1.Screening of Antidepressant Active Components from Curcumae Rhizoma and Its Mechanism in Regulating Nrf2/GPX4/GSH Pathway
Yonggui SONG ; Delin DUAN ; Meixizi LAI ; Yali LIU ; Zhifu AI ; Genhua ZHU ; Huanhua XU ; Qin ZHENG ; Ming YANG ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):211-221
ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
2.Mechanism of action of energy metabolism in hepatic ischemia-reperfusion injury and related targeted therapies
Tiantian YANG ; Lu HUANG ; Xiao ZHANG ; Yali REN ; Weitian XU ; Song ZHANG
Journal of Clinical Hepatology 2025;41(9):1956-1960
Hepatic ischemia-reperfusion injury (HIRI) is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy, and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies, in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.
3.Expert consensus on clinical protocol for treating herpes zoster with fire needling.
Xiaodong WU ; Bin LI ; Baoyan LIU ; Lin HE ; Zhishun LIU ; Shixi HUANG ; Keyi HUI ; Hongxia LIU ; Yuxia CAO ; Shuxin WANG ; Zhe XU ; Cang ZHANG ; Jingsheng ZHAO ; Yali LIU ; Nanqi ZHAO ; Nan DING ; Jing HU
Chinese Acupuncture & Moxibustion 2025;45(12):1825-1832
The expert consensus on the clinical treatment of herpes zoster with fire needling was developed, and the commonly used fire needling treatment scheme verified by clinical research was selected to form a standardized diagnosis and treatment scheme for acute herpes zoster and postherpetic neuralgia (PHN), so as to answer the core problems in clinical application. The consensus focuses on patients with herpes zoster, and forms recommendations for 9 key clinical issues, covering simple fire needling and TCM comprehensive therapy based on fire needling, including fire needling combined with cupping, fire needling combined with Chinese herb, fire needling combined with cupping and Chinese herb, fire needling combined with filiform needling, fire needling combined with moxibustion, and provides specific recommendations and operational guidelines for various therapies.
Humans
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Herpes Zoster/therapy*
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Acupuncture Therapy/instrumentation*
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Consensus
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Clinical Protocols
4.Hyssopus cuspidatus extract inhibited OVA-sensitized allergic asthma through PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.
Yali ZHANG ; Huiming PENG ; Jingjing LI ; Pan LV ; Mengru ZHANG ; Xu WANG ; Siyu WANG ; Siying ZHU ; Jiankang LU ; Xuepeng FAN ; Jinbo FANG
Chinese Herbal Medicines 2025;17(3):539-547
OBJECTIVE:
To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma.
METHODS:
Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation.
RESULTS:
Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine.
CONCLUSION
HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.
5.Clinical and genetic analysis of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy
Liuyu SUN ; Huijie XIAO ; Yali REN ; Ke XU ; Xuhui ZHONG ; Hongwen ZHANG ; Yuegui ZENG ; Fang WANG
Chinese Journal of Medical Genetics 2024;41(10):1231-1237
Objective:To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy. Methods:A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by Medical Ethics Committee of the Peking University First Hospital (Ethics No. 2016[1029]).Results:The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c. 737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+ PM2_Supporting+ PM3+ PP3+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b. Conclusion:The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.
6.Feasibility study on integrated imaging of portal vein and hepatic vein with"three low-contrast agents"combined with energy spectrum CT technology
Jingjing WU ; Lunqing PU ; Guihua LI ; Zhengyang GAO ; Taisong TANG ; Junhong BI ; Yali PENG ; Xi YANG ; Haoran XU
Journal of Practical Radiology 2024;40(7):1175-1178
Objective To explore the feasibility of integrated imaging of portal vein and hepatic vein with"three low-contrast agents"combined with energy spectrum CT technology.Methods A total of 100 patients with enhanced abdominal CT scans were selected.The patients were randomly divided into two groups.The patients of experimental group(n=50)were injected with the isotonic con-trast agent iodixanol(320 mg I/mL)at a flow rate of 3 mL/s and a total volume of 1.2 mL/kg,and underwent energy spectrum CT scan in the portal venous phase.The patients of control group(n=50)were injected with the sub-hypertonic contrast agent iohexol(350 mg I/mL)at a flow rate of 5 mL/s and a total volume of 1.5 mL/kg,and underwent conventional multi-phase spiral CT enhancement scan.The image quality and radiation dose of portal vein and hepatic vein were compared between the two groups.Results The CT value of main portal vein in the experimental group was higher than that in the control group,and the difference was statistically sig-nificant(P<0.05).There was no statistical significance in main portal vein contrast-to-noise ratio(CNR),main portal vein signal-to-noise ratio(SNR),hepatic vein CT value,and hepatic vein CNR between the two groups(P>0.05).The SNR and image standard deviation(SD)of the hepatic vein in the control group were better than those in the experimental group(P<0.05).There was no statistical significance in the subjective scores of portal vein and hepatic vein between the two groups(P>0.05).The volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)of the portal venous phase spectrum CT scan in the experimental group were lower than those of the conventional single-phase spiral CT scan in the control group(P<0.05).Conclusion"Three low-contrast agents"combined with energy spectrum CT technology can realize integrated imaging of portal vein and hepatic vein in late portal vein,and can reduce radiation dose.
7.Evaluation of Crohn's disease treatment efficacy with CT enterography
Fang WEN ; Fuxia XIAO ; Kun PENG ; Yali XU ; Guangyu TANG ; Yi FEI
Journal of Practical Radiology 2024;40(8):1300-1303
Objective To explore the value of CT enterography(CTE)in the clinical treatment efficacy evaluation of Crohn's disease(CD).Methods A total of 55 patients with CD confirmed by clinical and pathology were selected.All patients both underwent CTE and enteroscopy before and after treatment.After treatment,the patients were divided into the good curative effect group and the poor curative effect group according to Crohn's disease activity index(CDAI).The CT findings were both analyzed before and after treatment.Results There were significant differences in bowel wall thickness,bowel wall attenuation,bowel wall thickness type and"comb sign"of 55 CD patients before and after treatment(P<0.05).After treatment,phlegmon,abscess,swollen lymph node enlargement,and intestinal fistula all decreased from 18%,7%,27%,and 2%to 2%,2%,9%,and 0%,respectively.Also,there were significant differences in bowel wall thickness,bowel wall attenuation,bowel wall thickness type and"comb sign"between the good curative effect group and the poor curative effect group(P<0.05).Logistic regression analysis and receiver operating characteristic(ROC)curve analysis showed bowel wall thickness,bowel wall attenuation and bowel wall thickness type were the most valuable parameters for the treatment efficacy evaluation of CD patients.Conclusion CTE can fully show intestinal lesions and extrenteral complications,and is of great value in evaluating clinical treatment efficacy of patients.
8.Issues in primary care of anaphylaxis in children
Lei XI ; Yali YANG ; Qiuyu YAO ; Xu LU
Chinese Pediatric Emergency Medicine 2024;31(7):497-500
In recent years, there has been an increasing trend regarding the incidence of anaphylaxis among children in China. Despite the existence of relevant diagnosis and treatment guidelines for regulation, due to reasons such as uneven allocation of medical resources, there are still many problems in the specific implementation process of primary health care institutions, and these problems may lead to untimely and irregular handling of allergic reactions, thereby increasing the risk for pediatric patients. This review discussed the related issues existing about the diagnosis and treatment of anaphylaxis in children in primary health care institutions.
9.Risk factors and predictive models for liver cancer after sustained virologic response in hepatitis C
Shanshan XU ; Lixia QIU ; Yali LIU ; Jing ZHANG
Journal of Clinical Hepatology 2024;40(6):1259-1263
Hepatitis C is one of the main causes of liver cancer.With the application of direct-acting antiviral agents,more than 95%of patients can achieve the eradication of hepatitis C virus and obtain sustained virologic response(SVR).Effective antiviral therapy can change the natural course of hepatitis C and reduce the risk of liver cancer;however,some patients are still affected by age,sex,liver fibrosis,diabetes,hepatic steatosis,alcohol consumption,and genetic factors and become the high-risk population of liver cancer.Therefore,it is needed to further clarify and improve the identification and prediction of high-risk populations of liver cancer after SVR of hepatitis C.This article reviews the risk factors and predictive models for liver cancer after SVR in patients with hepatitis C,in order to provide a basis for identifying the high-risk population of liver cancer after SVR of hepatitis C in clinical practice.
10.Construction and validation of Alignment Diagram model for risk of parenteral nutrition-associated cholestasis in extremely/ultra-low birth weight infants
Shuyan CHEN ; Jinglin XU ; Yali CAI ; Yunting HU ; Qingling ZHU ; Zhiyong LIU ; He WANG ; Jingyang ZHENG ; Dongmei CHEN
Chinese Pediatric Emergency Medicine 2024;31(2):114-119
Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis(PNAC)in extremely/ultra-low birth weight infants,and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020,using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software,and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included,with a median gestational age of 29.14(28.00,30.86)weeks and a median birth weight of 1 170(1 000,1 300)g.Among them,26(12.81%)cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition( OR=1.015 ,95% CI 1.003-1.034),the cumulative amount of glucose( OR=1.014 ,95% CI 1.001-1.028),small for gestational age( OR=3.455 ,95% CI 1.127-10.589),and neonatal sepsis( OR=3.142 ,95% CI 1.039-9.503)were independent risk factors for PNAC( P<0.05);The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model,the area under the receiver operating characteristic curve was 0.835(95% CI 0.842-0.731),and the results of the Hosmer Limeshow goodness of fit test show that:χ 2=5.34,degree of freedom=8, P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate,with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition,glucose accumulation,small for gestational age infants,and neonatal sepsis exhibits high predictive ability,and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

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