1.Rapid Identification of Different Parts of Nardostachys jatamansi Based on HS-SPME-GC-MS and Ultra-fast Gas Phase Electronic Nose
Tao WANG ; Xiaoqin ZHAO ; Yang WEN ; Momeimei QU ; Min LI ; Jing WEI ; Xiaoming BAO ; Ying LI ; Yuan LIU ; Xiao LUO ; Wenbing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):182-191
ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi, so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS) combined with Smart aroma database and National Institute of Standards and Technology(NIST) database were used to characterize the aroma components in different parts of N. jatamansi, and the aroma components were quantified according to relative response factor(RRF) and three internal standards, and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis(OPLS-DA) and cluster thermal analysis based on variable importance in the projection(VIP) value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose, and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data, and the rapid identification model of different parts of N. jatamansi was established by principal component analysis(PCA), discriminant factor alysis(DFA), soft independent modeling of class analogies(SIMCA) and statistical quality control analysis(SQCA). ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi, of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components, the contents of five components(ethyl isovalerate, 2-pentylfuran, benzyl alcohol, nonanal and glacial acetic acid,) in the aboveground part of N. jatamansi were significantly higher than those in the underground part(P<0.01), the contents of β-ionone, patchouli alcohol, α-caryophyllene, linalyl butyrate, valencene, 1,8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part(P<0.01). Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82, and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted, respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%, the validation score of the SIMCA model for discrimination of the two parts was 99, and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose(PCA, DFA, SIMCA and SQCA) can realize the rapid identification of different parts of N. jatamansi. Combining the two results, it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.
2.Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules.
Ge SONG ; Minghui LI ; Shumin FAN ; Mengmeng QIN ; Bin SHAO ; Wenbing DAI ; Hua ZHANG ; Xueqing WANG ; Bing HE ; Qiang ZHANG
Acta Pharmaceutica Sinica B 2024;14(2):836-853
Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.
3.Regulating PI3K/Akt Signaling Pathway by Traditional Chinese Medicine to Improve Cognitive Impairment: A Review
Feifei LIU ; Yan ZHONG ; Liping CHEN ; Xiwen CHANG ; Wenbing LI ; Rong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):281-289
Cognitive impairment refers to the abnormality of the hippocampus, cortex and other parts of the brain, which is manifested by the decline of cognitive abilities such as learning, memory and attention. With the increase in people's work pressure and bad living habits, the incidence of cognitive impairment is getting higher and higher, which seriously affects people's normal life. However, there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore, the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine (TCM) has the characteristics of "multi-component, multi-pathway and multi-target", and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress, inflammation, apoptosis, autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signal pathway plays an important role in the transmission of intracellular and intracellular signals, and in the regulation of cellular inflammation, apoptosis, autophagy, etc. TCM monomers, TCM extracts, and TCM compounds exert anti-inflammatory, antioxidant, anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway, and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress, inflammation, apoptosis and autophagy of neurons. Finally, the recent research status of the regulation of this signaling pathway by TCM extracts, TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.
4.Breast cancer phenotype affects accuracy of MRI response evaluation after neoadjuvant chemotherapy
Zhuanzhuan GUO ; Bing ZHANG ; Li ZHANG ; Zhe LEI ; Wenbing LIANG ; Quanxin YANG ; Xin CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):552-559
Objective To evaluate which factors may affect magnetic resonance imaging(MRI)performance in the detection of pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC).Methods This retrospective study involved 89 patients diagnosed with invasive breast carcinoma who received NAC at The Second Affiliated Hospital of Xi'an Jiaotong University from July 2019 to December 2021.Breast MRI was performed before and after NAC.Based on the pathological results obtained surgery after the completion NAC and using Miller-Payne classification as the evaluation standard,the patients were divided into two subgroups:pCR and non-pathological complete response(npCR).Chi-square test was used to compare the MRI characteristics of pre-NAC lesions between the two groups.ROC curve analysis was made to analyze the accuracy,sensitivity,specificity,positive predictive value,and negative predictive value of MRI after NAC;the diagnostic performance of MRI in predicting pCR in different tumor subtypes was analyzed.We made univariate and multivariate analyses of factors affecting radiographic complete response(rCR)and pCR concordance.Results MRI analysis after NAC showed rCR in 20 cases(22.5%)and pCR in 28 cases(31.5%).Considering rCR as a"positive"result of MRI analysis,MRI assessment was accurate in 79 cases,including 19 true positive cases and 60 true negative cases.MRI assessment was inaccurate in 10 cases,including 9 false negative cases and 1 false positive case.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MRI assessment of pCR were 67.86%,98.36%,88.76%,95.00%,and 86.96%.MRI had the lowest diagnostic efficiency in evaluating pCR of ERBB2+breast cancer after NAC.Single factor analysis showed that estrogen receptor(ER),clinical stage,background parenchymal enhancement,and maximum tumor diameter all affected the consistency of rCR and pCR(P<0.05).Multivariate Logistic regression analysis showed that the independent influencing factor affecting the consistency of rCR and pCR was clinical stage.Conclusion MRI demonstrated good accuracy in predicting pCR after NAC in the breast cancer patients examined.Pre-treatment MRI characteristics and tumor subtypes may be related to the diagnostic accuracy of post-NAC MRI in breast cancer patients.
5.Sophora davidii Hance leaves total alkaloids Attenuate Lipopolysaccharide-induced inflammatory response in RAW264.7 cell by Inhibiting the MAPK/NF-κB signaling pathway
Shengnan JIANG ; Wenbing ZHI ; Jing CHEN ; Tingting SUN ; Zongren XU ; Shuai LIU ; Hong ZHANG ; Ye LI ; Yang LIU
The Journal of Practical Medicine 2024;40(20):2835-2840
Objective To investigate the in vitro anti-inflammatory effects of Sophora davidii Hance leaves total alkaloids(SDLTAs)and possible molecular mechanisms.Methods The lipopolysaccharide(LPS)-induced inflammation model of RAW264.7 cells was used,and different concentrations of SDLTAs(50,100 and 200 μg/mL)were administered,and the effect of SDLTAs on cellular NO expression was detected by the Griess method;ELISA method was used to detect the effect of SDLTAs on the expression of IL-6,TNF-α and IL-1β;The expression of iNOS,NF-κB p65 and IκBα mRNA was detected by RT-qPCR;Western blotting was used to detecte the expres-sion of p-p38,p-p65 and p-JNK in the cells and NF-κB p65 in the nucleus.Results SDLTAs could significantly inhibit the LPS-induced inflammatory response in RAW264.7 cells.SDLTAs significantly decreased the secretion of NO,IL-6,TNF-α and IL-1β in cells(P<0.01),and significantly decreased the mRNA expressions of iNOS,NF-κB p65 and IκBα in cells(P<0.01).Significantly decreased the protein expression of p-p38,p-p65 and p-JNK in cells and NF-κB p65 in nucleus(P<0.01).Conclusion SDLTAs can exert anti-inflammatory effects by regulating the MAPK/NF-κB signalling pathway.
6.Deep learning for volumetric assessment of traumatic cerebral hematoma
Diyou CHEN ; Xinyi SHI ; Pengfei WU ; Li ZHAN ; Wenbing ZHAO ; Jingru XIE ; Liang ZHANG ; Hui ZHAO
Journal of Army Medical University 2024;46(19):2225-2235
Objective To develop a deep learning method for volumetric assessment of traumatic intracerebral hemorrhage(TICH)using the Trans-UNet model and to compare its performance with traditional formula-based methods.Methods CT data from 141 TICH patients admitted to Army Medical Center of PLA between May 2018 and May 2023 were collected.A deep learning method based on the Trans-UNet model was established.Manual delineation via picture archiving and communication system(PACS)was served as the gold standard for comparing the accuracy,consistency,and time efficiency of our method against 10 different formula-based methods for measuring the amount of TICH.Results The median volume of TICH,as manual delineation via PACS,was 1.167 mL,with a median measurement time of 135 s per patient.The median percentage error in volume between the deep learning method and manual delineation via PACS was 3.59%.Spearman correlation coefficient was 0.999(P<0.001),and a median measurement time was only 4.38 s per patient.In contrast,in the formula-based methods,the lowest median percentage error in volume was 16.451%,the highest Spearman correlation coefficient was 0.986(P<0.001),and the lowest median measurement time was 20 s for a single patient.The statistical differences were observed in percentage error in volume and measurement time between the 2 types of methods(all P<0.001).Conclusion Our developed deep learning method for volumetric assessment of TICH is superior to the formula-based methods in terms of measurement accuracy and time efficiency.
7.Ethical Considerations on Clinical Transformation of MSC-Exo in Tumor Therapy
Xiaoyan FAN ; Wenbing MA ; Xiao MA ; Jipeng LI
Chinese Medical Ethics 2023;36(10):1103-1109
In recent years, basic scientific research and clinical studies on mesenchymal stem cell-derived exosome (MSC-Exo) have developed rapidly. MSC-Exo has shown good anti-tumor effects in preclinical and clinical studies. However, due to its diverse sources and functions, MSC-Exo therapy still faces many ethical issues in clinical conversion and application, including the unclear tumor types and mechanisms of action applicable to MSC-Exo, the risk/benefit issues in the process of clinical research, the lack of safety/effectiveness evaluation standards, lax access standards, and the incomplete regulatory systems. The technical guidelines and regulatory policies related to the clinical transformation and application of stem cell therapy are constantly improving. Therefore, to effectively avoid ethical risks, regulate the research and treatment related to the clinical transformation and application of MSC-Exo therapy, and improve the safety and efficacy of MSC-Exo therapy in tumor therapy, it is proposed to deepen clinical research on the relationship between MSC-Exo and tumor regulation, strengthen the risk/benefit analysis, supervise and improve the professional quality of researcher, deeply root in the principle of subjects not to be harmed, construct and perfect the relevant regulatory system, and improve the reviewing ability of the ethics committee, so as to promote the rapid clinical transformation of MSC-Exo and bring good news to cancer patients.
8.Discussion on Development Status of Traditional Chinese Medicine Dispensing Granules and Survival Strategy of Enterprises
Tao WANG ; Shuqi LIU ; Yaohong LI ; Zhengming YANG ; Xinjia YAN ; Houcheng ZHOU ; Wenbing LI ; Shilin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):166-173
As an important complementary form of decoction pieces of traditional Chinese medicine(TCM), TCM dispensing granules has the advantages of being free of decoction, easy to take, easy to carry and easy to be dispensed, which greatly improves the capacity of emergency services of TCM and is more in line with the needs of modern society. With the end of the pilot project of TCM dispensing granules, the market has been fully liberalized, the competition has been intensified, and it is in the transition period of switching between the new standard and the old one, and there are some problems such as the shortage of varieties, the change of specifications and the difference of quality, and the production enterprises are facing new opportunities and challenges. Based on this, the authors intend to systematically sort out the policies and regulations, enterprise layout and standard formulation since the pilot of TCM dispensing granules. In view of the problems in the post-pilot stage and from the perspective of survival and development of enterprises, it is suggested that enterprises should establish a quality control system for the whole industry chain of TCM dispensing granules to reduce process costs and increase enterprise competitiveness, further increase the investment in scientific research, overcome the key technical problems of difficult varieties, actively and orderly promote the research of national standards, in order to ensure the integrity of clinical formula varieties, and establish and improve the efficacy evaluation mechanism of TCM dispensing granules, build a consistency evaluation system between TCM dispensing granules and decoction pieces. Government departments should strengthen the guidance, fully mobilize the enthusiasm of scientific research institutions, enterprises and hospitals, and explore the establishment of "government-industry-study-research-application" mode to promote the development of TCM dispensing granule industry.
9.Effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating Rho/ROCK1 pathway
Dongxu FENG ; Wei WU ; Pingfa GAO ; Jun WANG ; Lijuan SHI ; Dawei CHEN ; Wenbing LI ; Meifeng ZHANG
Journal of International Oncology 2023;50(8):449-456
Objective:To explore the effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating the Rho/ROCK1 pathway.Methods:Breast cancer MCF7 cells were divided into breast cancer cells (BC) group, breast cancer cells + miR-451-NC (MN) group, breast cancer cells + miR-451 inhibitor (MI) group, breast cancer cells + miR-451 mimic (MM) group, breast cancer cells + lysophosphatidic acid (BL) group, breast cancer cells + fasudil (BF) group, and breast cancer cells + miR-451 mimic + fasudil (MF) group. Glucose uptake detection kit and lactate detection kit were used to detect cell glycolysis, DAPI staining was used to detect cell apoptosis, Western blotting was used to detect Rho/ROCK1 pathway protein expression, and double luciferase reporting assay was used to confirm the interaction between miR-451 and Rho/ROCK1.Results:The glucose intake of cells in the BC group, MN group, MI group and MM group were (14.22±2.36) ×10 5 mg/h, (14.20±2.37) ×10 5 mg/h, (21.55±2.43) ×10 5 mg/h, (6.19±1.34) ×10 5 mg/h ( F=5.30, P<0.001), respectively, and lactic acid production were (1.52±0.21) ×10 5 μg/h, (1.53±0.22) ×10 5 μg/h, (2.05±0.32) ×10 5 μg/h, (0.54±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (10.16±1.37) %, (5.36±1.24) %, (28.47±2.56) % ( F=6.36, P<0.001), respectively. The expressions of Rho protein were 2.31±0.46, 2.32±0.41, 2.95±0.35, 1.05±0.25 ( F=2.86, P=0.017), respectively. The expressions of ROCK1 protein were 2.51±0.41, 2.52±0.42, 3.05±0.33, 1.15±0.13 ( F=2.43, P=0.035), and there were statistically significant differences between the MN and MI groups, MN and MM groups, MI and MM groups (all P<0.05). The glucose intake in the BC group, BL group and BF group were (14.22±2.36) ×10 5 mg/h, (21.54±2.40) ×10 5 mg/h, (6.20±1.35) ×10 5 mg/h ( F=5.33, P<0.001), respectively. Lactic acid production were (1.52±0.21) ×10 5 μg/h, (2.01±0.30) ×10 5 μg/h, (0.55±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (5.34±1.22) %, (28.44±2.54) % ( F=6.45, P<0.001). The expressions of Rho protein were 2.31±0.46, 2.94±0.45, 1.01±0.24 ( F=2.40, P=0.037), respectively, and the expressions of ROCK1 protein were 2.51±0.41, 3.08±0.42 and 1.13±0.12, respectively ( F=2.38, P=0.039). The pairwise comparisons among the three groups were statistically significant (all P<0.05). In the MF group, glucose intake was (3.21±0.89) ×10 5 mg/h, lactic acid production was (0.33±0.04) ×10 5 μg/h, apoptosis rate was (38.01±2.87) %, Rho protein expression was 0.55±0.14, and ROCK1 protein expression was 0.51±0.10. There were statistically significant differences among the MM group, BF group and MF group ( F=4.53, P=0.001; F=4.26, P=0.002; F=6.12, P<0.001; F=4.06, P=0.002; F=9.72, P<0.001), and there were statistically significant differences between the MF group and BF group (all P<0.05). Dual luciferase report showed that miR-451 transfection significantly decreased the luciferase activity of ROCK1-3'-UTR-WT (0.59±0.03 vs. 1.01±0.05, t=17.64, P<0.001), but had no significant effect on mutated genes (1.01±0.07 vs. 1.02±0.04, t=0.30, P=0.767) . Conclusion:Overexpression of miR-451 can significantly inhibit glycolysis of breast cancer cells and promote apoptosis of breast cancer cells, the mechanism of which may be related to inhibition of Rho/ROCK1 pathway.
10.Military application prospect analysis and U.S.Armed Forces research and development layout of synthetic biology
Wenbing MA ; Lijuan LI ; Lei WANG
Military Medical Sciences 2023;47(12):893-898,918
Synthetic biology not only has broad economic prospects and social benefits,but also has potential application value in the military field.In recent years,the U.S.Armed Forces has grasped the frontier hotspots of synthetic biology,carried out applied research of synthetic biology in the military field,and sought innovative breakthroughs in the fields of military materials,military energy,military medicine and military sensing.This paper analyzes the development of synthetic biology,the prospect of military application and the deployment of related science and technology of the U.S.Armed Forces for reference.

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