1.Network Pharmacology and Experimental Verification Unraveled The Mechanism of Pachymic Acid in The Treatment of Neuroblastoma
Hang LIU ; Yu-Xin ZHU ; Si-Lin GUO ; Xin-Yun PAN ; Yuan-Jie XIE ; Si-Cong LIAO ; Xin-Wen DAI ; Ping SHEN ; Yu-Bo XIAO
Progress in Biochemistry and Biophysics 2025;52(9):2376-2392
ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.
2.Comparison of the efficacy of TiRobot orthopaedic robot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures
Xing-Long ZHAO ; Jian-Jun SHEN ; Kang-Hu FENG ; Zhi-Wei CHEN ; Yuan-Long SI ; Xuan ZHANG ; Guan-De WANG ; Xiang HAI
China Journal of Orthopaedics and Traumatology 2024;37(2):129-134
Objective To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P>0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P<0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P<0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.
3.Analysis of application effect of orthopedic medical device intelligent acceptance equipment combined with UDI code in the management of orthopedic medical devices
Xiangjun WANG ; Hong YUAN ; Qin WANG ; Weiling HU ; Jiangtao SI ; Si SHEN ; Jiao JIN
China Medical Equipment 2024;21(5):166-170
Objective:To analyze the application effect of intelligent acceptance equipment for orthopedic medical equipment combined with medical device unique device identifier(UDI)code in the management of orthopedic medical devices.Methods:Based on the UDI code,the UDI application process of orthopedic medical devices was formulated,and all operations such as inspection and accurate billing of orthopedic medical devices were completed through the identification and comparison of intelligent acceptance equipment for orthopedic medical devices.A total of 8 317 orthopedic instruments used in orthopedic surgery in Wangjing Hospital of China Academy of Chinese Medical Sciences from September to December 2023 were selected.According to the different time of the implementation of intelligent acceptance equipment for orthopedic medical devices,the 4 072 orthopedic devices used from September to October 2023 was marked as before implementation and adopted the traditional management mode,the 4 245 orthopedic devices used from November 2023 to December 2023 were marked as before implementation and adopted the intelligent acceptance management mode.The management effect and incidence of adverse events were compared before and after the implementation of intelligent acceptance equipment for orthopedic medical devices.Results:The total effective rate of management after the implementation of intelligent acceptance equipment for orthopedic medical instruments was 98.78%,which was significantly higher than that before the implementation,the difference was statistically significant(x2=272.03,P<0.01).The total incidence of adverse events after the implementation of the intelligent acceptance equipment for orthopedic medical devices was 8.83%,which was significantly lower than that before the implementation,the difference was statistically significant(x2=281.38,P<0.01).Conclusion:The intelligent acceptance device combined with UDI code for orthopedic medical devices can achieve efficient distribution,accurate acceptance and billing,reduce the occurrence of adverse events,meet the requirements of the whole process traceability management of one thing and one code,and improve the management level orthopedic medical devices.
4.Rapid prediction of G protein-coupled receptor structures using nanoluciferase assay
Yu-ming ZHUANG ; Lu-lu GUO ; Guo-xing FANG ; Xin LUO ; Si-yuan SHEN ; Fan YANG ; Jiu-yao ZHOU
Acta Pharmaceutica Sinica 2023;58(5):1267-1274
Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.
5.Influence of patellofemoral joint degeneration on clinical outcomes after medial unicompartmental knee arthroplasty.
Limin WU ; Quan CHEN ; Haibo SI ; Yuangang WU ; Yi ZENG ; Mingyang LI ; Yuan LIU ; Bin SHEN
Chinese Medical Journal 2023;136(13):1539-1550
BACKGROUND:
Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA.
METHODS:
Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic.
RESULTS:
A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = -2.18, P < 0.01) and KSS (MD = -2.61, P < 0.01). The severity degree of PFJ degeneration had no additional adverse effect on the OKS, KSS, or revision rates. For mobile-bearing UKA, only lateral PFJ degeneration significantly decreased the OKS (MD = -2.21, P < 0.01) and KSS (MD = -2.44, P < 0.01). For fixed-bearing UKA, no correlation was found between PROMs/revision rates and PFJ degeneration.
CONCLUSION
For medial mobile-bearing UKA, slight to moderate degenerative changes in the PFJ, except lateral facet, did not compromise PROMs or revision rates. For medial fixed-bearing UKA, although it might not be conclusive enough, PROMs or revision rates were not adversely affected by PFJ degeneration (regardless of the facet).
Humans
;
Arthroplasty, Replacement, Knee
;
Patellofemoral Joint/surgery*
;
Treatment Outcome
;
Osteoarthritis, Knee/surgery*
;
Knee Prosthesis
;
Bone Diseases
;
Knee Joint/surgery*
;
Retrospective Studies
6.Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study.
Shu-Xian LYU ; Dong-Fang QIAN ; Yu-Fei FENG ; Cheng-Wu SHEN ; Lu-Bo GUO ; Jian-Tao LYU ; Peng-Fei JIN ; Ting LI ; Si-Yuan TAN ; Zi-Xuan ZHANG ; Lin HUANG ; Xue ZHONG ; Le-Qun SU ; Xin HU ; Xin HUANG ; Xue-Yan CUI
Journal of Geriatric Cardiology 2023;20(4):293-308
BACKGROUND:
Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.
METHODS:
In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.
RESULTS:
81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.
CONCLUSIONS
In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.
7.Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma.
Meng Meng JI ; Yi Ge SHEN ; Ji Chang GONG ; Wei TANG ; Xiao Qian XU ; Zhong ZHENG ; Si Yuan CHEN ; Yang HE ; Xin ZHENG ; Lin Di ZHAO ; Wei Lin ZHAO ; Wen WU
Chinese Journal of Hematology 2023;44(2):112-117
Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
Humans
;
Granulocyte Colony-Stimulating Factor/therapeutic use*
;
Hematopoietic Stem Cell Mobilization/methods*
;
Hematopoietic Stem Cell Transplantation
;
Heterocyclic Compounds/adverse effects*
;
Lymphoma/drug therapy*
;
Lymphoma, T-Cell/therapy*
;
Multiple Myeloma/drug therapy*
;
Retrospective Studies
;
Transplantation, Autologous
8.Current situation of acupuncture and moxibustion patents in China and abroad.
Si-Yuan ZHEN ; Yang LIU ; Man GAO ; Shen-Yi LU ; Hai-Yan LI
Chinese Acupuncture & Moxibustion 2023;43(3):362-366
The patents of acupuncture and moxibustion in China and abroad was analyzed, aiming to provide support for the innovative development of acupuncture industry. With the China Think Tank of Patent of Traditional Chinese Medicine and the PatSnap database as data sources, based on the mathematical statistics method, the application trend, legal status, patent types, transformation and distribution of major technical fields of acupuncture patents in China and abroad were analyzed. As a result, a total of 53,422 acupuncture patents were screened, involving 49 countries and 4 organizations. The patent types were mainly utility model patents. Although the application number of acupuncture patent had increased rapidly, the average patent conversion rate was generally low, approximately 4%. In the context of global economic integration, the acupuncture industry is developing at a high speed. It is suggested to take advantage of the "Belt and Road Initiative" to improve the international acceptance of acupuncture and moxibustion, adhere to the principle of attaching equal importance to the number and quality of patents, promote the in-depth cooperation of industry-university-research, and promote high-quality development of acupuncture and moxibustion.
Humans
;
Moxibustion
;
Acupuncture Therapy
;
China
;
Medicine, Chinese Traditional
;
Databases, Factual
10.Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway.
Ruo-Lin WANG ; Shu-Hua LIU ; Si-Heng SHEN ; Lu-Yong JIAN ; Qi YUAN ; Hua-Hui GUO ; Jia-Sheng HUANG ; Peng-Hui CHEN ; Ren-Fa HUANG
Chinese journal of integrative medicine 2023;29(10):875-884
OBJECTIVE:
To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI).
METHODS:
Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively.
RESULTS:
The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01).
CONCLUSION
CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.
Rats
;
Male
;
Animals
;
AMP-Activated Protein Kinases/metabolism*
;
Cordyceps/metabolism*
;
Rats, Sprague-Dawley
;
Kidney/pathology*
;
Acute Kidney Injury/metabolism*
;
Signal Transduction
;
TOR Serine-Threonine Kinases/metabolism*
;
Reperfusion Injury/metabolism*
;
Cytokines/metabolism*
;
Acute Lung Injury/drug therapy*
;
Mammals/metabolism*

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