1.Curculiginis Rhizoma Ameliorates Kidney-Yang Deficiency in Castrated Rats via PI3K/Akt Signaling Pathway
Meng YANG ; Lu WANG ; Zijia ZHANG ; Zhengtao WANG ; Ying XU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):46-53
ObjectiveTo study the effect and mechanism of Curculiginis Rhizoma in ameliorating kidney-Yang deficiency in castrated rats. MethodThe targets of Curculiginis Rhizoma and male reproductive diseases due to kidney-Yang deficiency were screened from relevant databases by network pharmacology, and key targets were screened out according to topological eigenvalues. After that, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to obtain the pathways of Curculiginis Rhizoma in treating kidney-Yang deficiency. The rat model of kidney-Yang deficiency was established by castration. The rats were assigned into model, testosterone propinate (2 mg·kg-1), and low-, medium-, high-dose (0.14, 0.28, 0.56 g·kg-1, respectively) Curculiginis Rhizoma groups. Another 8 healthy male rats with first incising and then suturing were used as the sham group. The rats were administrated with corresponding agents by gavage once a day for 6 consecutive weeks. During the experiment, the general conditions of rats in each group were observed, and their body mass was recorded. At the end of the experiment, the indexes of accessory sex organs were calculated, and the pathological changes of the seminal vesicle glands and prostate glands were observed by hematoxylin-eosin (HE) staining. The serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay. The results of the network pharmacological prediction were verified by animal experiments, and the expression levels of related genes and proteins were determined by real-time polymerase chain reaction and Western blot, respectively. ResultThe biological functions enriched mainly involved four overexpression modules including regulation of cell responses to various stimuli, metabolic responses, regulation of intracellular signal transduction, and regulation of reproduction. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was a significantly enriched pathway for the core target and also a pathway with the highest enrichment factor in the biological process of regulating cell responses to stimuli. The results of animal experiments showed that compared with the model group, low-dose Curculiginis Rhizoma group increased the body weight gain (P<0.05). In addition, high-dose Curculiginis Rhizoma group increased the seminal vesicle gland index and epididymis index (P<0.05). The administration with Curculiginis Rhizoma ameliorate epithelial cell hyperplasia of the seminal vesicle glands, did not attenuate the vacuolar degeneration, mitigated the enlarged vesicular lumen of the prostate gland, changing of epithelial cells of the glands from flattened to cubic and columnar shapes, and cellular disarrangement, and reduced the mesenchymal stroma thickness. Compared with the model group, all the intervention measures elevated the levels of FSH, LH, T, and IL-6 (P<0.05, P<0.01) and up-regulated the mRNA and protein levels of PI3K and the mRNA levels of Akt in the epididymis tissue (P<0.05). ConclusionCurculiginis Rhizoma can alleviate the T level reduction and accessory sex organ atrophy in castrated rats by regulating the PI3K/Akt signaling pathway.
2.Analysis of the current sitnation and influencing factors of nurses ′ ethical competence
Junhui XU ; Yue MA ; Nan ZHANG ; Lili HAO ; Jing WANG ; Yan ZHANG ; Junkun BAN ; Zhengtao ZHANG
Chinese Journal of Practical Nursing 2024;40(24):1903-1909
Objective:To understand the current state of ethical competence levels of nurses and analyse the factors that influence them, in order to inform the development of targeted training programmes.Methods:This study adopted a cross-sectional survey method and used convenience sampling to select 825 clinical nurses from Tianjin Chest Hospital as the survey objects from July to August, 2023, and a questionnaire survey was conducted using the General Information Questionnaire, the Ethical Competence Scale, Ethical Competence Support Scale, and Ethical Safety Scale.Results:A total of 818 valid questionnaires were retracted. Among the 818 nurses, 48 were males and 770 were females, the age was (33.19 ± 7.40) years. The total score of nurses ′ Ethical Competence, Ethical Competence Support and Ethical Safety were (118.08 ± 19.96), (215.07 ± 32.02), (48.93 ± 7.55) points, all of which were at a high level. The total score of nurses ′ ethical competence were positively correlated with ethical competence support and ethical safety ( r=0.856, 0.830, both P<0.01); multivariate linear regression analysis showed that the department, the level of ethical competence support, and the level of ethical safety were the influencing factors of the level of ethical competence ( t=5.19, 12.35, 3.88, all P<0.01). Conclusions:Nurses ′ ethical competence, ethical competence support, and ethical safety were at a high level, and the department, the level of ethical competence support, and the level of ethical safety were the factors influencing the level of ethical competence. Nursing managers can provide more ethical education and address ethical issues in multiprofessional discussions, strengthen organizational and personal support for nurses ′ ethical competence, improve nurses ′ ethical safety, and help them implement good ethical care.
3.Relationship between the expression of KLF5 and KDM2A in cancer tissues of patients with oral cancer and clinicopathological characteristics and prognosis
Tao WANG ; Zhengtao YANG ; Yingliang LIN
International Journal of Laboratory Medicine 2024;45(15):1805-1810
Objective To investigate the relationship between the expression of Krüppel-like factor 5(KLF5)and lysine demethylase 2A(KDM2A)in cancer tissues of patients with oral cancer and clinicopatho-logical characteristics and prognosis.Methods Cancer tissues of 80 patients with oral cancer who underwent surgical treatment in the Zigong First People's Hospital from January 2015 to January 2018 were retrospec-tively collected as research objects,and normal adjacent tissues were selected as controls.The expression of KLF5 and KDM2A in cancer tissues and adjacent tissues of patients with oral cancer was detected by immuno-histochemical staining,and the correlation between KLF5 and KDM2A in cancer tissues was analyzed by Spearman correlation.Clinicopathological features of patients with oral cancer were collected,and the relation-ship between the expression of KLF5 and KDM2A in cancer tissues and clinicopathological features of patients was analyzed,as well as the prognostic factors of patients with oral cancer were analyzed by multivariate Cox regression.Kaplan-Meier method was used to analyze the relationship between the expression of KLF5 and KDM2A and the prognosis of patients with oral cancer.Results The high expression rates of KDM2A and KLF5 in oral cancer tissues were significantly higher than those in adjacent tissues,and the difference was sta-tistically significant(P<0.05).Spearman correlation analysis showed that there was a positive correlation be-tween KLF5 and KDM2A expression in oral cancer patients(r=0.375,P<0.05).The expressions of KLF5 and KDM2A in patients with oral cancer were correlated with TNM stage,clinical stage,lymph node metasta-sis,local invasion and differentiation degree(P<0.05).Multivariate Cox regression analysis showed that the expression level of KLF5 and KDM2A,TNM stage,lymph node metastasis,local invasion and differentiation degree were independent risk factors for poor prognosis in patients with oral cancer(P<0.05).The 5-year survival rates of patients with high expression of KLF5 and KDM2A in cancer tissues[38.88%(21/54),42.37%(25/59)]were lower than those of patients with low expression of KLF5 and KDM2A in cancer tis-sues[65.38%(17/26),61.90%(13/21)],the difference was statistically significant(x2=6.554,4.046,P<0.05).Conclusion The expression of KLF5 and KDM2A in cancer tissues of patients with oral cancer is high and affects the prognosis of patients.
4.Lower Limb Joint Torque Estimation Based on Depth Camera and Neural Network
Fei GAO ; Zhengtao WANG ; Dongmei WANG ; Suiran YU
Journal of Medical Biomechanics 2024;39(3):450-456
Objective To estimate the flexion and extension torques of the hip,knee,and ankle joints during straight-line walking using depth cameras and neural networks.Methods Gait information was collected from 20 individuals using an optical motion capture system,force plates,and an Azure Kinect depth camera.The subjects were asked to walk straight at their preferred speed while stepping on the force plates.The joint torques were obtained using visual 3D simulation as a reference value,and an artificial neural network(ANN)and long short-term memory(LSTM)network were trained to estimate the joint torques.Results The relative root mean square errors(rRMSEs)of the ANN model for estimating the joint torques of hip,knee,and ankle were 15.87%-17.32%,18.36%-25.34%,and 14.11%-16.82%,respectively,and the correlation coefficients were 0.81-0.85,0.69-0.74 and 0.76-0.82,respectively.The LSTM model had a better estimation effect,with rRMSEs of 8.53%-12.18%,14.32%-18.78%,and 6.51%-11.83%,and correlation coefficients of 0.89-0.95,0.85-0.91 and 0.90-0.97,respectively.Conclusions This study confirms the feasibility of using a depth camera and neural network for noncontact estimation of lower limb joint torques,and LSTM has a better performance.Compared with existing studies,the joint torque estimation results have better accuracy,and the potential application scenarios include telemedicine,personalized rehabilitation program development,and orthosis-assisted design.
5.Research Advances of Chemical Constituents and Analytical Methods of Shengmai Formula
Zixuan QIAN ; Xueyang SUN ; Chenming ZHANG ; Longchan LIU ; Linnan LI ; Haoyue ZHANG ; Li YANG ; Zhengtao WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(8):2699-2708
Shengmai formula,composed of Ginseng Radix et Rhizoma,Ophiopogon Radix and Schisandrae Chinensis Fructus,is a classic and famous formula.It is a representative formula for"supplementing qi,nourishing yin,and generating fluid"in Traditional Chinese Medicine theory.To date,a wide range of Shengmai formulae have been developed according to different medical applications,but the quality evaluation standards are at a relatively low level,and most of them only specify the individual components of a single herb,making it difficult to ensure clinical efficacy and safety.At the same time,the physical and chemical identification methods of Shengmai formula have been constantly updated,allowing for greater progress in research on its main chemical components such as saponins,lignans and flavonoids.However,there is little systematic summarization of the chemical components and analytical methods.Based on the existing references,we systematically summarized ginsenosides,ophiopogonins,schisandra lignans,homoisoflavonoids and some other compounds in this paper,as well as the quality standards of Shengmai formulae and their analytical methods in order to aid clinical research and formulation manufacture.
6.Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones:From analytical method development towards application to clinical samples
Jiaojiao WEI ; Tao CHEN ; Yamin LIU ; Shuai SUN ; Zhiqing YUAN ; Yixin ZHANG ; Aizhen XIONG ; Linnan LI ; Zhengtao WANG ; Li YANG
Journal of Pharmaceutical Analysis 2023;13(9):1080-1087
Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.
7.Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation
Xiaoxu KONG ; Zhihua FENG ; Xuejia WANG ; Ganghua HE ; Ting PAN ; Zhengtao XU ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Chinese Journal of Radiological Medicine and Protection 2023;43(5):328-334
Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.
8.Prevention and Treatment of Diabetic Nephropathy by Regulating Endoplasmic Reticulum Stress with Traditional Chinese Medicine: A Review
Zhengtao CHEN ; Qingzhi LIANG ; Yuan ZHANG ; Yan YANG ; Mengping WANG ; Chunguang XIE ; Hong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):227-239
Diabetic nephropathy (DN) is one of the serious and common microvascular complications of diabetes mellitus (DM) and the main cause of end-stage renal disease (ESRD). Endoplasmic reticulum stress (ERS) is a common stress defense mechanism in eukaryotic cells. In the ERS state, cells activate the unfolded protein response (UPR) to enhance the folding of unfolded proteins and the degradation of misfolded proteins, so as to restore the normal physiological function of the endoplasmic reticulum and avoid cell damage. However, excessive or chronic persistent ERS can induce apoptosis, inflammation, oxidative stress and other pathways to eventually cause cell damage. In recent years, a large number of studies have confirmed that ERS is closely associated with the occurrence and development of DN. In the case of DN, ERS is involved in the damage or protection of podocytes, glomerular mesangial cells, renal tubular epithelial cells, and glomerular endothelial cells. The regulation of ERS has become one of the hotspots in the prevention and treatment of DN and has received extensive attention in the field of traditional Chinese medicine. This paper systematically expounds the role of ERS in the occurrence and development of DN and summarizes the ERS-targeted regulation of DN by traditional Chinese medicine, with a view to providing certain research ideas for the prevention and control of DN with traditional Chinese medicine.
9.Quality Evaluation and Suggestions on Pharmacopoeia Standard of Eucommiae Folium
Ping WANG ; Shaojia LIANG ; Wenwen ZHANG ; Weihong FENG ; Hong YI ; Chun LI ; Fengqian GUO ; Qin SI ; Dejing FU ; Man GONG ; Zhengtao WANG ; Hongchu ZHENG ; Xiaoqian LIU ; Zhimin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):10-17
ObjectiveTo establish a quantitative analysis multi-components by single marker method (QAMS) for five main components (aucubin, geniposidic acid, chlorogenic acid, asperuloside and rutin) in Eucommiae Folium, to verify its feasibility and applicability in the determination of Eucommiae Folium, so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C18 column (4.6 mm×100 mm, 2.7 μm) with methanol (A)-0.2% phosphoric acid aqueous solution (B) as the mobile phase for gradient elution (0-8 min, 3%A; 8-10 min, 3%-11%A; 10-26 min, 11%A; 26-27 min, 11%-25%A; 27-60 min, 25%-32%A), the column temperature was set at 30 ℃, the flow rate was 0.6 mL·min-1, the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors (f) between it and the other four components, and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method (ESM), respectively. ResultThe f values of chlorogenic acid to aucubin, geniposidic acid, asperuloside and rutin were 3.13, 1.45, 2.64 and 0.56, respectively. Repeatability was good under different experimental conditions, relative standard deviation (RSD) was <5.0%. The contents of aucubin, geniposidic acid, chlorogenic acid, asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975, 0.252-36.086, 10.016-27.443, 1.396-8.646, 0.533-1.766 mg·g-1, respectively. There were no significant difference between content results of QAMS and that of ESM (RSD<5.0%). ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium, and this method is simple and accurate. After comprehensive evaluation, the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components, chlorogenic acid, aucubin and geniposidic acid, are selected as quality markers, and their content limits are recommended not less than 1.5%, 1.0% and 1.0%, respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component (chlorogenic acid) in the previous editions of Chinese Pharmacopoeia.
10.Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial-mesenchymal transition via directly targeting TGFβR1.
Jingnan ZHANG ; Ze ZHANG ; Zhenlin HUANG ; Manlin LI ; Fan YANG ; Zeqi WU ; Qian GUO ; Xiyu MEI ; Bin LU ; Changhong WANG ; Zhengtao WANG ; Lili JI
Acta Pharmaceutica Sinica B 2023;13(7):2990-3007
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

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