1.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.
2.Comparative efficacy of vNOTES and LESS in the management of benign uterine lesions in obese patients
Wenyuan LI ; Min WEI ; Jie HAN ; Ruifeng LI ; Zhen WANG ; Hailan LI ; Jing XU ; Dongmei JIN ; Lingyan XU ; Rong PENG ; Yan ZHANG ; Xinhua SUN
The Journal of Practical Medicine 2024;40(22):3184-3189
Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.
3.Mechanism of malignant behavior in cervical cancer cells based on NOD2-mediated AMPK/mTOR signaling pathway
Ruiting DU ; Dongyue WU ; Qingmin GUO ; Dongmei JIN
Acta Universitatis Medicinalis Anhui 2024;59(2):316-324
Objective To explore the mechanism of malignant behavior of cervical cancer(CC)cells based on AMP-activated protein kinase(AMPK)/rapamycin target protein(mTOR)signaling pathway mediated by nucleo-tide-binding oligomerization domain receptor 2(NOD2).Methods Bioinformatics analysis was performed to deter-mine the expression of NOD2 in CC tissue.Plasmids targeting NOD2(shNOD2)and shRNAs negative control(shNC),NOD2 overexpression(NOD2)and vectors(Vec)were transfected into CC cells.The effect of NOD2 on the growth of CC cells was determined by cell counting kit-8 assay,colony formation and Transwell cell invasion as-say.Transcriptome analysis was performed by high throughput RNA sequencing(RNA-Seq).Western blot was used to detect the expression of NOD2,AMPK/mTOR signaling pathway and autophagy protein in the cell line.24 female BALB/c nude mice were randomly divided into four groups,with 6 mice in each group:vector group(Vec group),NOD2 overexpression group(NOD2 group),shNC group and shNOD2 group.The distant metastasis mod-el was established in mice,and the fluorescence intensity of lung metastasis was monitored and the number of lung metastasis nodules was counted.Results On-line database analysis showed that the expression of NOD2 in CC tis-sues was significantly higher than that in normal tissues,and there were significant differences in the mRNA expres-sion of NOD2 in different stages of CC(P<0.05).In addition,the high expression of NOD2 was associated with poor overall survival and disease-free survival(P<0.05).NOD2 overexpression promoted the proliferation,colony formation,migration and invasion of CC cells,while NOD2 knock-down was the opposite.Consistent with the re-sults in vitro,the lung colonization and lung metastasis of CC cells in NOD2 group were significantly higher than those in Vec group(P<0.05),while those in shNOD2 group were significantly lower than those in shNC group(P<0.05).RNA-Seq results showed that the expression of NOD2 was significantly related to AMPK signal activa-tion,mTOR signal inhibition,autophagy regulation pathway activation and autophagy formation.Compared with shNC group,the expression of phosphorylated AMPK and LC3 protein decreased significantly in shNOD2 group(P<0.05),and the expression levels of phosphorylated mTOR and p62 protein increased significantly(P<0.05).Compared with Vec group,the expression levels of LC3 and AMPK protein in NOD2 group increased significantly(P<0.05),and the expression levels of phosphorylated mTOR and p62 protein decreased significantly(P<0.05).Compared with shNC group,the point accumulation of GFP-mRFP-LC3 in shNOD2 group decreased signifi-cantly(P<0.05).Compared with Vec group,the point accumulation of GFP-mRFP-LC3 increased significantly(P<0.05).Conclusion NOD2 may promote the proliferation,migration and invasion of CC through AMPK/mTOR signal,and its mechanism partly involves autophagy activation.
4.Assessment of different bone marrow infiltration patterns with MR whole-body diffusion weighted imaging in multiple myeloma
Yawen WU ; Dongmei WANG ; Hongwei CAO ; Fengzhen CUI ; Chengyuan XU ; Jie LIU ; Chengyu JIN ; Boyi LI ; Yuqing LI
Journal of Practical Radiology 2024;40(6):952-956
Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P>0.99),and there was statistically significant difference in ADC values between the other groups(P<0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95%confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95%CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.
5.Development and validation of a questionnaire regarding knowledge, attitude and practice of the ICU nurses′ family-centered sensory stimulation
Dongmei TANG ; Li ZENG ; Hong ZHANG ; Weiling TAO ; Jin HAN
Chinese Journal of Practical Nursing 2023;39(19):1456-1462
Objective:To establish a questionnaire regarding knowledge, attitude and practice on family-centered sensory stimulation among ICU nurses and examine its reliability and validity, so as to provide basis for subsequent nursing training targeted sensory stimulation.Methods:Based on the theory of knowledge, attitude and practice, the questionnaire of family-centered sensory stimulation for ICU nurses was constructed by literature review, semi-structured interview, expert consultation and questionnaire survey. From March to April 2022, convenience sampling was used to investigate 253 ICU nurses from 8 general hospitals in four provinces and cities to test the reliability and validity of the questionnaire.Results:The final questionnaire included 33 items in 3 dimensions, and the cumulative variance contribution rate was 76.248%. The average content validity index of the total questionnaire was 0.970, and the content validity index of each item ranged from 0.894 to 1.000. The Cronbach′s α coefficient of the questionnaire was 0.965, the split-half reliability was 0.799, and the retest reliability was 0.818 after 2 weeks.Conclusions:It has good validity and reliability in this questionnaire and can be used as a preliminary assessment tool to understand the status quo of family-centered sensory stimulation in ICU nurses.
6.Analysis on the recovery time and influencing factors of deglutition disorders after extubation in neurosurgery patients
Jin HAN ; Li ZENG ; Rongqing LI ; Yawen WU ; Dongmei TANG ; Sailu MAO
Chinese Journal of Practical Nursing 2023;39(26):2013-2019
Objective:To investigate the occurrence of deglutition disorders after extubation in neurosurgery patients, to explore the recovery time and influencing factors, and to provide reference for the development of nursing intervention plan for dysphagia after extubation.Methods:This was a prospective study. A total of 250 patients who underwent oral catheterization under general anesthesia in neurosurgery department and were admitted to the Tenth People′s Hospital of Tongji University from June to December 2022 were selected as the study objects by convenience sampling method. The general demographic and clinical data of the patients were collected to evaluate the occurrence of deglutition disorders after extubation. The outcome and recovery time of deglutition disorders were used as dependent variables. Kaplan-Meier method and Cox proportional hazard regression analysis were used to analyze the recovery time and influencing factors of deglutition disorders after extubation in neurosurgery patients.Results:The incidence of deglutition disorders after extubation was 35.6%(89/250) among 250 cases of neurosurgery patients under general anesthesia by endotracheal intubation, the recovery time of Deglutition Disorders after postoperative extubation was 1 - 16 (5.17 ± 0.43)days. ICU stay days, duration of endotracheal intubation and the first standardized swallowing assessment after extubation were the main influencing factors for the recovery of deglutition disorders in patients with dysphagia after extubation.Conclusions:For patients with deglutition disorders after extubation after neurosurgery, ICU stay days, duration of endotracheal intubation and the first standardized swallowing assessment after extubation affect the process of swallowing function recovery. Medical staff should focus on the risk groups and develop targeted nursing interventions to improve the outcome of patients.
7.Etiological diagnosis value of metagenomic next generation sequencing in the patients with spinal infection
Dongmei ZHANG ; Weili ZHAN ; Huiming JIN ; Zhen PENG ; Shuai DING ; Dongqiang YANG ; Yanhong KANG ; Yuehua KANG ; Jia SHANG ; Erhui XIAO
Chinese Journal of Infectious Diseases 2023;41(3):208-213
Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.
8.Mechanism of Hirudo in Treatment of Stroke: A Review
Hanying XU ; Dongmei ZHANG ; Jing LU ; Yabin CUI ; Lei WU ; Zhuming CHEN ; Ziqi JIN ; Zhiguo LYU ; Peng XU ; Yibin ZHANG ; Tianye LAN ; Jian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):209-217
Stroke is one of the most common cerebrovascular diseases, including hemorrhagic stroke and ischemic stroke. From a modern medical perspective, stroke is caused by cerebrovascular damage or embolism leading to impaired blood circulation. From the traditional Chinese medicine (TCM) perspective, the pathogenesis of this disease is mainly due to the disorder of Qi and blood, which ascend to the brain, causing either blood extravasation or blockage of brain collaterals. Stasis is a pathological factor that runs throughout the entire course of stroke, and the method of promoting blood circulation and resolving stasis has been a core treatment for stroke for a long time. Hirudo, as a traditional insect drug, has shown good effects in promoting blood circulation and resolving stasis. Modern pharmacological research has confirmed that Hirudo contains anticoagulant components, which provide significant advantages in dissolving thrombi in ischemic stroke and facilitating hematoma absorption in hemorrhagic stroke. Hirudo and its related preparations have been proven to exert an anti-stroke effect through anticoagulation, anti-thrombosis, and protection of vascular endothelium. As a result, they have been widely used in the treatment of stroke. This article explored the theoretical basis and research status of using Hirudo for treating stroke based on its main active components and hemostatic properties and summarized the current research status of commonly used Hirudo-based formulations and preparations, aiming to provide references for the involvement of Hirudo in stroke treatment.
9.Establish a training program for caregivers of dementia patients in nursing homes based on the Model of Caregiver Skill Building/Effectiveness
Zihan LIN ; Jin LI ; Qian ZHAO ; Dongmei SI ; Jing WANG
Modern Clinical Nursing 2023;22(10):58-64
Objective To establish a training program for caregivers of people with dementia based on the Model of Caregiver Skill Building/Effectiveness and evaluate its practical effect.Methods The objective sampling method was used to select 72 caregivers from two nursing homes which were the specialised shelters for the dementia elderly in Xi'an.The subjects were randomly divided into a training group with 39 caregivers and a control group with 33 caregivers.The control group received training in routine care,while the training group was given training based on Farran's Model of Caregiver Skill Building/Effectiveness for 3 months.The training was composed of our modules:caring knowledge,skills,emotion management and resource utilisation,which included key training elements in knowledge of dementia and nursing,emotion management through yoga and mental training and improvement of nursing skills through instructions.The caregiver burden inventory(CBI)and self-rating depression(SDS)were used to evaluate the effect of caregivers training before and after the training.Result After the training,the scores CBI and SDS of the caregivers were significantly lower than those in the control group and lower than the scores before training(all P<0.05).Conclusion The training program based on the Model of Caregiver Skill Building/Effectiveness can effectively reduce the burden and depression of caregivers in dementia care.
10.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

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