1.Effect of Quercetin on Improving Myelin Sheath Injury and Neuropsychiatric Symptoms of VaD by Inhibiting Activation of Microglia in mPFC via RIPK1/NLRP3/Caspase-1 Pathway
Shiting LIANG ; Xinxian SHI ; Chen CHEN ; Xiaoxia FENG ; Jing QIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):126-134
ObjectiveTo investigate the ameliorative effects of quercetin on neuropsychiatric symptoms associated with vascular dementia (VaD) and to elucidate the molecular mechanism, specifically whether quercetin inhibits pro-inflammatory activation of microglia by modulation of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/NOD-like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway, thereby promoting myelin repair in the medial prefrontal cortex (mPFC). MethodsA C57BL/6J mouse model of VaD with neuropsychiatric symptoms was established by bilateral common carotid artery stenosis (BCAS) combined with chronic restraint stress (CRS). Mice were randomly divided into a sham group, a model group, low-dose, medium-dose, and high-dose quercetin groups (30, 60, 120 mg·kg-1·d-1), and a fluoxetine group (10 mg·kg-1·d-1). After intervention, depressive- and anxiety-like behaviors were assessed by the sucrose preference test (SPT), forced swim test (FST), open field test (OFT), and elevated plus maze (EPM). mPFC tissue was collected. Immunofluorescence (IF) was used to detect myelin basic protein (MBP) expression and microglial morphology. Western blot was used to measure the protein level of MBP, myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), inducible nitric oxide synthase (iNOS), CD86, RIPK1, phosphorylated RIPK1 (Ser166), NLRP3, and Caspase-1. Enzyme-linked immunosorbent assay (ELISA) was used to determine the level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). ResultsCompared with the sham group, the model group exhibited significant depressive- and anxiety-like behaviors (P<0.01), significantly decreased protein expression of MBP, MOG, and MAG in the mPFC (P<0.01), activated microglia (characterized by enlarged cell bodies, reduced protrusions, and upregulated iNOS and CD86 expressions, P<0.01), and significantly elevated p-RIPK1/RIPK1 ratio, NLRP3, Caspase-1 protein expression, and level of TNF-α, IL-6, and IL-1β (P<0.01, P<0.05). Compared with the model group, the quercetin treatment (especially at medium and high doses) significantly ameliorated these behavioral abnormalities (P<0.05, P<0.01), increased the expression of MBP (protein and fluorescence intensity), MOG, and MAG in the mPFC (P<0.05, P<0.01), suppressed excessive microglial activation (characterized decreased cell bodies, increased protrusions, and downregulated iNOS and CD86 expressions, P<0.01), and significantly reduced the p-RIPK1/RIPK1 ratio, NLRP3, Caspase-1 protein expression, and inflammatory cytokine levels (P<0.01). ConclusionQuercetin effectively alleviates neuropsychiatric symptoms in VaD mice. Its mechanism may be associated with the inhibition of microglial inflammatory activation mediated by the RIPK1/NLRP3/Caspase-1 signaling pathway, thereby promoting myelin repair in the mPFC region.
2.Effect of Huanglian Jiedutang in Improving Brain Iron Metabolism Disorders, Myelin Damage, and Aggressive Behavior in VaD Mice via Regulation of FBXL5/IRP2
Xiaoxia FENG ; Chen CHEN ; Jing QIU ; Guang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):1-9
ObjectiveThis study aims to investigate the effect of Huanglian Jiedutang on brain iron metabolism disorders, myelin damage, and aggressive behavior in vascular dementia (VaD) mice by regulating the F-box leucine-rich repeat protein 5 (FBXL5)/iron regulatory protein 2 (IRP2) pathway. MethodSixty C57BL/6J mice were randomly divided into six groups: sham operation group, model group, risperidone group (2 mg·kg-1·d-1), and low-dose, medium-dose, and high-dose groups of Huanglian Jiedutang (0.25, 0.5, 1 g·kg-1·d-1), with 10 mice in each group. The VaD model was established by bilateral carotid artery stenosis (BCAS). Drug intervention was administered for two weeks starting from the seventh week. Behavioral assessments, including the touch escape and resident-intruder tests, were conducted in the ninth week. After the behavioral tests, ventromedial hypothalamus ventrolateral (VMHvl) tissue samples were collected. Western blot was used to detect the expression of myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), 4-hydroxynonenal (4-HNE), glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), ferritin light chain (Ft-L), ferroportin 1 (FPN1), FBXL5, and IRP2. Immunofluorescence was used to measure MBP fluorescence intensity. Transmission electron microscopy was employed to observe ultrastructural changes in the myelin sheath. Perl's staining was used to detect tissue iron deposition. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by enzyme linked immunosorbent assay (ELISA). ResultCompared to the sham operation group, the model group exhibited a significant increase in biting, aggression, and irritability scores, along with a reduced latency of the attack (P<0.01). The expression levels of MAG, MOG, and MBP, as well as the fluorescent density of MBP, were significantly decreased (P<0.01). Disordered myelin ultrastructure, increased Ft-L and TFR1 expression, decreased FPN1 expression, and elevated iron deposition were observed (P<0.01). Antioxidants GPX4 and SOD were reduced, while 4-HNE and lipid peroxidation product MDA were increased (P<0.01). FBXL5 protein expression decreased, and IRP2 protein expression increased (P<0.01). Compared with the model group, in the middle-dose and high-dose groups of Huanglian Jiedutang and the risperidone group, the number of bites, aggressive behaviors, and irritability scores were reduced (P<0.05, P<0.01), while the latency of the attack increased (P<0.01). In the middle-dose and high-dose groups of Huanglian Jiedutang, the expression levels of MAG, MOG, and MBP, as well as MBP immunofluorescence increased (P<0.01). The ultrastructure was orderly arranged. Ft-L and TFR1 expression decreased; FPN1 expression increased, and iron deposition was reduced (P<0.01). GPX4 and SOD expression levels increased, and 4-HNE and MDA expression levels decreased (P<0.01). FBXL5 protein expression increased, and IRP2 protein expression decreased (P<0.01). ConclusionHuanglian Jiedutang may alleviate brain iron metabolism disorders, myelin damage, and aggressive behavior in VaD mice by regulating FBXL5/IRP2 expression in the VMHvl region.
3.Development and validation of a diagnostic model based on machine learning algorithms for the development of interstitial lung diseases in patients with rheumatoid arthritis
Yancong NIE ; Yanqing JIN ; Meilin YIN ; Xiaoxia WANG ; Lixia QIU
Chinese Journal of Rheumatology 2024;28(3):167-175
Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.
4.Real-time dynamic navigation assisted endodontic microsurgery:A case report
Yinchun ZHANG ; Xiaoxia YANG ; Xuan CHEN ; Lei HUANG ; Xiaoling QIU
Journal of Practical Stomatology 2024;40(5):720-722
With the demand for precise and efficient endodontic microsurgery,dynamic navigation technology has been reported for endo-dontic microsurgery in recent years,which is a digital navigation technology combining 3D reconstruction and spatial position alignment,pro-viding a new treatment model for minimally invasive endodontic microsurgery.In this paper,a case of endodontic microsurgery assisted by re-al-time dynamic navigation is reported.
5.Research progress on the effects of sodium-glucose linked transporter 2 inhibitors on multiple metabolic disorders in metabolic syndrome
Chunxiang XU ; Xiaoxia CAI ; Xingyu QIU ; Liang ZHAO
Journal of Zhejiang University. Medical sciences 2024;53(3):382-389
Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.
6.Study on the quality markers of Curcumae Radix standard decoction based on fingerprint and network pharmacology
Zhiwen DUAN ; Xiaoxia LIU ; Minyou HE ; Cuijie WEI ; Yongwei FENG ; Haibao QIU ; Ronghui ZHENG ; Dongmei SUN ; Xiangdong CHEN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(12):1622-1628
Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.
7.Clinical application of ultrasound combined with DSA-guided implantation of totally implantable venous access port via upper arm vein approach in chemotherapy for patients with malignant tumors
Guangxin JIN ; Fangqin ZHANG ; Yawen WANG ; Yan GUO ; Xiaoxia QIU ; Xuebin ZHANG
Journal of Interventional Radiology 2024;33(7):733-737
Objective To evaluate the technical feasibility and safety of upper arm vein approach in the implantation of totally implantable venous access port(TIVAP)under the guidance of ultrasound combined with DSA.Methods The clinical data of 1 546 patients with malignant tumors,who received TIVAP implantation via upper arm vein access under the guidance of ultrasound combined with DSA at the Affiliated Renji Hospital,School of Medicine of Shanghai Jiao Tong University of China between January 2020 and January 2022,were retrospectively analyzed.The implantation success rate,single-puncturing success rate,operation time,and complications were compared between the PICC catheterization room and the DSA operating room.Results The technical success rate in the 1546 patients was 100%,with a single-puncturing success rate of 99.48%.In 766 patients the TIVAP implantation was performed in the PICC catheterization room(PICC group),and in 780 patients the TIVAP implantation was carried out in the DSA operating room(DSA group).The mean operation time in the DSA group was(20.1±1.3)min,which was obviously shorter than(25.4±1.9)min in the PICC group,and the incidence of primary catheter misplacement in the DSA group was 0%,which was remarkably lower than 0.78%in the PICC group(P<0.05).No statistically significant differences in the incidences of complications,including infection,thrombosis,upper limb movement disorder,catheter occlusion,exposure of infusion port body,and overturn of infusion port body,existed between the two groups(P>0.05).Conclusion Ultrasound-guided TIVAP via upper arm vein approach is a safe and effective infusion route for patients with malignancy receiving chemotherapy.The combination use of ultrasound guidance and intraoperative DSA guidance can reduce the operation time as well as the incidence of operation-related complications.
8.Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies.
Zhenan DENG ; Meiling JIN ; Changxing OU ; Wei JIANG ; Jianping ZHAO ; Xiaoxia LIU ; Shenghua SUN ; Huaping TANG ; Bei HE ; Shaoxi CAI ; Ping CHEN ; Penghui WU ; Yujing LIU ; Jian KANG ; Yunhui ZHANG ; Mao HUANG ; Jinfu XU ; Kewu HUANG ; Qiang LI ; Xiangyan ZHANG ; Xiuhua FU ; Changzheng WANG ; Huahao SHEN ; Lei ZHU ; Guochao SHI ; Zhongmin QIU ; Zhongguang WEN ; Xiaoyang WEI ; Wei GU ; Chunhua WEI ; Guangfa WANG ; Ping CHEN ; Lixin XIE ; Jiangtao LIN ; Yuling TANG ; Zhihai HAN ; Kian Fan CHUNG ; Qingling ZHANG ; Nanshan ZHONG
Chinese Medical Journal 2023;136(2):230-232
9.Research status of screening and evaluation tools of post-extubation dysphagia in tracheal intubation patients
Jiaying TANG ; Yao LI ; Zhecan QIU ; Feiting ZHENG ; Xiaoxia HUANG
Chinese Journal of Modern Nursing 2023;29(10):1393-1396
Post-extubation dysphagia is a common problem in tracheal intubation patients. Timely identification of post-extubation dysphagia is helpful for clinical medical staff to adjust nursing strategies and improve patients' prognosis. This paper reviews the screening and evaluation tools of post-extubation dysphagia in tracheal intubation patients, so as to provide a reference for medical staff to identify post-extubation dysphagia patients in early stage.
10.Clinical factors influencing the effect of anti-reflux surgery for gastroesophageal reflux disease
Bin WANG ; Wei ZHANG ; Sheng LIU ; Xiaoxia CEN ; Ming QIU
Chinese Journal of General Surgery 2022;37(2):84-89
Objective:to analyze the risk factors for the side effect of anti-reflux surgery for gastroesophageal reflux disease (GERD) with regards to relief of reflux symptom, dysphagia and postoperative satisfaction.Method:The incidence of disappointing chief complaint among 192 patients who underwent anti-reflux surgery was analyzed. The related independent risk factors were identified by multivariate analysis.Results:The incidence of non-relief of reflux symptom was approximately 21.8% (42 cases), of which the risk factors were identified as preoperative depression and long-term PPI administration. The incidence of persistent dysphagia was 7.3% (14 cases), of which the risk factors were identified as preoperative depression and weak peristalsis of esophageal body. The incidence of postoperative dissatisfaction was 26.0% (50 cases), of which the risk factors were identified as long-term PPI administration and moderate-severe depression. The GERD patients with hiatal hernia and low pressure of lower esophageal sphincter were more likely benefit from anti-reflux surgery and had a higher postoperative satisfaction rate.Conclusion:Hiatal hernia and low pressure of lower esophageal sphincter are the favorable factors predicting good result of anti-reflux surgery. Long-term PPI administration and preoperative depression is an indication for poor result of anti-reflux surgery.

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