1.Quality evaluation of Sanzi powder based on quantitative analysis of multi-component combined with chemical pattern recognition and entropy weight-TOPSIS method
Rongjie LI ; Qian ZHANG ; Wei ZHANG ; Xinkui LI ; Yuxia HU ; Mengdi ZHANG ; Jing LIU ; Fang WANG ; Fengye ZHOU ; Jun LI
China Pharmacy 2025;36(15):1846-1851
OBJECTIVE To comprehensively evaluate the quality of Sanzi powder from different batches based on 12 components quantitative analysis combined with chemical pattern recognition and entropy weight-TOPSIS method. METHODS The contents of 12 components in 15 batches of Sanzi powder (No. S1-S15) were determined by HPLC-MS/MS, such as ethyl gallate, gallic acid, ferulic acid, corilagin, genipin-1-O-β-D-gentiobioside, toosendanin, geniposide, caffeic acid, methyl deacetylated coumarinate, tannic acid, rutin, quercetin. Cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were conducted on the assay results. Using variable importance projection (VIP) value>1 and P<0.05 as the evaluation criteria, the quality differential markers in Sanzi powder were screened. The entropy weight method was used to calculate the weight value, and TOPSIS method was used to rank the quality of 15 batches of Sanzi powder from superior to inferior. RESULTS The contents of the 12 components were 13.494-24.292, 2 069.608-3 188.100, 1.410-3.616, 1 065.030-2 630.584, 1 404.704-1 838.078, 101.640-354.268, 9 193.720-14 777.854, 1.240-5.060, 148.028-5 541.990, 4 261.422-5 607.438, 107.560- 195.512, 2.226-4.192 μg/g, respectively. The results of CA, PCA and OPLS-DA indicated that 15 batches of Sanzi powder could be clustered into two groups. Specifically, batches S3, S7, S10 and S15 were grouped into one category, and remaining batches were grouped into one category. VIP values of geniposide, quercetin, caffeic acid, and methyl deacetylated coumarinate were all greater than 1, with corresponding P-values less than 0.05. The results of the entropy weight-TOPSIS analysis revealed that methyl deacetylate exhibited the smallest information entropy and the highest weight. The relative closeness degrees of samples S3, S7, S10 and S15 ranged from 0.789 to 0.973, while the remaining samples ranged from 0.054 to 0.172. CONCLUSIONS The contents of 12 components in Sanzi powder could be determined accurately by using HPLC-MS/MS technology. Methyl deacetylated coumarinate, geniposide, quercetin and caffeic acid were identified as the quality differential markers. It was found that the overall quality of samples S3, S7, S10 and S15 were superior to that of other batches. Notably, the quality of Gardeniae Fructus decoction pieces emerges as a critical factor in ensuring the consistency of the preparation’s quality.
2.Effect of Cannabidiol on Pulmonary Fibrosis Analyzed by UPLC-Q-TOF-MS
Mengdi SUN ; Feiyu ZHANG ; Huicong YANG ; Yu WANG ; Pingping CHEN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):185-193
ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). MethodSD rats were randomly divided into blank group, model group, prednisone group(3.15 mg·kg-1) and cannabidiol low, medium and high dose groups(12, 36, 108 mg·kg-1), with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin(5 mg·kg-1), which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of matrix metalloproteinase-7(MMP-7), type Ⅱ alveolar cell surface antigen(KL-6), pulmonary surfactant-associated protein A(SP-A) and SP-D in serum. The expression levels of type Ⅰ collagen(Col-Ⅰ) and fibronectin(FN) in lung tissues were detected by immunohistochemistry, and the expression of mucin 5 subtype AC(MUC5AC) was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis. ResultCompared with the blank group, there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group, the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group, the expressions of MMP-7, KL-6, SP-A and SP-D in serum of the model group were significantly increased(P<0.01), while the expressions of MMP-7, KL-6, SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group(P<0.05, P<0.01). Compared with the blank group, the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased, and the fluorescence intensity of MUC5AC was significantly increased(P<0.01). Compared with the model group, the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased(P<0.05, P<0.01), and the expression of MUC5AC was significantly decreased(P<0.01). Compared with the blank group, a total of 18 differential compounds were screened out in the model group, which could be used as potential biomarkers, and cannabidiol could call back 16 of them, mainly involving 4 metabolic pathways(linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, and niacin and niacinamide metabolism). Compared with the blank group, the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group(P<0.05, P<0.01), while the relative contents of 5,6-EET, L-tyrosine and niacinamide were significantly decreased(P<0.01). Compared with the model group, cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid, and significantly increase the relative contents of 5,6-EET, L-tyrosine and niacinamide(P<0.01). ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis, and its mechanism may be related to linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, niacin and niacinamide metabolism.
3.Magnetic resonance left ventricular hemodynamic analysis: a normal value study of two methods
Huaying ZHANG ; Wenjing YANG ; Jing XU ; Di ZHOU ; Yining WANG ; Leyi ZHU ; Mengdi JIANG ; Gang YIN ; Shihua ZHAO ; Minjie LU
Journal of Chinese Physician 2024;26(1):12-17
Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.
4.Effect of esketamine on cognitive function in patients with major depressive disorder after electro-convulsive therapy
Mengdi XUE ; Zhiguo LI ; Shaoxing WANG ; Jiaxuan HUANG ; Yanqing ZHANG
The Journal of Clinical Anesthesiology 2024;40(7):723-726
Objective To investigate the effect of esketamine on depression and improvement of postoperative cognitive function in patients with major depressive disorder treated by electroconvulsive therapy(ECT).Methods A total of 115 patients with major depressive disorder,37 males and 78 fe-males,aged≥12 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ were selected to receive ECT.The patients were randomly divided into two groups using a random number table:the esketamine group(group E,n=56)and the control group(group C,n=59).Group E received esketamine,propofol,and succincholine during anesthesia induction,and group C received propofol and succincholine during an-esthesia induction.ECT indicators(including EEG twitch time,twitch time,stimulus intensity,and twitch energy index)were recorded during each ECT session.Montreal cognitive assessment(MoCA)and Mini-mental state examination(MMSE)were used to evaluate cognitive function at baseline and after ECT treat-ment.Hamilton depression(HAMD)scale was used to score depression.The occurrence of headache,nau-sea,vomiting,dizziness,delirium,and other adverse reactions were recorded.Results Compared with group C,the EEG convulsion time in group E was significantly prolonged(P<0.05),the incidence of Mo-CA score decreased by≥1 point and MMSE score decreased by≥1 point in group E after the end of ECT treatment was significantly reduced(P<0.05),the incidence of nausea,vomiting,and dizziness were sig-nificantly decreased(P<0.05).Conclusion Using esketamine in ECT for the treatment of major depres-sive disorder can improve cognitive function after ECT.
5.Exploring the Molecular Mechanism of Aconiti Kusnezoffii Radix Ameliorates Diabetes Mellitus Type 2 Based on Systems Pharmacology
Tingting LIU ; Yue WU ; Qi CHEN ; Fuhou CHANG ; Mengdi ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(5):606-618
OBJECTIVE
To explore the potential of Aconiti Kusnezoffii Radix in affecting diabetes mellitus type 2(T2DM) and the potential mechanism for T2DM related symptoms based on systematic pharmacology, bioinformatics, molecular docking and in vitro and in vivo experiments.
METHODS
The database was used to search the related chemical components of Aconiti Kusnezoffii Radix, predict the potential targets and intervene related diseases. The differential genes of T2DM relative healthy people were retrieved from GEO database, mapped with the action target of Aconiti Kusnezoffii Radix, and placed in DAVID database for biological function enrichment. The sensitivity of the target gene to T2DM was analyzed by one-way ANOVA, binary logistic regression analysis and ROC curve. The binding position and interaction force between chemical compounds of Aconiti Kusnezoffii Radix and target proteins were analyzed by molecular docking technology. The effect of Aconiti Kusnezoffii Radix and its chemical compounds on the expression of target protein was verified by T2DM model in vivo and in vitro.
RESULTS
Through database retrieval and analysis, 304 kinds of target related diseases(P value<0.05, FDR<0.05) were obtained, and T2DM with the highest degree value(Degree=59) was selected and analyzed. The 43 target genes were obtained from the intersection of differential genes in T2DM relatively healthy people and potential action targets of Aconiti Kusnezoffii Radix. A total of 9 genes with significant differences were obtained by one-way ANOVA, 5 meaningful genes were obtained by binary logistic regression analysis, and 3 genes with area under ROC curve AUC>0.5 were obtained. By molecular docking (+)-Isoboldine binds to proteins APEX1, CASP1 and CBFB, Napelline binds to proteins CBX1 and EHMT2 through different forces such as hydrogen bond interaction, ligand interaction, hydrophobic interaction, ionizability and electrostatic interaction, so as to increase the ability of ligands to target proteins. After 2 weeks of treatment with Aconiti Kusnezoffii Radix aqueous extract, Aconiti Kusnezoffii Radix may alleviated the symptoms of T2DM by improving peripheral neuropathy. Moreover, Aconiti Kusnezoffii Radix could affect the protein expression of APEX1, CASP1, CBFB, CBX1 and EHMT2 in rat liver tissue. The effect of (+)-Isoboldine and Napelline chemical compounds in Aconiti Kusnezoffii Radix on the target protein of the model in vitro was consistent with that in vivo.
CONCLUSION
It is preliminarily revealed that Aconiti Kusnezoffii Radix can be used as a potential therapeutic drug to improve T2DM peripheral neuropathy, which lays a theoretical foundation for the research and development of Chinese Mongolian medicine and the excavation of new target drugs for the treatment of T2DM.
6.Sanguinarine alleviates ulcerative colitis in mice by regulating the Nrf2/NF-κB pathway
Na ZHAO ; Mengdi SHEN ; Rui ZHAO ; Di AO ; Zetan LUO ; Yinliang ZHANG ; Zhidong XU ; Fangtian FAN ; Hailun ZHENG
Journal of Southern Medical University 2024;44(8):1467-1475
Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.
7.Global epidemiology of liver cancer 2022: An emphasis on geographic disparities
Qianru LI ; Chao DING ; Maomao CAO ; Fan YANG ; Xinxin YAN ; Siyi HE ; Mengdi CAO ; Shaoli ZHANG ; Yi TENG ; Nuopei TAN ; Jiachen WANG ; Changfa XIA ; Wanqing CHEN
Chinese Medical Journal 2024;137(19):2334-2342
Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.
8.Research progress in biological characteristics of dental pulp stem cells and their applications in treatment of corneal and retinal diseases
Xiangyu LIU ; Mengdi ZHANG ; Jixue WANG ; Chunling XU
Journal of Jilin University(Medicine Edition) 2024;50(6):1773-1779
Dental pulp stem cells(DPSCs)are a type of mesenchymal stem cells with broad application potential.Due to their multipotent differentiation capabilities and ease of access,DPSCs have become a focus of research in the field of ophthalmology.In recent years,DPSCs have shown the potential clinical applications in the treatment of corneal epithelial injuries and retinal degenerative diseases.DPSCs can promote the corneal epithelial regeneration and reconstruction by differentiating into the corneal epithelial cells and inhibiting the M1 macrophages.Additionally,DPSCs can differentiate into the retinal photoreceptor-like cells and retinal ganglion-like cells,replace original retinal neurons,secrete neurotrophic factors to mediate injury repair,promote retinal regeneration,and improve the original function of the retina.This article systematically reviews the relevant domestic and international literatures in recent years,discussing the biological characteristics of DPSCs and the research progress in their applieation in the treatment of corneal and retinal diseases,with the aim of providing insights and strategies for the study of DPSCs in translational medicine and ophthalmic-related diseases.
9.Study on molecular marker screening and evaluation of Rubi Fructus and its analogues
Mengdi ZHENG ; Lingling ZHANG ; Qi ZHANG ; Long GUO ; Xingjun WANG
International Journal of Traditional Chinese Medicine 2024;46(6):792-796
Objective:To standardize the origin of Rubi Fructus by using ITS2 and matK molecular markers to identify Rubi Fructus and its analogues. Methods:The ITS and matK sequences of Rubus chingii Hu, Rubus corchorifolius L.f., Rubus hirsutus Thunb., Rubus parvifolius L., Rubus buergeri Miq. and Rubus lambertianus Ser. were amplified and sequenced. The hidden Markov model was used to remove 5.8S and 28S from ITS sequences. A total of 25 ITS2 sequences were obtained. And a total of 22 matK sequences were obtained by proofreading by Glustal software. MEGA software was used for matK and ITS2 sequences analysis, intraspecific and interspecific genetic distances caculation, and neighbor joining (NJ) phylogenetic tree construction. ITS2 secondary structure was predicted by ITS2 database and aligned by 4Sale software. Profile neighbor-joining (PNJ) phylogenetic tree was constructed based on combined ITS2 sequence and its secondary structure by ProfDistS software. Results:An obvious barcoding gap between Rubi Fructus and its analogues was showed. The topological relationship between NJ tree and PNJ tree was consistent, and each taxon exhibits monophyly. The ITS2 secondary structure of Rubi Fructus was significant different from its analogues.Conclusions:It is recommended that both ITS2 and matK markers can serve as DNA barcodes for identifying Rubi Fructus and its analogues. The addition of ITS2 secondary structure information can enrich the identification results and provide theoretical support for resource research and variety selection of Rubi Fructus.
10.KAT8 promotes the proliferation of colorectal cancer cell lines by enhancing METTL3 expression
Pengju ZHANG ; Jie LI ; Mengdi ZHANG ; Shaoke SUN ; Yinzhe XU
Basic & Clinical Medicine 2024;44(7):931-939
Objective To investigate the role and mechanism of lysine acetyltransferase 8(KAT8)on the prolifera-tion of colorectal cancer cells.Methods The expression of KAT8 in cancerous tissues and adjacent tissues of color-ectal cancer patients was analyzed by RNA-seq data of TCGA database.Cell proliferation was detected by colony-forming unit assays and CCK8.The GEO database was used to analyze the differential genes of KAT8 knockdown cells and control cells and perform functional pathway enrichment analysis.In the colorectal cancer database hosted on cBioPortal,that conducted an analysis examining the correlation between KAT8 and genes in the regulation of N6-methyladenosine(m6A)modification.Western blot technique was employed to assess the protein expression lev-els of KAT8 and METTL3.Results Compared to human normal colorectal tissue,KAT8 was highly expressed in colorectal cancer(P<0.05).Knockdown or selective inactivation of KAT8 inhibited colorectal cancer cells prolifera-tion(P<0.05).In colorectal cancer cell lines,knocking down KAT8 reduced m6A modification levels(P<0.05).Knocking down KAT8 inhibited METTL3 expression(P<0.05).Over-expression of METTL3 reversed cell prolifera-tion which was inhibited by knockdown KAT8(P<0.05).Conclusions KAT8 facilitates the proliferation of color-ectal cancer cell lines through regulation of METTL3-mediated m6A modifications.


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