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.Mineralogical studies on iron-containing mineral medicines, Haematitum and Limonitum.
Min LU ; Xiao-Fei WANG ; Cheng-Cheng WANG ; Jing-Xu CHEN ; Hang-Jie ZHU ; Juan LI ; Yan CAO
China Journal of Chinese Materia Medica 2025;50(5):1179-1186
Haematitum and Limonitum are two iron-containing mineral medicines included in the 2020 edition of the Chinese Pharmacopoeia. They have similar main components and major differences in their property, flavor, channel tropism, and clinical uses. In this study, we investigated the surface properties, mineral composition, mineral dissociation, elemental composition, and iron state of Haematitum and Limonitum to explore their mineralogical differences. Scanning electron microscopy(SEM), specific surface and porosity analyzer, X-ray diffractometer(XRD), X-ray photoelectron spectrometer(XPS), and advanced mineral identification and characterization system(AMICS) were used to analyze the mineralogy of Haematitum and Limonitum. The results showed that Haematitum had an angular surface with granular attachments and a specific surface area of 17.04 m~2·g~(-1). In comparison, Limonitum had a smooth and flat surface with a bundled acicular crystal structure and a specific surface area of 46.29 m~2·g~(-1). Haematitum consists of 31 detectable minerals containing 18 elements, with the major element, iron(44.5% Fe~(2+) and 55.5% Fe~(3+)) distributed in 17 minerals, including hematite, iron oxide, knebelite, siderite, and magnesioferrite. Limonitum consists of 32 detectable minerals containing 17 elements, with the major element, iron(14.5% Fe~(2+) and 85.5% Fe~(3+)) distributed in 19 minerals, including limonite, iron oxide, chlorite, and knebelite. In summary, the elemental composition of Haematitum and Limonitum does not differ greatly, but there are large differences in the mineral composition and iron state. The large specific surface area and strong adsorption capacity of Limonitum may be one of the mechanisms of its anti-diarrheal action. The Fe_2O_3 and illite contained in Haematitum and Limonitum may be the key substances for their hemostasis effects. The mineralogical differences are expected to provide a reference for explaining the scientific connotation of mineral medicine and laying a material foundation for studying its mechanism of action.
Iron/analysis*
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Minerals/chemistry*
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Drugs, Chinese Herbal/chemistry*
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X-Ray Diffraction
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Microscopy, Electron, Scanning
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Photoelectron Spectroscopy
3.Effects of acupuncture needle modification on acupuncture analgesia.
Ming-Zhu SUN ; Xin WANG ; Ying-Chen LI ; Yu-Hang LIU ; Yi YU ; Liu-Jie REN ; Wei GU ; Wei YAO
Journal of Integrative Medicine 2025;23(1):66-78
OBJECTIVE:
The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.
METHODS:
Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.
RESULTS:
The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.
CONCLUSION
Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles
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Acupuncture Analgesia/methods*
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Animals
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Rats
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Male
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Acupuncture Points
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Rats, Sprague-Dawley
4.Correlation between the level of NT-proBNP and cardiorespiratory fitness of individuals following acute high altitude exposure
Ping-Ping LI ; Xiao-Wei YE ; Jie YANG ; Zhe-Xue QIN ; Shi-Zhu BIAN ; Ji-Hang ZHANG ; Xu-Bin GAO ; Meng-Jia SUN ; Zhen LIU ; Hai-Lin LYU ; Qian-Yu JIA ; Yuan-Qi YANG ; Bing-Jie YANG ; Lan HUANG
Medical Journal of Chinese People's Liberation Army 2024;49(9):998-1003
Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.
5.Clinical application status of multiple localization methods in the treatment of pulmonary nodules by sub-lobectomy
Dingpei HAN ; Su YANG ; Xiang CHEN ; Wei, GUO ; Jie XIANG ; Lianggang ZHU ; Jiaming CHE ; Junbiao HANG ; Hecheng LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):160-165
The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.
6.Three-dimensional Printing of Inertial Microchannel with Complex Cross-section and Characterization of Particle Inertial Focusing
Qiao GU ; Xin-Jie ZHANG ; Yao LIU ; Yang BAO ; Hang-Jie ZHU ; Ya-Wei CHEN
Chinese Journal of Analytical Chemistry 2024;52(1):93-101
Projection micro stereolithography three-dimensional(3D)printing method was proposed in this study to fabricate complex microchannels of combined cross-sections.By using 3D printing and polydimethylsiloxane(PDMS)replication methods,two inertial microfluidic chips of three-step and five-step cross-sections were fabricated,and the dimension precisions of the microchannels were controlled within 20 μm.Using the microfluidic chips,the movements of two fluorescent polystyrene particles with diameters of 10 and 6 μm in the stepped channels were investigated.In addition,numerical simulations were applied to demonstrate the inertial focusing mechanisms of particles in the channels.It was found that 10-μm particles had three equilibrium positions in the three-step channel,which located at the inner walls of the three steps,respectively,and most particles focused at the inner step.The 6-μm particles also had three equilibrium positions in the three-step channel.However,the particles migrated to the middle and the outer steps under high flow rates.In the five-step channel,when the flow rate was increased gradually,10-μm particles had a single and two equilibrium positions,respectively,and the particles migrated towards the inner channel wall under high flow rates.In comparison to 10-μm particles,6-μm particles had two stable equilibrium positions in the five-step channel at all flow rate range.It could be concluded that the quantity,shape and strength of the secondary flow vortex could be altered by changing structure of the combined cross-section,thus the equilibrium positions and quantities of the focusing particles could be also regulated.The research outcome might provide new insights for precise cell inertial manipulation and promote the application and development of inertial microfluidic technology in biomedical and other fields.
7.An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023)
Jie SHEN ; Lin CHEN ; Shiwu DONG ; Jingshu FU ; Jianzhong GUAN ; Hongbo HE ; Chunli HOU ; Zhiyong HOU ; Gang LI ; Hang LI ; Fengxiang LIU ; Lei LIU ; Feng MA ; Tao NIE ; Chenghe QIN ; Jian SHI ; Hengsheng SHU ; Dong SUN ; Li SUN ; Guanglin WANG ; Xiaohua WANG ; Zhiqiang WANG ; Hongri WU ; Junchao XING ; Jianzhong XU ; Yongqing XU ; Dawei YANG ; Tengbo YU ; Zhi YUAN ; Wenming ZHANG ; Feng ZHAO ; Jiazhuang ZHENG ; Dapeng ZHOU ; Chen ZHU ; Yueliang ZHU ; Zhao XIE ; Xinbao WU ; Changqing ZHANG ; Peifu TANG ; Yingze ZHANG ; Fei LUO
Chinese Journal of Trauma 2023;39(2):107-120
Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.
8.Investigation of 2019-nCoV reinfection in previously infected people in Suzhou
Yuanyuan ZHANG ; Hui HANG ; Qian XU ; Cheng LIU ; Yayun TAN ; Pengwei CUI ; Lin BAO ; Hui LIU ; Shanshan LU ; Feng XU ; Yuanyuan PANG ; Ge TIAN ; Jun ZHANG ; Jie ZHU ; Liling CHEN
Chinese Journal of Epidemiology 2023;44(11):1756-1761
Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.
9.Effect of continuous renal replacement therapy on the control of different grades of intra-abdominal hypertension in patients with severe acute pancreatitis
Yi HANG ; Jun ZHU ; Ying YE ; Weichao DING ; Jie KANG
Chinese Journal of Emergency Medicine 2023;32(11):1501-1505
Objective:To analyze the effect and clinical significance of continuous renal replacement therapy (CRRT) on severe acute pancreatitis complicated with different grades of intra-abdominal hypertension, and to determine whether the level of intra-abdominal pressure can be used as one of the indicators of CRRT in these patients.Methods:From September 2020 to September 2022, the clinical data of 66 patients with severe acute pancreatitis complicated by intra-abdominal pressure (IAP) ≥12 mmHg who were treated with CRRT and admitted to the EICU of Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. According to the level of IAP, they were divided into group A: 12 mmHg≤IAP < 15 mmHg, 22 cases; group B: 15 mmHg≤IAP≤20 mmHg, 23 cases and group C: IA P>20 mmHg, 21 cases. The general clinical data and IAP values before and after CRRT treatment, as well as the ΔIAP (difference of IAP before and after treatment) were recorded. The difference of IAP before and after treatment and the ΔIAP between group B and group C were compared by independent sample t test. The relationship between IAP before treatment and ?IAP was analyzed by spearman test. Results:There were no significant differences in gender, age, modified Marshall score, APACHE Ⅱ score, number of mechanical ventilation, and etiology among the three groups before treatment( P>0.05). After CRRT treatment, IAP of group A was no significantly changed before and after treatment ( P>0.05). IAP in groups B and C was significantly lower after treatment than before treatment ( P<0.05), and the ΔIAP of group C was significantly higher than that of group B ( P<0.05). There was a positive correlation between IAP before treatment and ?IAP in group B and Group C ( P<0.05). Conclusions:1.For patients with severe pancreatitis complicated with intra-abdominal hypertension, CRRT treatment can effectively reduce IAP when IAP≥15 mmHg, and the higher the IAP, the more obvious effect of CRRT treatment in controlling intra-abdominal pressure. 2. IAP≥15 mmHg can be used as one of the indicators for CRRT in SAP patients.
10.Clinical value of combined detection of chromosomal karyotype and Y chromosome microdeletion in azoospermia or oligo-spermia
Jiankun ZHOU ; Yi YAN ; Hang ZHONG ; Jie DENG ; Xidan ZHU ; Qing LUO
Chinese Journal of Clinical Laboratory Science 2023;41(10):745-748
Objective To analyze and diagnose the chromosomal genetic etiology of male patients with azoospermia or oligozoospermia,and investigate the clinical application value of combined detection of chromosomal karyotype and Y-chromosome microdeletion in azoospermia or oligozoospermia.Methods The clinical data and peripheral blood samples of 240 male patients with azoospermia or oli-gospermia in Luzhou district of Sichuan were collected.The karyotype analysis of peripheral blood lymphocytes were analyzed by G-ban-ding in conventional chromosomal culture.Multiplex PCR technology was used to detect Y chromosome microdeletions.Results A-mong the 240 male patients with azoospermia or oligospermia,179 cases of azoospermia and 61 cases of severe oligospermia were found.The detection rate of chromosome karyotype abnormalities was 22.92%(55/240),including 30 cases of chromosome number abnor-malities,21 chromosome structure abnormalities and 4 combined abnormalities.The detection rate of Y chromosome microdeletion ab-normalities was 10.42%(25/240)with the highest deletion rate of 7.08%for AZFc abnormalities.The combined detection rate for the abnormalities of karyotype and Y chromosome microdeletion was 30.83%(74/240),among which 6 patients showed abnormalities in both detections.The detection rate of combined detections by the two methods was higher than that of single method(x2=30.24,P<0.001).Conclusion This study systematically reported the incidence and types of karyotypes and Y chromosome microdeletions in male azoospermia or oligospermia patients in Luzhou district of Sichuan.We suggest that the combined application of the two methods may improve the detection rate of abnormality,which provides important guidance for the etiological diagnosis of male infertility pa-tients,genetic counseling and reproductive therapy.

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