1.Comparing the Anti-oxidative Effects of "Three Decoctions for COVID-19"
Ximeng LI ; Yuan KANG ; Yuan GAO ; Zhuangzhuang LIU ; Wenjing LI ; Zhenlu XU ; Xiaoyu ZHANG ; Runlan CAI ; Yun QI
Chinese Journal of Modern Applied Pharmacy 2024;41(7):887-894
OBJECTIVE
To compare the anti-oxidative effects of "three decoctions for COVID-19" (Qingfei Paidu decoction, Huashi Baidu decoction, Xuanfei Baidu decoction) in parallel experimental models.
METHODS
In the cell-free system, the total antioxidant capacity was investigated by FRAP method. The scavenging effects of DPPH radicals and superoxide anions were evaluated by DPPH and NBT reduction method, respectively. The scavenging effect of hydroxyl radicals was determined by a fluorescence method based on the end-product MDA. The anti-lipid peroxidation activity was investigated using the FeSO4-induced rat liver homogenate MDA method. Based on these five antioxidant indicators, the antioxidant capabilities of the extracts of three decoctions were parallelly compared in the cell-free system. Furthermore, in lipopolysaccharide-activated RAW264.7 cells, the productions of intracellular and mitochondrial reactive oxygen species(ROS) were detected using the L-012 probe and the MitoSOX mitochondrial superoxide red fluorescence probe, respectively; and intracellular NADPH oxidase activity was measured using the lucigenin probe. These three indicators were used to parallelly compare the antioxidant capabilities of the extracts of three decoctions.
RESULTS
In the cell-free system, three decoctions for COVID-19 could concentration-dependently scavenge DPPH radicals, superoxide anions and hydroxyl radicals, and potently inhibit the lipid peroxidation. At the equal extract concentration, their scavenging effects on DPPH radicals and superoxide anions and the total antioxidant capacity were comparable; while Huashi Baidu decoction exhibited the strongest ability to scavenge hydroxyl radicals and inhibit lipid peroxidation. In the cell system, three decoctions could reduce lipopolysaccharide-elevated intracellular ROS level by weakening NADPH oxidase activity; meanwhile, they could decrease mitochondrial ROS productions, among which Qingfei Paidu decoction possessed the most comprehensive effection.
CONCLUSION
Collectively, three decoctions for COVID-19 exert diverse antioxidant effects in both cell-free and cell systems, and each of them possesses the distinct advantages. Given that oxidative stress is pivotal during the pathological process of COVID-19, the results may suggest that the antioxidant ability of three decoctions is one of the pharmacodynamic basis for their clinical use.
2.The mechanism of Bufei Tongbi Decoction in treatment of systemic lupus erythematosus interstitial lung disease based on network pharmacology and verification of key regulation pathway
Shangwen WU ; Huan LI ; Xiaohong GONG ; Chaoqun LU ; Yiming CHEN ; Ximeng LI ; Yan LI ; Songwei LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1256-1271
Objective To explore the effect and possible pharmacological mechanism of Bufei Tongbi Decoction in the treatment of systemic lupus erythematosus interstitial lung disease (SLE-ILD).Methods The effective components and related targets of Bufei Tongbi Decoction were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Uniprot database. Key genes for SLE-ILD were screened based on DrugBank,DisGeNET,GeneCards,PharmGKB,OMIM,and GEO databases. Using Cytoscape software,a drug active ingredient-target-disease relationship network diagram was constructed to obtain the effective active ingredients and possible mechanisms of action of Bufei Tongbi Decoction in the treatment of SLE-ILD. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal related target genes and pathway functions. Taking C57BL/6 mice as normal group,MRL/lpr mice were injected with bleomycin 5mg/kg in the nasal cavity. According to the random number table method,the mice were divided into model group,Bufei Tongbi Decoction low-dose group (10.4 g/(kg·d)),Bufei Tongbi Decoction medium-dose group (20.8 g/(kg·d)),Bufei Tongbi Decoction high-dose group (41.6 g/(kg·d)) and prednisone group (3 mg/(kg·d)). The intervention lasted for 28 days. Hematein eosin and Masson staining were used to observe the pathological changes of mouse lung tissue,the expressions of transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Col-Ⅲ) in lung tissue were detected by immunohistochemistry,and the expressions of interleukin-1β(IL-1β),interleukin-10 (IL-10) and interleukin-17 (IL-17) in serum were detected by ELISA. The mRNA expressions of matrix metallopeptidase 1(MMP-1),hypoxia inducible factor-1α(HIF-1α),retinoid-related orphan receptor γt (RORγt ) and forkhead box P3 (FOXP3) in lung tissue were analyzed by RT-PCR,the protein expressions of HIF-1α and MMP-1 in lung tissue were detected by Western blotting,and the expressions of T helper 17 cells (Th17) and regulatory T cells (Treg cells) in blood were detected by cytometry.Results A total of 163 effective ingredients,259 targets,1729 SLE-ILD disease targets,958 SLE-ILD differential genes and 40 drug-disease interaction targets were obtained by screening. GO functional enrichment and KEGG pathway enrichment showed that IL-17 signaling pathway activated by IL-1β and MMP-1,and Th17 cell differentiation activated by IL-1β and HIF-1α were the main pathways. Animal experiments showed that Bufei Tongbi Decoction could effectively improve the degree of lung interstitial lesion and reduce the expressions of TGF-β1 and Col-Ⅲ in SLE-ILD mice (P<0.01). The expressions of IL-1β,HIF-1α and IL-17 were decreased (P<0.01). Medium and high doses of Bufei Tongbi Decoction decreased the expressions of MMP-1 and RORγt mRNA (P<0.01),and increased the expressions of IL-10 and FOXP3 mRNA (P<0.01). Bufei Tongbi Decoction could reduce the proportion of Th17 cells,increase the proportion of Treg cells,downregulate the balance of Th17/Treg (P<0.05),and improve the immune disorder. Conclusion Bufei Tongbi Decoction has the characteristics of multi-target and multi-pathway in treating SLE-ILD,and its mechanism may be related to the regulation of Th17/Treg cell balance.
3.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.
4.Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor
Jia QI ; Zhou YINYIN ; Song LI ; Shi XIMENG ; Jiang XUAN ; Tao RUIZHI ; Wang AIYUN ; Wu YUANYUAN ; Wei ZHONGHONG ; Zhang YINAN ; Li XIAOMAN ; Lu YIN
Journal of Pharmaceutical Analysis 2024;14(7):1047-1062
Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.
5.Clinical Efficacy of Compound Tripterygium wilfordii Preparation(Xinfeng Capsules) in Improving Immune Inflammation of Rheumatoid Arthritis Due to Spleen Deficiency and Dampness Exuberance Based on Apriori Algorithm and Random Walk Model
Ziheng ZHU ; Lei WAN ; Jian LIU ; Chuanbing HUANG ; Lei ZHAO ; Yanyan FANG ; Shu LI ; Ximeng MA ; Fangze LI ; Saisai HU ; Yingying CHEN ; Jing CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):32-38
ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis (RA) due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method, with 51 cases in each group. All patients were treated with methotrexate tablets, while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score (DAS28), visual analogue scale (VAS) scores, morning stiffness time, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, vascular endothelial growth factor (VEGF), and serum amyloid A (SAA) of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP, ESR, RF, SAA, VEGF, and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment, the total effective rate in the observation group was 90.19% (46/51), which was higher than 74.51% (38/51) in the control group (χ2=4.320,P<0.05). DAS28, VAS score, and morning stiffness time in the observation group were improved compared with those in the control group (P<0.05). Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF, ESR, hs-CRP, SAA, and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP, ESR, RF, SAA, and VEGF in the observation group were all better than those of the control group, and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP, ESR, RF, SAA, and VEGF in the observation group was superior to that of the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than in the control group (χ2=4.057,P<0.05). ConclusionOn the basis of the treatment with methotrexate tablets, Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.
6.Correlation between collateral circulation and cerebral hemodynamics in moyamoya disease and moyamoya syndrome based on 4-dimensional CT angiography-CT perfusion
Yao LU ; Ling LI ; Ruoyao CAO ; Yi HE ; Yanhua WANG ; Ximeng YANG ; Huijing LIU ; Juan CHEN
Chinese Journal of Radiology 2023;57(3):252-258
Objective:To explore the significance of four-dimensional CT angiography(4D CTA) and CT perfusion (CTP) imaging in evaluating collateral circulation grades in patients with moyamoya disease and moyamoya syndrome and their relationship with cerebral hemodynamics.Methods:The clinical and imaging data of 32 patients with moyamoya disease and moyamoya syndrome in Beijing Hospital from January 2017 to January 2022 were retrospectively analyzed. All patients underwent 4D CTA-CTP imaging. Collateral circulation was scored on CTA images by using Alberta stroke program early CT score system, and on digital subtraction angiography (DSA) images by using American society of interventional and therapeutic neuroradiology/Society of interventional radiology score system, respectively. The patients were divided into Ⅰ-Ⅲ circulation compensation grades based on collateral circulation score. Regions of interest were delineated at basal ganglia on perfusion maps and the perfusion parameters were obtained including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), mean transit time (TTP) and delay time (DLY). The Kruskal-Wallis test was used to compare the perfusion parameters in different collateral circulation grades, and pairwise comparison was performed with Bonferroni correction. Kappa and Spearman tests were used to analyze the consistency and correlation of 4D CTA and DSA in the classification of collateral circulation.Results:4D CTA and DSA had a moderate consistency (Kappa=0.693, P<0.001) and a strong correlation ( r=0.805, P<0.001) in evaluating collateral grades. There were statistically significant differences in CBF, MTT and TTP among collateral compensation grade Ⅰ, grade Ⅱ and grade Ⅲ ( H values were 7.91, 11.69, 8.93; P values were 0.019, 0.003 and 0.012, respectively). Further pairwise comparison showed that the CBF of collateral compensation grade Ⅰ was lower than that of grade Ⅲ ( P=0.015), MTT of grade Ⅱ was higher than that of grade Ⅲ ( P=0.005), and TTP of grade Ⅰ was higher than that of grade Ⅲ ( P=0.015). There was no statistical significance of other indicators in pairwise comparison. There were no significant differences in CBV and DLY among collateral compensation grade Ⅰ, grade Ⅱ and grade Ⅲ ( P>0.05). Conclusions:4D CTA-CTP is equivalent to DSA in evaluating collateral circulation in patients with moyamoya disease and moyamoya syndrome. It can also evaluate the cerebral hemodynamics comprehensively, which has high clinical significance for disease monitoring.
7.Calculation method and empirical analysis of the total amount of price adjustment in medical service price reform
Changsong JIANG ; Lanting LYU ; Ting JIANG ; Peng QI ; Dan GUO ; Na LI ; Xin WANG ; Ximeng ZHAO
Chinese Journal of Hospital Administration 2023;39(7):475-479
In order to further promote the reform of medical service price and strengthen the macro management of medical service price, the author constructed a calculation method for price adjustment space of medical service. This study was centered on two parameters of the historical base and the growth coefficient, to calculate the total amountof price adjustment. The historical base used the total revenue of medical services in the region from the previous year, and the growth coefficient was measured by two methods, the comprehensive indicator method and the consumer price index (CPI) reference method.Taking Suzhou, a national pilot city, as an example, the historical base in 2022 was 18 754 million yuan. By using the comprehensive indicator method, the annual growth coefficient was calculated to be 2.38%, and adjustment space of medical service price was 446.35 million yuan; According to the CPI reference method, the growth coefficient of Suzhou was 2.10%, and adjustment space of medical service price was 393.83 million yuan.The two methods for calculating the total amount each have their own advantages and disadvantages, and need to be further optimized and improved by drawing on the practical experience of reform in each pilot city.
8.Construction of the evaluation index system on the mechanism of medical service price reform
Ting JIANG ; Changsong JIANG ; Lanting LYU ; Dan GUO ; Peng QI ; Na LI ; Ximeng ZHAO ; Youli HAN
Chinese Journal of Hospital Administration 2023;39(7):480-485
Objective:To design a set of evaluation index system for the medical service price reform mechanism, so as to provide reference for the evaluation of deepening the medical service price reform mechanism.Methods:On the basis of searching literature of medical service prices reformfrom August 2021 to March 2023, policy logic analysis and expert consultation were used to construct evaluation indexes for the medical service price reform mechanism, set evaluation index thresholds, and assign scores to index thresholds in different grades.Results:The evaluationindex system of medical service price reform mechanism included 5 level-1 indexes, 12 level-2 indexes and 35 level-3 indexes. After scoring, the scores of 5 level-1 indexes were 12, 24, 35, 21, and 8, respectively.Based on the percentile scoring method, the evaluation criteria were categorized into five grades: premium, excellent, good, average and failure.Conclusions:This study constructed a set of evaluation index system for the mechanism of medical service price reform, which had strong scientific and operability. However, due to the fact that medical service price reform in the new era is still in its initial stage, the index system need to be further optimized drawing on the practical experience of reforms in pilot cities.
9.To explore the mechanism of tripterygium wilfordii-white peony in rheumatoid arthritis based on network pharmacology and animal experiments
Fangze LI ; Lei WAN ; Lei ZHAO ; Ziheng ZHU ; Ximeng MA ; Shu LI ; Saisai HU ; Jing CHENG ; Yingying CHEN
China Modern Doctor 2023;61(36):95-100,111
Objective Using network pharmacology to explore the mechanism of action of tripterygium wilfordii-white peony in the treatment of rheumatoid arthritis(RA)and validating it using an adjuvant arthritis rat model.Methods Obtain the effective ingredients of tripterygium wilfordii and white peony through TCMSP database and predict the action targets;Obtain the disease targets of RA using DisGeNET and GeneCards online database;Draw the network of"tripterygium wilfordii-white peony-active ingredient-RA"and screen the core effective components using the software Cytoscape 3.9.1;Construct the protein-protein interaction(PPI)network using String database and screen the core targets using the CytoNCA plug-in,using the Metascape database for gene enrichment analysis of common targets,and using Auto Dock Tools and Pymol software for molecular docking of core active ingredients and targets.Enzyme linked immunosorbent assay(ELISA)detection of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-17 levels in adjuvant arthritis rats,Western blot was used to detect the expression of phosphorylated phosphatidylinositol 3-hydroxy kinase(p-PI3K)and phosphorylated AKT protein(p-AKT),validate the results of network pharmacology analysis.Results There were a total of 61 effective ingredients in the treatment of RA with tripterygium wilfordii-white peony,with 116 targets and 191 signaling pathways involved.Animal experiments have shown that compared with the model group rats,the serum cytokine TNF-α,IL-6 and IL-17 of rats in tripterygium wilfordii-white peony group and tripterygium wilfordii extract group were significantly decreased(P<0.05),IL-4 significantly increased(P<0.05);The expression of p-PI3K and p-AKT in synovial tissue was significantly reduced(P<0.05);Compared with rats in tripterygium wilfordii extract group,the TNF-α,IL-6,IL-17,p-PI3K and p-AKT of rats in tripterygium wilfordii-white peony group were significantly reduced(P<0.05),while IL-4 was significantly increased(P<0.05).Conclusion Tripterygium wilfordii-white peony can inhibit the overexpression of phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathway,regulate cytokine release,exert anti-inflammatory effects,and ultimately treat RA through multiple active ingredients and targets.
10.Risk factor of the growth rate of cerebral infarction and its effects on the prognosis in elderly patients with acute ischemic stroke
Ling LI ; Rui WANG ; Hong WANG ; Ruoyao CAO ; Yao LU ; Zilong YOU ; Ximeng YANG ; Jing HE ; Juan CHEN
Chinese Journal of Geriatrics 2022;41(4):417-422
Objective:To investigate the risk factors of infarct growth rate of elderly acute ischemic stroke(AIS)patients with endovascular treatment(EVT)and its influence on prognosis.Methods:Elderly AIS patients who underwent EVT at Beijing hospital from June 2016 to October 2020 were retrospectively included.Infarct growth rate(ml/h)=infarct core volume(ml)/time from stroke onset to CTP examination(h).Based on the rate of infarct growth and the patient's clinical severity, ROC curve was established, and the cut-off value of the ROC curve was obtained.By the cut-off value of the rate of infarct growth, the patients were divided into cerebral infarct slow-growth group and rapid-growth group.Predictors of rapid growth in infarct were analyzed by univariate and multivariate analysis.The patients were divided into good prognosis group(mRS score 0-2)and poor prognosis group(mRS score 3-6)according to the mRS score at the day 90 and the predictors of poor prognosis were analyzed separately.Results:A total of 67 elderly AIS patients were included with age ranging from 65-96 years and an average of(78.8±7.6)years.(1)The cut-off value of the optimal infarct growth rate for patients with good and poor prognosis was 8.89 ml/h.The patients were divided into fast-growth group(26 patients)and slow-growth group(41 patients)according the cut-off value.(2)Multivariate logistic regression showed that only poor collateral circulation was an independent predictor for fast infarct growth( OR=0.162, 95% CI: 0.053-0.489).(3)Faster infarct growth rate( OR=1.173, 95% CI: 1.044-1.318)and high NIHSS score( OR=1.146, 95% CI: 1.018-1.291)were predictors of poor prognosis. Conclusions:Collateral circulation status is a major influencing factor for the infarct growth rate, and a faster infarct growth rate is a predictor of poor prognosis for elderly AIS patients after endovascular treatment.


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