1.Molecular Mechanism Mediated by HIF-1α/HO-1 Signaling Pathway of Guizhi Fulingwan in Suppressing Ferroptosis in Endometriosis
Li TANG ; Yi ZHANG ; Lulu WU ; Yingying LIANG ; Wenying GONG ; Quanning TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):1-11
ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan (GFW) inhibits ferroptosis in endometriosis (EMT) through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 (HIF-1α/HO-1) signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT, including core targets. Functional enrichment analysis was conducted to explore the biological processes, molecular functions, cellular components, and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated, model, positive control (dienogest at 0.2 mg·kg-1), low-dose GFW (2.5 g·kg-1), and high-dose GFW (5 g·kg-1). After modeling, the rats received their respective treatment by oral gavage for 28 consecutive days, while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin (HE) staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot were conducted to assess mRNA and protein expression of HIF-1α, HO-1, glutathione peroxidase 4 (GPX4), spermidine/spermine N1-acetyltransferase (SAT1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Tissue levels of malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe²⁺) were quantified using commercial assay kits. Serum levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were measured via enzyme-linked immunosorbent assay (ELISA). ResultsFive ferroptosis-related biomarkers in EMT were identified: ALOX12, CHAC1, SAT1, AST1, and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment, with FOS, JUN, HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group, the model group exhibited significant increases in both mRNA and protein expression of HIF-1α, HO-1, and PTGS2, as well as elevated tissue levels of Fe²⁺ and MDA. Conversely, GSH levels and the expression of GPX4 and SAT1 were markedly reduced, and serum levels of IL-6 and TGF-β1 levels were significantly higher (P<0.01). Compared with the model group, all GFW-treated groups showed significant downregulation of HIF-1α and HO-1, reduced Fe²⁺ levels, and downregulated expression of MDA, PTGS2, IL-6, and TGF-β1. Meanwhile, GSH, GPX4, and SAT1 expression levels were significantly increased (P<0.05, P<0.01), effectively ameliorating iron overload and oxidative stress, thereby demonstrating therapeutic efficacy in EMT, with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation, providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.
2.Target prediction and preliminary validation of quercetin in treatment of endometriosis
Yi ZHANG ; Lulu WU ; Li TANG ; Jiao CUI ; Wanjing YUAN ; Wenying GONG ; Jiao ZHU ; Xiuwei LYU
Journal of Army Medical University 2025;47(16):1913-1922
Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.
3.Clinical characteristics of patients with puerperal schizophrenia
Xiaohua LU ; Haijing LI ; Qijie KUANG ; Wenying YI ; Yu XIA ; Nyunan ZHOU ; Yingjun ZHENG ; Shenglin SHE
Sichuan Mental Health 2024;37(1):52-56
BackgroundWomen may develop severe symptoms of stress disorder following childbirth, which may be exposed to a risk of developing mental health problems, and even lead to the recurrence of the illness in female patients with schizophrenia, while comparatively limited research has been undertaken concerning the clinical characteristics and treatment of puerperal schizophrenia in China. ObjectiveTo explore the clinical characteristics of puerperal schizophrenia, so as to provide references for the clinical treatment. MethodsA total of 24 patients with puerperal schizophrenia who were hospitalized in the female ward of adult psychiatry department of the Affiliated Brain Hospital of Guangzhou Medical University from 2012 to 2020 and met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for schizophrenia were included as puerperal group. Another 48 non-puerperal women with schizophrenia were concurrently enrolled as control group. Then the basic data, scores on Positive and Negative Symptom Scale (PANSS) and the discharge medication were recorded. ResultsThe percentages of newly onset and positive family history of psychosis in puerperal group were larger than those in control group, with statistical significance (χ2=9.321, 5.240, P<0.05 or 0.01). Puerperal group scored higher on PANSS excitement factor (t=-2.220, P<0.05) and lower on negative factor (t=3.377, P<0.01) compared with control group. In terms of discharge medication, puerperal group reported a higher dosage of antipsychotic drugs (t=-2.095, P<0.05), and a larger proportion of combined use of benzodiazepines or antidepressants (χ²=21.316, 5.114, P<0.05 or 0.01) compared with control group, with statistical significance. ConclusionPatients with puerperal schizophrenia display increased ratings of excitement symptoms and decreased ratings of negative symptoms, which necessitates the use of high doses of antipsychotic drugs, and combined use of benzodiazepines and antidepressants.
4.Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency
Jing SUN ; Shuai ZHANG ; Wenying KANG ; Yi CHANG ; Dong ZHAO ; Hongwei GUO ; Xiangyang QIAN ; Zhe ZHENG
Chinese Journal of Surgery 2024;62(5):393-399
Objective:To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency.Methods:This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups.Results:Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was ( M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group ( P<0.01). Conclusions:Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.
5.Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency
Jing SUN ; Shuai ZHANG ; Wenying KANG ; Yi CHANG ; Dong ZHAO ; Hongwei GUO ; Xiangyang QIAN ; Zhe ZHENG
Chinese Journal of Surgery 2024;62(5):393-399
Objective:To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency.Methods:This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups.Results:Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was ( M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group ( P<0.01). Conclusions:Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.
6.The practice of clinical pharmacists participating in the management of prophylactic antibiotics during the perioperative period of thoracic surgery
Yi LIU ; Jiarong CHEN ; Wenying HONG
Chinese Journal of Primary Medicine and Pharmacy 2023;30(3):393-398
Objective:To explore the role of clinical pharmacists participating in the management of prophylactic antibiotics during the perioperative period of thoracic surgery, and to evaluate the effects after participating in the practice.Methods:The use of antimicrobials during the perioperative period of thoracic surgery in Wenjiang Hospital of Sichuan Provincial People's Hospital in August 2019 (pre-practice) was retrospectively analyzed. The existing problems were summarized, and the possible causes of the existing problems were analyzed. The improvement measures were jointly developed by clinical pharmacists and physicians. Clinical pharmacists continued to manage the use of antimicrobials by means of medication order reviews, ward rounds for pharmacy service, and medication training. The use of prophylactic antibiotics during the perioperative period of thoracic surgery was compared between August 2019 (pre-practice group) and December 2019 (post-practice group) and the practical effect was evaluated.Results:Clinical pharmacists reviewed perioperative patients' medication orders once a day, ward rounds for pharmacy service twice a week, and medication training once a month. Twenty-two patients were enrolled before practice, and 26 patients were enrolled after practice. There were no significant differences in age, sex, body weight, operative time, type of surgical incision, and preventive use of antibiotics between the two groups (all P > 0.05). In the post-practice group, the appropriate time for preoperative administration was 100.0%, which was significantly higher than 88.2% in the pre-practice group. The reasonable rate of preoperative preventive drug selection was 100.0%, which was significantly higher than 44.4% in the pre-practice group ( χ2 = 17.50, P < 0.001). In the post-practice group, the duration of preventive medication was (1.82 ± 0.59) days, which was significantly shorter than (7.54 ± 3.25) days in the pre-practice group ( t = 11.97, P < 0.001). In the post-practice group, the cost of antibacterial drugs was 316.00(237.00,454.25) yuan, which was significantly lower than 1 136.00(391.81 , 2 184.65) yuan in the pre-practice group ( Z = -2.78, P < 0.05). The defined daily dose of antibiotics among inpatients was 2.67(2.00,3.42), which was significantly lower than 8.88(3.92 , 19.18) in the pre-practice group ( Z = -3.26, P < 0.05). There were no significant differences in the incidence of postoperative pulmonary infection and total length of hospital stay between the two groups (both P > 0.05). Conclusion:Clinical pharmacists participating in the management practice of perioperative prophylactic antibiotics in thoracic surgery can effectively promote the rational application of perioperative antibiotics, markedly improve the reasonable rate of prophylactic drug delivery, shorten the course of prophylactic drugs, reduce the cost of antibiotics, decrease the defined daily dose of antibiotics, without increasing the risk of postoperative pulmonary infection and the total length of hospital stay.
7.Construction of the evaluation index system for standardized training of newly recruited nurses
Yanan LI ; Wenying WANG ; Yi CAO ; Shuoguo HUANG ; Xiaobing DU ; Chuanhong LIU ; Xiaoping LOU
Chinese Journal of Modern Nursing 2021;27(13):1802-1807
Objective:To construct a systematic, standardized, scientific and effective evaluation index system for standardized training of newly recruited nurses.Methods:By the literature review, applying the Delphi method and purpose sampling to conduct two rounds of expert consultations to 17 nursing experts from 5 medical units and 1 nursing school from October 2019 to April 2020 to construct the evaluation index system for standardized training of newly recruited nurses.Results:The recovery rates of the two rounds of expert consultation questionnaires were all 100%, and the expert authority coefficient was 0.92. The final evaluation index system for standardized training of newly recruited nurses included 4 first-level indicators (professional literacy, theoretical knowledge, nursing operation skills, and core competency of the post) , 17 second-level indicators, and 52 third-level indicators.Conclusions:The evaluation index system for standardized training of newly recruited nurses established in this study is systematic, scientific and effective, which can provide a reference for standardized training and evaluation of newly recruited nurses, and provide a theoretical basis and practical guidance for improving the training effect and quality.
8.Interpretation of subjective cognitive decline characteristics published in Lancet Neurology
Yu SUN ; Xiaoni WANG ; Guanqun CHEN ; Can SHENG ; Xuanyu LI ; Qin YANG ; Taoran LI ; Wenying DU ; Xiaoqi WANG ; Li LIN ; Yi LIU ; Feng FENG ; Xiaochen HU ; Ying HAN
Chinese Journal of Neurology 2020;53(5):396-400
Alzheimer′s disease (AD) is an incurable disease in the field of major chronic diseases. Subjective cognitive decline (SCD) is a clinical risk factor for AD. The standardized screening and intervention in individuals with SCD are of great importance in early prevention and treatment of AD. According to the clinical criteria proposed by The characterisation of subjective cognitive decline, which was published online in Lancet Neurology, the article summarized the definition of SCD, the latest perspective of clinical standards in SCD, and the results of AD preclinical SCD research. The purpose of this work was to provide concrete guidance and recommendations for making clinical decisions in diagnosis and scientific research on SCD.
9.Restless legs syndrome in ischemic stroke patients: clinical features and significance.
Lisan ZHANG ; Yi SUN ; Tiantian WANG ; Yu PAN ; Ying YAO ; Liuqing PAN ; Qinglin XU ; Wenying ZHANG ; Jiahui XU ; Xingyue HU
Journal of Zhejiang University. Medical sciences 2019;48(3):275-281
OBJECTIVE:
To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients.
METHODS:
A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls.
RESULTS:
Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (=-133.3 mg/L, 95%:-200.4--0.1, <0.01), subcortical infarction (=4.05, 95%:1.15-14.18, <0.05) and female (=2.54, 95%:1.04-6.23, <0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%:2.33-6.41, <0.01), PHQ-9 increased by 2.17 (95%:0.39--3.94, <0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%:-1.79--0.15, <0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (=4.27, 95%:1.40-13.10, <0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (=12.85, 95%:2.04-23.67, <0.05).
CONCLUSIONS
RLS is common in ischemic stroke patients and has adverse influences on patients.
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pathology
10.Inhibitory and dispersive effects of betaine on formation of Staphylococcus aureus biofilm
Fei JIN ; Yi WEN ; Yuqiao XU ; Yaning MEI ; Wenying XIA ; Jue WANG ; Fang NI
Chinese Journal of Clinical Laboratory Science 2017;35(4):261-263
Objective To observe the formation of Staphylococcus aureus biofilm and the inhibitory and dispersive effects of betaine on the biofilm.Methods The inhibitory and dispersive effects of 0.1% betaine on the biofilm from 20 strains of Staphylococcus aureus were examined by crystal violet assay.Results All the 20 strains of Staphylococcus aureus formed biofilm.The biofilm of methicillinsensitive Staphylococcus aureus (MSSA) was formed in 24 hours with peak value of absorbance (A590 nm) (1.99 ± 0.53).The biofilm of methicillin-resistant Staphylococcus atureus(MRSA) was formed in 48 hours with peak value of absorbance(A590 nm) (1.13 ±0.47).After adding betaine,the absorbance(A590 nm) of MSSA biofilm fell down to(1.74 ± 0.61) in 24 hours,while the absorbance(A590 nm) of MRSA biofilm fell down to(0.40 ± 0.12) in 48 hours,which was significantly reduced compared with the controls (t =2.43,5.84,P < 0.05 respectively).When adding betaine after the biofilm formed,the absorbancies (A590 nm) of both MSSA and MRSA showed no significant difference compared with the controls (P > 0.05).Conclusion Betaine could inhibit biofilm formation of Staphylococcus aureus at concentration of 0.1%,but it could not disperse the mature biofilm of Staphylococcus aureus.

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