1.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
2.Research progress in anti-tuberculosis drug targets and novel therapeutic strategies
Yang ZHANG ; Ming-rui SUN ; Xiao-tian LI ; Ren FANG ; Jia-yin XING ; Ning-ning SONG
Chinese Journal of Zoonoses 2025;41(4):351-357
Tuberculosis(TB),a chronic infectious disease caused by infection with the Mycobacterium tuberculosis complex(MTBC),has re-emerged as the leading cause of death from a single infectious agent worldwide.Because of widespread use and mis-use of anti-tuberculosis drugs,the emergence of multidrug-resistant TB(MDR-TB)and extensively drug-resistant TB(XDR-TB)is increasing,thus posing a serious threat to global health.The current problem of drug resistance is a major prevention and treatment challenge;therefore,the search for new drug targets is urgently needed.In recent years,substantial progress has been made in re-search on anti-tuberculosis drug targets and novel therapeutic strategies.Herein,we summarize recent research progress in anti-tuberculosis drug targets,primarily cell wall synthesis,nucleic acid replication and transcription,and energy metabolism.We also provide an overview of research progress regarding two novel therapeutic strategies,to provide a theoretical basis and research ideas for the development of new clinical drugs.
3.Mechanical thrombectomy vs.catheter-directed thrombolysis for acute inferior vena cava thrombosis:a prospective randomized trial
Lin MA ; Xuan TIAN ; Han ZHENG ; Jianlong LIU ; Yuedi YIN ; Lingyan WANG ; Jinyong LI ; Xiao LIU ; Mi ZHOU ; Run HUA
Chinese Journal of General Surgery 2025;34(6):1178-1187
Background and Aims:Acute inferior vena cava thrombosis(IVCT)commonly occurs secondary to inferior vena cava filter(VCF)implantation.If not promptly treated,it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval.Percutaneous mechanical thrombectomy(PMT)and catheter-directed thrombolysis(CDT)are currently the main interventional treatments for IVCT,but comparative studies evaluating their efficacy and safety remain limited.This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates,thereby providing evidence-based guidance for clinical decision-making.Methods:From January 2022 to December 2024,patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery,Beijing Jishuitan Hospital,Capital Medical University.Patients were randomly assigned to either the CDT group(n=46)or the PMT group(n=48)according to the interventional procedure used.The two groups were compared in terms of filter retrieval rates,thrombus clearance outcomes,operative time,thrombolytic drug dosage,and incidence of complications.Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results:A total of 94 patients were enrolled,with 46 in the CDT group and 48 in the PMT group.Compared to the CDT group,the PMT group demonstrated a significantly higher primary filter retrieval rate(77.1%vs.43.5%),grade Ⅲ thrombus clearance rate(70.8%vs.37.0%),and better postoperative thrombus scores.Additionally,the PMT group required lower urokinase doses and shorter thrombolysis duration(all P<0.05).The overall filter retrieval rate and 3-month IVC patency were similar between groups,both exceeding 93%.Regarding safety,the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury,while vagal reflex symptoms were more frequent in the PMT group.Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group(OR=190.773,P<0.05).Conclusion:Compared to CDT,AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage.However,attention should be paid to the increased risk of vagal reflex symptoms.There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency.The choice of intervention should be based on the patient's condition,timing of filter retrieval,and individualized clinical considerations.
4.Analysis of factors influencing prolonged length of hospital stay after transjugular intrahepatic portosystemic shunt and construction of its prediction model
Zhaorong WU ; Qian WANG ; Qin YIN ; Tian TIAN ; Han SONG ; Jiangqiang XIAO ; Wen LI
Journal of Interventional Radiology 2025;34(4):418-424
Objective To investigate the risk factors influencing the prolonged length of hospital stay after transjugular intrahepatic portosystemic shunt(TIPS)in patients with ruptured esophagogastric variceal bleeding(EGVB)and to construct a risk prediction model.Methods The clinical data of 215 patients with EGVB,who received TIPS at a certain grade ⅢA hospital in Nanjing of China from January 1,2020 to January 30,2023,were retrospectively analyzed.According to whether the postoperative hospitalization stay was prolonged or not,the patients were divided into prolonged group(n=67)and normal group(n=148).Multivariate logistic regression analysis was sued to analyze the independent risk factors for prolonged postoperative hospitalization stay,and the risk factors were used as predictors for constructing the nomogram model.Results Multivariate logistic regression analysis showed that history of splenectomy,early TIPS performance,NRS 2002 Nutritional Risk Screening Score ≥3 points,and Barthel index score≤40 points were the independent risk factors for prolonged postoperative hospitalization stay in patients with cirrhotic EGVB after receiving TIPS(P<0.05).The area under receiver operating characteristic(ROC)curve of the model constructed on the basis of independent risk factors was 0.743,which was higher than that of early TIPS performance,history of splenectomy,NRS 2002 score,and Barthel index score.The Hosmer-Lemeshow test obtained P=0.723,indicating that this model had a good fit degree.Conclusion The prediction model established in this study can be used for cirrhotic EGVB patients to predict the risk of prolonged postoperative hospitalization stay,and this model has good discrimination and calibration,besides,it can bring some clinical benefits to patients.
5.A Novel Model of Traumatic Optic Neuropathy Under Direct Vision Through the Anterior Orbital Approach in Non-human Primates.
Zhi-Qiang XIAO ; Xiu HAN ; Xin REN ; Zeng-Qiang WANG ; Si-Qi CHEN ; Qiao-Feng ZHU ; Hai-Yang CHENG ; Yin-Tian LI ; Dan LIANG ; Xuan-Wei LIANG ; Ying XU ; Hui YANG
Neuroscience Bulletin 2025;41(5):911-916
6.Mechanical thrombectomy vs.catheter-directed thrombolysis for acute inferior vena cava thrombosis:a prospective randomized trial
Lin MA ; Xuan TIAN ; Han ZHENG ; Jianlong LIU ; Yuedi YIN ; Lingyan WANG ; Jinyong LI ; Xiao LIU ; Mi ZHOU ; Run HUA
Chinese Journal of General Surgery 2025;34(6):1178-1187
Background and Aims:Acute inferior vena cava thrombosis(IVCT)commonly occurs secondary to inferior vena cava filter(VCF)implantation.If not promptly treated,it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval.Percutaneous mechanical thrombectomy(PMT)and catheter-directed thrombolysis(CDT)are currently the main interventional treatments for IVCT,but comparative studies evaluating their efficacy and safety remain limited.This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates,thereby providing evidence-based guidance for clinical decision-making.Methods:From January 2022 to December 2024,patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery,Beijing Jishuitan Hospital,Capital Medical University.Patients were randomly assigned to either the CDT group(n=46)or the PMT group(n=48)according to the interventional procedure used.The two groups were compared in terms of filter retrieval rates,thrombus clearance outcomes,operative time,thrombolytic drug dosage,and incidence of complications.Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results:A total of 94 patients were enrolled,with 46 in the CDT group and 48 in the PMT group.Compared to the CDT group,the PMT group demonstrated a significantly higher primary filter retrieval rate(77.1%vs.43.5%),grade Ⅲ thrombus clearance rate(70.8%vs.37.0%),and better postoperative thrombus scores.Additionally,the PMT group required lower urokinase doses and shorter thrombolysis duration(all P<0.05).The overall filter retrieval rate and 3-month IVC patency were similar between groups,both exceeding 93%.Regarding safety,the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury,while vagal reflex symptoms were more frequent in the PMT group.Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group(OR=190.773,P<0.05).Conclusion:Compared to CDT,AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage.However,attention should be paid to the increased risk of vagal reflex symptoms.There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency.The choice of intervention should be based on the patient's condition,timing of filter retrieval,and individualized clinical considerations.
7.National bloodstream infection bacterial resistance surveillance report 2023: Gram-positive bacteria
Chaoqun YING ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(2):118-132
Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute(CLSI). Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus( n=1 544,35.2%),coagulase-negative Staphylococci( n=1 441,32.9%), Enterococcus faecium( n=574,13.1%), Enterococcus faecalis( n=385,8.8%),and α-hemolytic Streptococci( n=187,4.3%). The prevalence of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)was 26.2%(405/1 544)and 69.8%(1 006/1 441),respectively. Notably,all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility(>97.0%)to cephalobiol,rifampicin,trimethoprim-sulfamethoxazole,linezolid,minocycline,tigecycline,and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium(resistance to vancomycin and teicoplanin:both 1.7%)compared to Enterococcus faecalis(both 0.3%). The detection rates of MRSA and MRCNS exhibited significant regional variations across the country( χ2=17.674 and 148.650,respectively,both P<0.001). No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA( χ2=14.111, P<0.001)and MRCNS( χ2=4.828, P=0.028)in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA( χ2=18.986, P<0.001)and MRCNS( χ2=4.477, P=0.034)in less developed regions(per capita GDP
8.National bloodstream infection bacterial resistance surveillance report (2023) : Gram-negative bacteria
Jinru JI ; Zhiying LIU ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(1):47-62
Objective:To report the results of bacterial resistant investigation collaborative system(BRICS)on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023,and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period,11 492 strains of Gram-negative bacteria were collected from 60 hospitals,of which 10 098(87.9%)were Enterobacterales and 1 394(12.1%)were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli(50.0%), Klebsiella pneumoniae(26.1%), Pseudomonas aeruginosa(5.1%), Acinetobacter baumannii complex(5.0%)and Enterobacter cloacae complex(4.1%). The ESBL-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus mirablilis were 46.8%(2 685/5 741),18.3%(549/2 999)and 44.0%(77/175),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(76/5 741)and 15.0%(450/2 999);32.9%(25/76)and 78.0%(351/450)of CREC and CRKP were sensitive to ceftazidime/avibactam combination,respectively. 94.7%(72/76)and 90.2%(406/450)of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore,57.9%(44/76)and 79.1%(356/450)were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 64.6%(370/573),while more than 80.0% of CRAB complex was sensitive to tigecycline,eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 17.0%(99/581). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China,with statistically significant differences in the prevalence of CREC,CRKP,CRPA and CRAB complex( χ2=10.6,28.6,10.8 and 19.3, P<0.05). The prevalence of ESBL-producing Escherichia coli, CREC,CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals( χ2=12.5,9.8,12.7 and 57.8,all P<0.01). Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China,and Escherichia coli is ranked in the top,while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend,CREC infecton maintains a low prevalence level,and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.
9.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
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Electroacupuncture
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Male
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Magnetic Resonance Imaging
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Depression/diagnostic imaging*
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Mice, Inbred C57BL
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Brain/diagnostic imaging*
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Disease Models, Animal
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Mice
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Pain/diagnostic imaging*
;
Acupuncture Points
10.Network pharmacology, molecular docking, and animal experiments reveal mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children.
Yong-Kai YIN ; Chang-Miao NIU ; Li-Ting LIANG ; Mo DAN ; Tian-Qi GAO ; Yan-Hong QIN ; Xiao-Ning YAN
China Journal of Chinese Materia Medica 2025;50(1):228-238
Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Molecular Docking Simulation
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Adipose Tissue/immunology*
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Mice
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Male
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Humans
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Network Pharmacology
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Macrophages/immunology*
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Mice, Inbred C57BL
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Child
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Protein Interaction Maps/drug effects*
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Obesity/genetics*
;
Inflammation/drug therapy*


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