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.Research progress in regulatory mechanism and traditional Chinese medicine intervention of circular RNA for coronary atherosclerotic heart disease
Lan-Tian HU ; Xue-Na XIE ; Yu-Ying WANG ; Mei LIU ; Hong-Ai GUO ; Rong YUAN ; Qi-Qi XIN ; Yu MIAO ; Wei-Hong CONG
Chinese Pharmacological Bulletin 2024;40(11):2014-2019
Coronary atherosclerotic heart disease(CHD)is an ischemic cardiovascular condition caused by the narrowing or blockage of the vascular lumen due to coronary atherosclerosis.Clinically,it presents as angina pectoris,heart failure,or sud-den cardiac death,and stands as one of the primary causes of mortality among both urban and rural populations in China.Cir-cRNA,classified as non-coding RNAs,can function as upstream regulatory molecules for miRNA or RNA-binding proteins.They actively participate in various pathological processes associated with CHD,including endothelial cell dysfunction,smooth mus-cle cell migration,macrophage-derived foam cell formation,an-giogenesis,myocardial injury,and repair,as well as post-in-farction heart failure.The expression pattern of these molecules is highly specific to the illness and tissue,indicating their poten-tial as therapeutic targets for disease management and as biomar-kers.Furthermore,they also open up new avenues for drug tar-get development in the field of traditional Chinese medicine.This article aims to provide an overview of the recent research progress on circRNA in the regulation of coronary heart disease,as well as the mechanisms involved in traditional Chinese medi-cine.It serves as a valuable reference for future research on cor-onary heart disease.
3.Development and reliability and validity test of the Psychological Birth Trauma Assessment Scale
Xiaoqing SUN ; Aixia ZHANG ; Zhu ZHU ; Xuemei FAN ; Shijuan MEI ; Xinxin HUANG ; Shengnan CONG ; Hongyan XIE
Chinese Journal of Nursing 2024;59(9):1099-1105
Objective To develop a Psychological Birth Trauma Assessment Scale and to test its reliability and validity.Methods Through literature review,semi-structured interview,expert conference,Delphi expert enquiry and preliminary investigation,a pre-test scale was formed.From March to May 2023,postpartum women from 38 hospitals of different levels in 15 provinces(Jiangsu,Anhui,Zhejiang,Fujian,Tibet,and Shanghai,etc.)were conveniently selected for investigation.The sample size of the first-round survey was 547,which was used for reliability and validity test.The sample size of the second-round survey was 550,which was used for confirmatory factor analysis.Results The psychological birth trauma assessment scale consisted of 2 parts,with a total of 29 items in 6 dimensions.The intrapartum feeling part included 4 dimensions,with a cumulative variance contribution rate of 63.992%,and the postpartum effect part included 2 dimensions,with a cumulative variance contribution rate of 68.208%.The content validity index of the scale was 0.947,and the content validity index of each item was 0.809~1.000.The total score of the scale and the scores of each dimension were significantly negatively correlated with the total score of the calibration scale(r=-0.784~-0.533,P<0.001).The total Cronbach's α coefficient was 0.941,and the split-half reliability coefficient was 0.883.Confirmatory factor analysis showed that the main evaluation indicators were all within the acceptable range.Conclusion The Psychological Birth Trauma Assessment Scale has good reliability and validity,and it can be used as an assessment tool for the degree of maternal psychological birth trauma.
4.Application of a New Type Non-inflatable Retractor in Transoral Endoscopic Thyroidectomy via Submental and Vestibular Approach
Zhiqiang JIANG ; Mengqiao DAI ; Zihang AI ; Huilin LUO ; Cong LIAO ; Yang XIE ; Yong YING ; Xiangtai ZENG
Chinese Journal of Minimally Invasive Surgery 2024;24(8):534-539
Objective To investigate the safety of using a self-made new type non-inflatable retractor for transoral endoscopic thyroidectomy via submental and vestibular approach(TOETSMVA).Methods A retrospective analysis was conducted on the surgical records of 119 cases of unilateral thyroid lobe tumor from January 2021 to June 2022.Among them,37 cases underwent non-inflatable TOETSMVA by using a new type non-inflatable retractor(non-inflatable group),37 cases underwent traditional inflatable TOETSMVA(inflatable group),and 45 cases underwent traditional open anterior cervical thyroid surgery(open group).The differences in surgical indicators,postoperative complications,and patient satisfaction with incision were compared among the three groups.Results Compared with the open group,the non-inflatable group had longer operation time[(131.0±20.1)min vs.(81.1±15.7)min,P=0.000],but less intraoperative blood loss[19(15,27)ml vs.30(25,37)ml,P=0.000],lower pain score on the first day after surgery[(4.8±2.1)points vs.(6.4±1.9)points,P=0.000],and higher patient's satisfaction with the incision(the number of cases of very dissatisfied,dissatisfied,satisfied,comparatively satisfied,and very satisfied were 0,0,6,16,15 vs.4,3,19,17,2,P=0.000).Compared with the inflatable group,the non-inflatable group had shorter surgical time[(131.0±20.1)min vs.(141.8±22.9)min,P=0.019],and there were no statistically significant differences in intraoperative bleeding volume,pain score on the first day after surgery,and patient satisfaction with the incision(P>0.05).There were no statistically significant differences in the number of lymph node dissection,total postoperative drainage volume,and parathyroid hormone(PTH)levels on the first day after surgery among the three groups(P>0.05).Postoperative bleeding occurred in 1 case in the open group,and 1 case of hoarseness and 1 case of subcutaneous ecchymosis of the neck were noted in the non-inflatable group.No tracheoesophageal injury,severe subcutaneous emphysema,hypercapnia,or gas embolism happened among the three groups.Conclusions The new type non-inflatable retractor can effectively maintain space during TOETSMVA surgery.Compared with traditional open anterior cervical thyroid surgery and conventional inflatable TOETSMVA,it has better surgical safety.
5.The value of pulmonary high-frequency ultrasound score combined with serum IL-6, CRP and PCT levels in evaluating the prognosis of neonatal respiratory distress syndrome
Yang GAO ; Cong LI ; Yanhui RU ; Hong YIN ; Yuan XIE ; Yuehua GAO
Journal of Chinese Physician 2024;26(5):717-721
Objective:To explore the value of high frequency ultrasound scoring combined with serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in evaluating the prognosis of neonatal respiratory distress syndrome (NRDS) in children.Methods:A total of 106 children with NRDS who were treated at Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University from March 2021 to December 2022 were selected. According to the discharge outcome, NRDS patients were divided into a poor prognosis group ( n=11) and a good prognosis group ( n=95), and the clinical data differences between the two groups were compared. At the same time, NRDS patients were divided into mild to moderate group ( n=75) and severe group ( n=31) based on the severity of the disease. The differences in high-frequency ultrasound scores of the lungs and serum levels of IL-6, CRP, and PCT were analyzed in children with different disease severity levels of NRDS. Logistic multiple regression analysis was used to identify the influencing factors of prognosis; receiver operating characteristic (ROC) curve analysis of lung high-frequency ultrasound score, IL-6, and their combination predicted the prognostic value of NRDS in children. Results:The gestational age, birth weight, and high-frequency ultrasound scores of the lungs in the poor prognosis group were significantly lower than those in the good prognosis group (all P<0.05); The proportion of diabetes in pregnancy, the proportion of severe disease, the first use time of pulmonary surfactant (PS) and the level of IL-6 in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). The serum levels of IL-6, CRP, and PCT in severe children were significantly higher than those in mild to moderate children (all P<0.05); The high-frequency ultrasound score of the lungs in severe children was significantly lower than that in mild to moderate children ( P<0.05). Logistic regression analysis showed that gestational age, pulmonary high-frequency ultrasound score, gestational diabetes, disease severity, and IL-6 were the influencing factors for poor prognosis of children with NRDS (all P<0.05). The area under the ROC curve for predicting poor prognosis in children with NRDS using high-frequency ultrasound score, IL-6, and their combination were 0.745, 0.802, and 0.786, respectively. Conclusions:The severity of NRDS in children is related to the high-frequency ultrasound score of the lungs and serum levels of IL-6, CRP, and PCT. At the same time, the high-frequency ultrasound score of the lungs and IL-6 are related to the prognosis of NRDS children, and have certain application value in predicting the prognosis of children.
6.Preliminary application of three-dimensional ultrasound fusion imaging visualization technology guiding precise needle placement for thermal ablation of hepatocellular carcinoma
Yueting SUN ; Yuqing GUO ; Jiaming LIU ; Ming LIU ; Longfei CONG ; Baoxian LIU ; Xiaoyan XIE ; Guangliang HUANG
Chinese Journal of Ultrasonography 2024;33(2):158-164
Objective:To preliminarily explore the clinical value of three-dimensional ultrasound fusion imaging(3DUS FI) visualization technology in guiding precise needle placement during thermal ablation of hepatocellular carcinoma (HCC).Methods:A total of 56 HCC patients (59 lesions)who underwent 3DUS FI guided thermal ablation were retrospectively analyzed in the First Affiliated Hospital of Sun Yat-sen University from November 2019 to December 2021. All patients were collected with three-dimensional ultrasound volume image before ablation which were fused with real-time two-dimensional ultrasound image for registration, and then the tumor and the safety margin of 5 mm were segmented and marked. Finally, the thermal ablation was performed under three-dimensional visualization. Contrast-enhanced CT/MRI was performed 1 month after thermal ablation to evaluate whether the lesion was completely ablated and measure the ablative margin, and the relationship between ablative margin and the incidence of local tumor progression (LTP) was also analyzed.Results:During the ablation, all lesions could be successfully registered and displayed in three-dimension. Postoperative contrast-enhanced ultrasound showed that all lesions were completely ablated. A total of 37 lesions could be evaluated for ablative efficacy and ablative margin based on contrast-enhanced CT/MRI 1 month after themal ablation, of which 32 (86.5%) lesions achieved complete ablation and obtained at least 5 mm ablative margin. During the follow-up period, LTP was occurred in 4 lesions, 3 of the lesions occurred at the ablative margin< 5 mm. Both 1-year and 2-year cumulative LTP rates were all 7.1%. None of patients had serious complications or deaths associated with thermal ablation.Conclusions:3DUS FI real-time guidance technology is feasible and safe in visually guiding precise needle placement during thermal ablation of HCC.
7.Preoperative planning of Cam-type femoroacetabular impingement using spherical fitting technique in CT three-dimensional reconstruction
Chun ZENG ; Shuang CONG ; Denghui XIE ; Jianying PAN ; Guangxin HUANG
Chinese Journal of Orthopaedics 2024;44(2):70-78
Objective:To explore the feasibility and effect of applying spherical fitting technology in CT three-dimensional reconstruction in preoperative planning of the resection range of Cam-type femoral acetabular impingement (FAI).Methods:46 Cam-type FAI patients who underwent arthroscopic femoroplasty in the Department of Sports Medicine in the Third Affiliated Hospital of Southern Medical University from July 2020 to June 2022 were enrolled in the spherical fitting group, including 26 females and 20 males, with an average age of 38.4±15.2 years (range of 24-53 years). The preoperative planning was performed using spherical fitting technology in CT three-dimensional reconstruction. Another 42 Cam-type FAI patients who underwent arthroscopic femoroplasty from July 2018 to June 2020 were enrolled in the observation group, including 25 females and 17 males, with an average age of 43.6±18.4 years (range 24-61 years). The preoperative planning was performed using CT three-dimensional reconstruction observation method. This study evaluated the impact of femoroplasty planned by spherical fitting technique on patients' prognosis though comparing the differences of postoperative α angle, femoral head-neck offset ratio, modified Harris hip score (mHHS), and visual analog score (VAS) at 3, 6, 9, and 12 months between two groups.Results:The average follow-up time was 11.8±0.6 months in spherical fitting group and 11.3±0.8 months in observation group. There was no significant difference regarding α angle, femoral head-neck offset ratio, mHHS, and VAS between two groups preoperatively ( P>0.05). The mHHS in two groups increased gradually, while VAS decreased sequentially at 3, 6, 9, and 12 months postoperatively. The postoperative mHHS and VAS were significantly better than those before surgery ( P<0.05). The mHHS was 83.2±14.8 vs. 70.5±11.2 in spherical fitting group and observation group at the followup of 9 months with significant difference ( t=4.471, P=0.007). It was 85.7±13.3 vs. 73.2±12.5 at the followup of 12 months with significant difference ( t=4.596, P=0.008). No significant difference was found in α angle, femoral head-neck offset ratio or mHHS at 3 and 6 months postoperatively ( P>0.05), and no significant difference was found in VAS at 3, 6, 9, and 12 months postoperatively between two groups. Conclusion:The spherical fitting technology in CT three-dimensional reconstruction could assist surgeons with planning of the resection range of Cam deformity preoperatively, and achieve a smooth progress of arthroscopic femoroplasty intraoperatively; after short term follow-up, we found that patients who underwent femoroplasty using this technology achieved satisfactory outcomes.
8.Clinical trial of ursodeoxycholic acid capsule in the treatment of patients with intrahepatic and extrahepatic bile duct stones
Xiang LI ; Cong XIE ; Bai-Hao ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2320-2324
Objective To observe the clinical effect of ursodeoxycholic acid capsules combined with laparoscopic-assisted choledochoscopic lithotomy in the treatment of intrahepatic and extrahepatic bile duct stones.Methods Patients with intrahepatic and extrahepatic bile duct stones were divided into the control group and the treatment group.The control group was treated with laparoscopic-assisted choledochoscopic lithotomy,and was given general maintenance treatment after operation,such as anti infection,liver protection,and nutritional support.On this basis,the treatment group was treated with ursodeoxycholic acid capsules(0.25 g,tid,orally administration,for 6 months).The symptom disappearance rate,liver function indicators[glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),total bilirubin(TBIL)],lipid metabolism indicators[total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)]and stone recurrence rate were compared between the two groups.The incidence rates of postoperative complications were calculated.Results Forty-five cases were included in the treatment group and forty-three cases in the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.56%(43 cases/45 cases)and 81.40%(35 cases/43 cases)(P<0.05).Six months after surgery,the disappearance rates of upper abdominal pain in the treatment group and the control group were 95.56%(43 cases/45 cases)and 81.40%(35 cases/43 cases);the disappearance rates of hepatic tenderness were 100.00%(45 cases/45 cases)and 86.05%(37 cases/43 cases);GPT levels were(31.54±6.27)and(38.29±6.63)U·L-1;GOT levels were(38.75±5.52)and(43.46±5.08)U·L-1;total bilirubin(TBIL)levels were(26.57±6.39)and(32.28±7.61)μmol·L-1;total cholesterol(TC)levels were(5.29±1.06)and(6.12±1.03)mmol·L-1;triglyceride(TG)levels were(1.45±0.43)and(1.69±0.46)mmol·L-1;high density lipoprotein(HDL)levels were(1.69±0.36)and(1.51±0.39)mmol·L-1;stone recurrence rates were 0(0 cases/45 cases)and 11.63%(5 cases/43 cases).The differences between groups were statistically significant(all P<0.05).The main adverse drug reactions in the treatment group were nausea and diarrhea,while there were no adverse drug reactions in the control group.The total incidence of adverse drug reactions in the treatment group and control group were 6.67%(3 cases/45 cases)and 0(0 cases/43 cases),with no statistically significant difference(P>0.05).Conclusion The application of ursodeoxycholic acid capsules after laparoscopic-assisted choledochoscopic lithotomy can promote the improvement of clinical symptoms and liver function in patients with intrahepatic and extrahepatic bile duct stones,accelerate lipid metabolism,and prevent stone recurrence.
9.Study on Evidence-Based Decision-Making of Acupuncture for Post-Prostatectomy Urinary Incontinence: based on TOPSIS Combined with Entropy Method
Zhiwei DONG ; Junlan WANG ; Tao XIE ; Yanying YE ; Ting LI ; Cong YU ; Ning TIAN
Journal of Traditional Chinese Medicine 2024;65(23):2434-2441
ObjectiveTo screen optimized protocol of acupuncture for post-prostatectomy urinary incontinence (PPUI) patients, and to provide evidence for clinical practice. MethodsMEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, WanFang and VIP databases were searched to collect randomized controlled trials of acupuncture for PPUI. The search was conducted from the establishment of the database to February 1, 2024, and the quality of the literature was evaluated to exclude the studies with a high risk of overall bias or modified Jadad <3, and constructed acupuncture protocol and performed meta-analysis. We used International Consultation on Urinary Incontinence Short Form (ICI-Q-SF) scores, quality of life scores, overall effective rate, and modified Jadad scores as beneficial indicators, and the number of acupoints selected, stimulation duration, the number of acupuncture, and the duration of the treatment course as costly indicators, to derive the standardized protocol matrix, and used the entropy method to determine the weights of the different decision-making indicators, and finally combined with the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation. ResultsNine studies met the criteria, and the acupuncture treatments involved were constructed as six protocols including electrical acupoint stimulation with low-frequency, electroacupuncture at four acupoints of sacral region, replenishing qi and tonifying kidney acupuncture, body acupuncture plus pelvic floor muscle training, auricular acupuncture, and electroacupuncture plus pelvic floor muscle training. The ICI-Q-SF, number of acupuncture sessions, and total effectiveness rate were given higher weights in the decision-making indexes, while the stimulation duration and the duration of treatment course were given lower weights; the entropy method of TOPSIS was used for the evaluation and proved that the best protocol was the electroacupuncture at four acupoints of sacral region which used continuous-wave electroacupuncture with a frequency of 2 Hz for 60 min each time, and required the needle sensation to radiate to the root of the penis, with the advantages of streamlined selection of acupoints, a significant reduction in ICI-Q-SF, and an increase in the effectiveness rate. ConclusionThe final optimized protocol was electroacupuncture at four acupoints of sacral region, which can provide an evidence-based basis for clinical decision-making and guideline development.
10.Construction and characterization of lpxC deletion strain based on CRISPR/Cas9 in Acinetobacter baumannii
Zong-ti SUN ; You-wen ZHANG ; Hai-bin LI ; Xiu-kun WANG ; Jie YU ; Jin-ru XIE ; Peng-bo PANG ; Xin-xin HU ; Tong-ying NIE ; Xi LU ; Jing PANG ; Lei HOU ; Xin-yi YANG ; Cong-ran LI ; Lang SUN ; Xue-fu YOU
Acta Pharmaceutica Sinica 2024;59(5):1286-1294
Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria,

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