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.Establishment and validation of a risk prediction model for 90-day mortality in patients with acute-on-chronic liver failure based on sarcopenia
Huina CHEN ; Ming KONG ; Siqi ZHANG ; Manman XU ; Yu CHEN ; Zhongping DUAN
Journal of Clinical Hepatology 2025;41(6):1135-1142
ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure (ACLF) based on sarcopenia and other clinical indicators, and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital, Capital Medical University, from January 2019 to January 2022 were enrolled, and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group, CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra (L3), and L3 skeletal muscle index (L3-SMI) was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors, and a nomogram was developed for presentation. The area under the ROC curve (AUC) was used to assess the predictive performance of the model, the calibration curve was used to assess the degree of calibration, and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR]=1.962, 95% confidence interval [CI]: 1.185 — 3.250, P=0.009), total bilirubin (HR=1.003, 95%CI: 1.002 — 1.005, P<0.001), international normalized ratio (HR=1.997, 95%CI: 1.674 — 2.382, P<0.001), and lactic acid (HR=1.382, 95%CI: 1.170 — 1.632, P<0.001) were included in the sarcopenia-ACLF model. In the training cohort, the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF (0.80 vs 0.73, Z=1.97, P=0.049). In the test cohort, the sarcopenia-ACLF model had a significantly larger AUC than MELD score (0.79 vs 0.69, Z=2.70, P=0.007) and MELD-Na score (0.79 vs 0.68, Z=2.92, P=0.004). The calibration curve showed that the model had good calibration ability, with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities, the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients, which provides support for clinical decision-making and helps to optimize treatment strategies.
3.Interplay Between Interferon Stimulatory Pathways and Organellar Dynamics
Jin-Ru LI ; Yu DUAN ; Xin-Gui DAI ; Yong-Ming YAO
Progress in Biochemistry and Biophysics 2025;52(7):1708-1727
Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.
4.A case of repairing the destructive high-voltage electric burn wounds in the head, face, and neck based on the economic theory of flaps
Wanli GUO ; Peng DUAN ; Zhiguo MING ; Taiping WEI
Chinese Journal of Burns 2024;40(1):87-89
In September 8 th, 2021, a male patient (aged 18 years) with severe destructive injuries of high-voltage electric burns in the head, face, and neck was admitted to General Hospital of Taiyuan Iron Steel (Group) Co., Ltd. Based on the economic theory of flaps, the flap donor site and transplantation method were optimized and evaluated before surgery, and then debridement of head, face, and neck wounds+removal of necrotic skull+free transplantation of super large latissimus dorsi myocutaneous flap+thin intermediate thickness skin graft transplantation from the left thigh was performed. The extra large flap donor site wound was sutured directly. This surgery reduced the adverse consequences of the flap donor site on the premise of ensure of repair effect. After operation, the patient's condition was stable, the flap and skin graft survived well, the repair effect of wound was well, the scar in the flap donor area was relatively mild, and the upper limb had no dysfunction.
5.The structure,function and regulation mechanism of Vibrio fluvialis Type Ⅵ secretion system
Yu HAN ; Sai-Sen JI ; Qian CHENG ; Yuan-Ming HUANG ; Ran DUAN ; Wei-Li LIANG
Chinese Journal of Zoonoses 2024;40(6):571-577
Type Ⅵ secretion system(T6SS)is a lethal weapon that releases effectors in direct contact to kill eukaryotic predators or prokaryotic competitors.T6SS is of great significance in bacterial environmental adaptability,pathogenicity,and gene horizontal transfer.T6SS has been identified in about 25%of Gram-negative bacteria.Because of its widespread existence,T6SS is considered the key factor of ecological competition.T6SS effectors exerting biological functions have high diversity and do not have conserved sequences,and the regulatory mechanisms involved are complex.Therefore,it is a hot and difficult topic in T6SS research.Vibrio fluvialis(V.fluvialis)as a newly emerging foodborne pathogen,has unique characteristics in the quantity,composition,and physiological function of T6SS,which is related to its wide environmental adaptability and pathoge-nicity.This article mainly reviews the research progress of V.fluvialis T6SS,including its composition,structure,functional activity,and regulatory mechanism.
6.Quantitative diagnosis of early acute compartment syndrome using two-dimensional shear wave elastography in a rabbit model
Jun ZHANG ; Kunlong DUAN ; Junci WEI ; Wanfu ZHANG ; Huihui ZHOU ; Lin SANG ; Yuanyuan SUN ; Xue GONG ; Hao GUAN ; Ming YU
Ultrasonography 2024;43(5):345-353
Purpose:
This study explored the association of the elasticity modulus and shear wave velocity (SWV) of the tibialis anterior muscle, as measured by two-dimensional shear wave elastography (2D-SWE), with the intracompartmental pressure (ICP) determined using the Whitesides method in a New Zealand rabbit model of acute compartment syndrome (ACS). Additionally, it evaluated the viability of 2D-SWE as a noninvasive, quantitative tool for the early detection of ACS.
Methods:
An ACS model was established through direct external compression by applying pressure bandaging to the lower legs of 15 New Zealand rabbits using neonatal blood pressure cuffs. Another five animals represented a non-modeled control group. To measure the elasticity modulus and SWV of the tibialis anterior muscles, 2D-SWE was employed. Blood oxygen saturation, serum creatine kinase (CK), and myoglobin levels were monitored. Subsequently, the anterior tibial compartment was dissected, and the tibialis anterior was removed for hematoxylin and eosin staining to assess muscle injury.
Results:
The elasticity modulus and SWV of the tibialis anterior muscle increased with compression duration, as did serum CK and myoglobin levels. ICP was strongly positively correlated with these parameters, particularly mean velocity (r=0.942, P<0.001) and CK (r=0.942, P<0.001). Blood oxygen saturation was negatively correlated with ICP (r=-0.887, P<0.001). Histological analysis indicated progressive muscle cell swelling over time, with damage transitioning from reversible to irreversible and culminating in necrosis.
Conclusion
In a rabbit ACS model, ICP was strongly positively correlated with muscle elasticity modulus/SWV. Consequently, 2D-SWE may represent a novel tool for assessing early-phase ACS.
7.The current status and influencing factors of thriving at work among junior nurses
Siyu DUAN ; Ming HOU ; Min DING ; Yao SUN ; Ping LI
Chinese Journal of Nursing 2024;59(7):848-853
Objective To investigate the status of thriving at work among junior nurses,and to analyze the influencing factors,so as to provide theoretical bases for promoting the job growth of junior nurses and improving the level of thriving at work.Methods From January to March 2023,431 junior nurses from 3 tertiary hospitals in Xinjiang Uygur Autonomous Region were selected as the research subjects.Questionnaire survey were conducted through the General Information Questionnaire,the Thriving at Work Scale,and the Job Crafting Scale.The univariate analysis and multiple linear regression were used to analyze the influencing factors of thriving at work among junior nurses.Results A total of 431 nurses with low seniority completed the survey.The total score of thriving at work is(35.46±6.74)score.Multiple linear regression analysis showed that age,education level and job remodeling score were the factors affecting the job prosperity of junior nurses(P<0.05).Conclusion The thriving at work of junior nurses was at a moderate level.Nursing managers should strengthen the benign guidance of junior nurses,provide sufficient resource support,improve the level of job remodeling to promote the thriving at work of junior nurses and maintain the stability of organizational development.
8.Simultaneou determination of twenty-eight constituents in Dayuan Drink by UPLC-MS/MS
Yu-Jie HOU ; Xin-Jun ZHANG ; Ming SU ; Xin-Rui LI ; Yue-Cheng LIU ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Kang-Ning XIAO ; Long-Yun DUAN ; Lei CAO ; Zhen-Yu XUAN ; Shan-Xin LIU
Chinese Traditional Patent Medicine 2024;46(11):3545-3552
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.
9.Clinical effects of Xuanfei Jiejing Decoction combined with conventional treatment on patients with asthma of Wind-Phlegm Obstructing Lung Pattern
Yun GUAN ; Lei WU ; Xuan ZHANG ; Ming-Ming DUAN ; Fei-Fei PENG
Chinese Traditional Patent Medicine 2024;46(11):3636-3640
AIM To investigate the clinical effects of Xuanfei Jiejing Decoction combined with conventional treatment on patients with asthma of Wind-Phlegm Obstructing Lung Pattern.METHODS One hundred and fifty patients were randomly assigned into control group(75 cases)for 4-week intervention of conventional treatment,and observation group(75 cases)for 4-week intervention of both Xuanfei Jieshi Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,airway inflammatory indices(ECP,IL-4,IgE),lung function indices(FVC,FEV1/FVC,PEF)and putum and mucus indices(4 h sputum volume,sputum viscosity,mucin 5AC)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,airway inflammatory indices,putum and mucus indices(P<0.05),and increased lung function indices(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with asthma of Wind-Phlegm Obstructing Lung Pattern,Xuanfei Jiejing Decoction combined with conventional treatment can reduce airway inflammatory levels,inhibit airway mucus secretion,improve lung functions,and alleviate clinical symptoms.
10.Application progress of artificial intelligence in cardiovascular health management
Kun WANG ; Ming LI ; Xiao-Bo ZHANG ; Yi-Ping XIA ; Pei-Wei ZHAO ; Ying-Zhong DUAN
Chinese Medical Equipment Journal 2024;45(2):92-96
The current situation of artificial intelligence(AI)was introduced when applied in the key links of cardiovascular health management such as risk prediction,early screening,clinical decision support and health consultation and education.The deficiencies of AI during the application were analyzed,and the prospects and development directions of AI in cardiovascular health management were pointed out.[Chinese Medical Equipment Journal,2024,45(2):92-96]

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