptor gene polymorphism on ventricular ar-rhythmias and short-term prognosis in STEMI patients
Jiaying CHEN ; Liwei HE ; Yingqu ZHUANG
Chinese Journal of Pathophysiology 2024;40(9):1645-1651
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.
6.Study on the quality of the Dryopteridis Crassirhizomatis Rhizoma from different producing areas
Siqiong CAO ; Yunjing QIU ; Jiaying HE ; Chunlin ZHONG ; Min XU
International Journal of Traditional Chinese Medicine 2024;46(9):1187-1192
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.
7.Comparison of horizontal plane auditory spatial discrimination abilities and testing methods in patients with symmetrical sensorineural hearing loss
Lai WEI ; Jiaying LI ; Xing WANG ; Xiaolin HE ; Shuai NIE ; Xin FU ; Huan LI ; Jiaxing LIU ; Xuelei ZHAO ; Zihui ZHAO ; Ningyu WANG ; Juan ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(9):922-927
Objective:To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration.Methods:A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson′s correlation to assess the relationship between MAA and degree of hearing loss.Results:MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss ( r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration ( F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions:The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.
8.An Intelligent Method for Optimizing Large-volume Medical Image Transmission.
Jiaying HU ; Yi WANG ; Ping HE
Chinese Journal of Medical Instrumentation 2023;47(1):61-65
In order to alleviate the conflict between medical supply and demand, and to improve the efficiency of medical image transmission, this study proposes an intelligent method for large-volume medical image transmission. This method extracts and generates keyword pairs by analyzing medical diagnostic reports, and uses a 3D-UNet to segment original image data into various sub-area based on its anatomy structure. Then, the sub-areas are scored through keyword pairs and preset scoring criteria, and transmitted to user frontend in the order of prioritization score. Experiments show that this method can fulfill physicians' requirements of radiology reading and diagnosis with only ten percent of data transmitted, which efficiently optimized traditional transmission procedures.
9.Behavioral guidance for non-medical volunteers in designated isolation facilities
Yue ZHAO ; Jiansheng LIN ; Ming HU ; Junyan FAN ; Jiaying SHEN ; Hongsen CHEN ; Ruihua WANG ; Yida HE ; Xiaoqiong ZHU ; Guangwen CAO
Shanghai Journal of Preventive Medicine 2022;34(9):922-929
Corona virus disease 2019 (COVID-19) has led to more than 500 million cases, including 6.19 million deaths. Mutated strains of SARS-CoV-2 (alpha, beta, gamma, delta and omicron) have successively emerged. Currently the omicron variant is gradually replacing the delta variant, driving a surge of cases in most countries including China, posing a great challenge to the prevention and treatment of COVID-19. In the face of the severe pandemic situation, a large number of non-medical volunteers are fighting on the front lines of the war against the pandemic and are vulnerable to exposure due to lack of professional knowledge. This paper introduces the routine skills training of volunteers and emergency response, aiming to provide behavioral guidance for non-medical volunteers in designated isolation facilities.
10.Experience in nursing management of negative pressure isolation ward for suspected COVID-19 patients
Jing LI ; Jiaying SONG ; Xiufang LI ; Chensi GAO ; Ying ZHANG ; Lili HE
Chinese Journal of Experimental and Clinical Virology 2021;35(6):732-734
With the outbreak of COVID-19 in the world, Beijing is one of the main areas of the imported cases. As a designated hospital for treatment in Beijing, our hospital set up a negative pressure isolation ward for suspected COVID-19 patients in an emergency, and we quickly organized nursing training, implemented classified management of hospitalized patients. During the whole process of setting up the new ward, all the related staff started working quickly, the logistics department provided goods timely, and the isolation facilities were set tightly. Owing to those, we completed the task of receiving and treating the suspected COVID-19 cases.

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