1.Clinical efficacy of minimally invasive tendon blade technique in the treatment of moderate and severe gluteal muscle contracture.
Jia-Kai GAO ; Tao-Ran WANG ; Long BI ; Xiao-Chao CHEN ; Yan-Wu LIU ; Yao-Ping WU ; Xiang HE ; Zhi-Xia NIU
China Journal of Orthopaedics and Traumatology 2025;38(4):420-423
OBJECTIVE:
To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture.
METHODS:
A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated.
RESULTS:
The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks.
CONCLUSION
Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans
;
Male
;
Female
;
Adult
;
Minimally Invasive Surgical Procedures/methods*
;
Adolescent
;
Retrospective Studies
;
Buttocks/surgery*
;
Young Adult
;
Contracture/surgery*
;
Tendons/surgery*
;
Muscle, Skeletal/surgery*
2.Clinical features and immunotherapy for children with loss-of-function/gain-of-function mutations in the STAT gene: an analysis of 10 cases.
Hong-Wei LI ; Yan-Hong WANG ; Shang-Zhi WU ; Bi-Yun ZHANG ; Shi-Hui XU ; Jia-Xing XU ; Zhan-Hang HUANG ; Cheng-Yu LU ; De-Hui CHEN
Chinese Journal of Contemporary Pediatrics 2025;27(8):951-958
OBJECTIVES:
To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies.
METHODS:
A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment.
RESULTS:
For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms.
CONCLUSIONS
STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans
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Male
;
Immunotherapy
;
Female
;
Child, Preschool
;
Child
;
Gain of Function Mutation
;
Retrospective Studies
;
Infant
;
Loss of Function Mutation
;
STAT Transcription Factors/genetics*
3.Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats
Si-ju LI ; Qian ZHANG ; Yun LENG ; Bi-yan PAN ; Zhi-yong XIE ; Hong-ying CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):232-243
ObjectiveUsing multi-omics technology, we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups (n = 6 each): Control group, Model group and Dexamethasone (Dex) group. Lipopolysaccharide (LPS) was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days, and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day, lung, plasma, feces and intestinal contents of rat were collected. Hematoxylin-eosin (H&E) staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore, metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats, respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells, the alveolar septum was increased, alveolar hemorrhage, and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α (P < 0.000 1), IL-1α (P = 0.009 6) and IL-6 (P < 0.000 1) in the Model group were increased compared with the Control group, while Dex treatment reduced the levels of the three inflammatory factors. Taken together, Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group, an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium, Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group, indicating metabolic profile changes. In addition, 69 metabolites (P < 0.05) were screened, including 38 up-regulated in the Model group and 31 elevated in the Dex group, all of which were mainly involved in 3 metabolic pathways: linoleic acid metabolism, tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary, we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile, integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.
4.Study on the mechanism of metformin promoting brain protection via AMPK autophagy signal pathway
Zhi-Fang QIN ; Yan-Ze WANG ; Bi-Hua CHEN ; Man-Hong ZHOU
The Chinese Journal of Clinical Pharmacology 2023;39(23):3424-3428
Objective To explore whether metformin preconditioning can protect brain injury after cardiac arrest/cardiopulmonary resuscitation(CA/CPR)and its possible mechanisms and signaling pathways.Methods Constructed a CA model by using electrical stimulation.Rats were randomly divided into the sham group(0.9%NaCl gavage daily for 14 days,without inducing CA),model group(CA model was induced after 0.9%NaCl gavage daily for 14 days),experimental group(CA model was induced after 200 mg·kg-1 Met+0.9%NaCl gavage daily for 14 days),Cc group[200 mg·kg-1 Met+0.9%NaCl gavage daily for 14 days,adenosine 5'-monophosphate kinase-activated protein(AMPK)inhibitor Compoud C(Cc)was injected intraperitoneally at 1 hour before modeling],chloroquine(CQ)group(daily 200 mg·kg-1 Met+0.9%NaCl gavage for 14 days,intraperitoneal injection of autophagy inhibitor CQ at 1 hour before modeling)and AICAR group(continuous daily 200 mg·kg-1 Met+0.9%NaCl gavage for 14 days,intraperitoneal injection of AMPK agonist AICAR at 1 hour before modeling).The 7-day survival rate after CA/CPR via using survival curves was recorded;the neurological function 7-days after CA/CPR was scored by using the neurological disability scale;the protein malondialdehyde(MDA)level were measured using the Coomassie Brilliant Blue method;detection of reactive oxygen species(ROS)levels in brain tissue by using ROS fluorescent probe DHE;Western blotting was used to determine the expression levels of related proteins such as AMPK,p-AMPK,microtubule associated protein 1 light chain 3 Ⅰ(LC3 Ⅰ),LC3 Ⅱ,and p62 in brain tissue.Results The 7-day survival rates of sham,model,experimental,Cc,CQ and AICAR groups rats were 100%,40%,70%,40%,40%and 65%,respectively;the 7-day neurological function scores were 78.35±1.65,46.50±4.41,67.93±4.64,49.50±3.53,52.00±2.83 and 68.33±1.53,respectively;the ROS levels were(417.60±8.37),(748.60±36.05),(575.80±10.73),(713.80±18.85),(668.20±9.58)and(566.00±24.48)U·mg-1,respectively;the MDA levels were(4.38±0.33),(8.06±0.76),(5.50±0.48),(7.18±0.29),(6.82±0.31)and(5.20±0.34)nmol·mg-1,respectively;the brain tissue p-AMPK/AMPK were 0.74±0.04,0.87±0.01,1.61±0.01,0.55±0.05,1.09±0.09 and 1.27±0.07,respectively;the p62 values were 0.42±0.02,0.86±0.05,0.61±0.04,0.98±0.04 and 0.78±0.03,respectively;the LC3 Ⅱ/LC3 1 were 0.29±0.32,0.37±0.26,0.96±0.78,0.58±0.26,0.43±0.03 and 1.40±0.10,respectively.Compared with the model group,the differences of above indexes in the experimental group,AICAR group were statistically significant(all P<0.05);compared with the experimental group,the differences of above indexes in the Cc group,CQ group were statistically significant(all P<0.05).Conclusion Metformin preconditioning can play a protective role in brain injury after cardiac arrest/cardiopulmonary resuscitationin in rats by activating the AMPK signaling pathway,regulating mitochondrial energy metabolism and promoting autophagy.
5.Functional dyspepsia treated with acupuncture of different frequencies: a randomized controlled trial.
Kai-Yuan TANG ; Bi-Yun SUN ; Yan YAN ; Xi WANG ; Xin HE ; Zhi-Shun LIU
Chinese Acupuncture & Moxibustion 2023;43(6):622-626
OBJECTIVE:
To compare the clinical efficacy of acupuncture with different frequencies in the treatment of patients with functional dyspepsia (FD).
METHODS:
A total of 90 patients with FD were randomly divided into a 3-time acupuncture treatment per week group (3-A group, 31 cases, 2 cases dropped off), a 1-time acupuncture treatment per week group (1-A group, 30 cases, 2 cases dropped off) and a control group (29 cases, 2 cases dropped off). In the two acupuncture groups, the acupoints were Zhongwan (CV 12) and bilateral Tianshu (ST 25), Neiguan (PC 6), Liangqiu (ST 34), Yanglingquan (GB 34), Zusanli (ST 36) and Taichong (LR 3), stimulated 3 times a week and once a week, respectively; and the treatment was given consecutively for 4 weeks. In the control group, no intervention was adopted, but the compensatory therapy was provided after the end of follow-up. The scores of the symptom index of dyspepsia (SID), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were compared among the 3 groups before treatment, after 4 weeks of treatment and in 4 and 8 weeks after treatment completion separately. The score of Nepean dyspepsia life quality index (NDLQI) was evaluated before treatment, after 2 and 4 weeks of treatment and in 4 and 8 weeks after treatment completion.
RESULTS:
After 4 weeks of treatment and in 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS were all reduced in the 3-A group and the 1-A group when compared with the scores before treatment (P<0.000 1, P<0.05). After 4 weeks of treatment, the scores of SID, SAS and SDS in the two acupuncture groups were lower than those in the control group (P<0.000 1). After 2 and 4 weeks of treatment, the increased values of NDLQI score in the two acupuncture groups were all higher than those in the control group (P<0.05). In 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS in the 3-A group were lower than those in the 1-A group (P<0.001, P<0.05), and the increased values of NDLQI score in the 3-A group were higher than those in the 1-A group (P<0.000 1).
CONCLUSION
Acupuncture given 3 times per week is superior to the treatment given once per week in the aspects of relieving the clinical symptoms, improving the quality of life and regulating the emotional state in patients with FD. This efficacy is persistent for 8 weeks after treatment completion.
Humans
;
Dyspepsia/therapy*
;
Quality of Life
;
Acupuncture Therapy
;
Acupuncture Points
;
Emotions
6.Value of contrast-enhanced percutaneous ultrasound in the diagnosis of rotator cuff tear subtype.
Bi-Li LIU ; Yue SHAN ; Qi ZHONG ; Dan GE ; Yan-Ping LI ; Juan LYU ; Shu-Zhi GAN
China Journal of Orthopaedics and Traumatology 2023;36(10):974-981
OBJECTIVE:
To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes.
METHODS:
From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated.
RESULTS:
The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears).
CONCLUSION
Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.
Male
;
Female
;
Humans
;
Infant, Newborn
;
Infant
;
Child, Preschool
;
Child
;
Rotator Cuff Injuries/diagnostic imaging*
;
Rotator Cuff/diagnostic imaging*
;
Sensitivity and Specificity
;
Ultrasonography
;
Magnetic Resonance Imaging/methods*
;
Rupture
;
Arthroscopy
7.Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity.
Can-Chao JIA ; Ling-Jie LI ; Zhi-Hao ZENG ; Rui-Yin TANG ; De-Zheng JIA ; Min-Juan YANG ; Jin-Yan QIU ; Dong-Mei LI ; Can-Hui XIE ; Guang-Ying WU ; Yang-Xue LI ; Jie-Yi JIANG ; Hong HUANG ; Guan-Lin XIAO ; Da-Ke CAI ; Xiao-Li BI
China Journal of Chinese Materia Medica 2023;48(16):4421-4428
This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans
;
Chromatography, High Pressure Liquid
;
Drugs, Chinese Herbal/chemistry*
;
Asteraceae/chemistry*
;
Lung Neoplasms/drug therapy*
8.Effect and Mechanism of miR-4321 Inhibition Alleviates Sepsis Associated Acute Kidney Injury
Chun-min ZHANG ; Fei-yan CHEN ; Wen-min YANG ; Yong-min LIN ; Bi-tao MAO ; Jie CHEN ; Zhi-yuan WU ; Yu-feng LIANG
Journal of Sun Yat-sen University(Medical Sciences) 2022;43(6):928-937
ObjectiveSepsis associated acute kidney injury (SA-AKI) is a critical clinical disease. The purpose of this study was to investigate the role and molecular mechanism of miR-4321 in the HK2 cellular damage induced by lipopolysaccharides (LPS). MethodsRT-qPCR was conducted to detect the expression of miR-3165, miR-4270 and miR-4321 in LPS-induced HK2 cell model and cecal ligation and puncture (CLP)-induced renal injury model. In LPS-induced HK2 cell model, miR-4321-inhibitor was used to inhibit the miR-4321 expression. The effects of miR-4321 on cell proliferation, cell viability, cytokines and apoptosis-related protein levels were evaluated by CCK-8 analysis, EdU staining analysis and western blotting analysis, respectively. In CLP-induced renal injury model, miR-4321-Antago was used to intervene the miR-4321 expression. The changes of renal tissue structure were examined by H&E staining. The levels of serum creatinine and blood urea nitrogen (BUN) were measured by colorimetric method. ELISA was employed to assess the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum. IHC staining and western blotting were performed to determine the mTOR level and apoptosis-related protein expression in kidney tissues. Target genes of miR-4321 were predicted by Targetscan software and verified by dual-luciferase reporter assay. ResultsCompared with the control group, the miR-4321 expression was increased in LPS-induced HK2 cell model (n=3, t=7.154, P=0.001 3). miR-4321 inhibitor promoted the proliferation and viability of HK2 cells, decreased the expression of LPS-induced IL-6, IL-1β and TNF-α and apoptosis-related proteins. In vivo experiments showed that miR-4321-Antago inhibited serum creatinine and BUN levels in CLP mice, improved renal injury, reduced levels of IL-1β, IL-6 and TNF-α, promoted the mTOR expression in renal tissues and inhibited the apoptosis-related protein expression. mTOR signaling pathway was believed the target gene of miR-4321. ConclusionInhibition of miR-4321 significantly alleviates SA-AKI, which may be achieved by increasing the expression of mTOR.
9.Efficacy and Safety of the Safe Triangular Working Zone Approach in Percutaneous Vertebroplasty for Spinal Metastasis
Bi Cong YAN ; Yan Feng FAN ; Qing Hua TIAN ; Tao WANG ; Zhi Long HUANG ; Hong Mei SONG ; Ying LI ; Lei JIAO ; Chun Gen WU
Korean Journal of Radiology 2022;23(9):901-910
Objective:
This study aimed to assess the technical feasibility, efficacy, and safety of the safe triangular working zone (STWZ) approach applied in percutaneous vertebroplasty (PV) for spinal metastases involving the posterior part of the vertebral body.
Materials and Methods:
We prospectively enrolled 87 patients who underwent PV for spinal metastasis involving the posterior part of the vertebral body, with or without the STWZ approach, from January 2019 to April 2022. Forty-nine patients (27 females and 22 males; mean age ± standard deviation [SD], 57.2 ± 11.6 years; age range, 31–76 years) were included in group A (with STWZ approach), accounting for 54 vertebrae. Thirty-eight patients (18 females and 20 males; 59.1 ± 10.9 years; 29–81 years) were included in group B (without STWZ approach), accounting for 57 vertebrae. Patient demographics, procedure-related variables, and pain relief as assessed using the visual analog scale (VAS) were collected at different time points. Tumor recurrence in the vertebrae after PV was analyzed using Kaplan–Meier curves.
Results:
The STWZ approach was successful from T1 to L5 without severe complications. Cement filling was satisfactory in 47/54 (87.0%) and 25/57 (43.9%) vertebrae in groups A and B, respectively (v< 0.001). Cement leakage was not significantly different between groups A and B (p= 1.000). Mean VAS score ± SD before and 1 week and 1, 3, 6, 9, and 12 months after PV were 7.6 ± 1.8, 4.2 ± 2.0, 2.7 ± 1.9, 1.9 ± 1.5, 1.7 ± 1.4, 1.7 ± 1.1, and 1.6 ± 1.3, respectively, in group A and 7.2 ± 1.7, 4.0 ± 1.3, 3.4 ± 1.6, 2.4 ± 1.2, 1.8 ± 1.0, 1.4 ± 0.5, and 1.7 ± 0.9, respectively, in group B. Kaplan–Meier analysis showed a lower tumor recurrence rate in group A than in group B (p = 0.001).
Conclusion
The STWZ approach may represent a new, safe, alternative/auxiliary approach to target the posterior part of the vertebral body in the PV for spinal metastases.
10.Mechanism of Fangji Fulingtang for Treating Acute Kidney Injury Induced by Ischemia-reperfusion Based on Network Pharmacology and Molecular Docking Verification
Jun-xin HUANG ; Bi-xia WANG ; Han-bin ZOU ; Qiu-xin WU ; Xin YIN ; Shu-ying HUANG ; Jun-bin XIE ; Qing-qi YANG ; Zhi-yan GAO ; Zheng-yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):175-182
ObjectiveTo explore the mechanism of Fangji Fulingtang in the treatment of acute kidney injury (AKI) induced by ischemia-reperfusion based on network pharmacology and experimental verification. MethodActive components of Fangji Fulingtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and previous report and targets of these components were predicted by SwissTargetPrediction. The targets of AKI were searched from GeneCards, Online Mendelian Inheritance in Man (OMIM), the database of gene-disease associations (DisGeNET), and Therapeutic Target Database (TTD). Protein-protein interaction (PPI) network was constructed by STRING. Metascape was used for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of core targets. Cytoscape was employed to construct the "medicinal-active component-target-disease" network and “active component-target-pathway” network. AutoDock was applied for molecular docking. Finally, animal experiment was carried out to validate the mechanism of Fangji Fulingtang in treatment of AKI. ResultA total of 137 active components and 858 targets of Fangji Fulingtang, 1 294 targets of AKI, and 267 targets of Fangji Fulingtang in the treatment of AKI were screened out. Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene tyrosine protein kinase (SRC), protein kinase B1 (Akt1), and mitogen-activated protein kinase 3 (MAPK3) were the key anti-AKI targets of Fangji Fulingtang, which were involved in 1 609 GO terms, particularly cell response to lipids, membrane rafts, and protein kinase activity, and 140 KEGG pathways such as PI3K/Akt signaling pathway, chemokine signaling pathway, and Toll-like receptor signaling pathway. Molecular docking showed that the core active components had strong binding affinity to the key targets. The hematoxylin and eosin (HE) staining results indicated that Fangji Fulingtang can significantly improve the pathological state and the serological results suggested that the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were significantly reduced. ConclusionThis study clarified the mechanism of Fangji Fulingtang in the treatment of AKI and found that Fangji Fulingtang had the multi-component, multi-target, and multi-pathway characteristics in the treatment of AKI. The result lays a foundation for further study of its specific mechanism.

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