1.Identification of GSK3 family and regulatory effects of brassinolide on growth and development of Nardostachys jatamansi.
Yu-Yan LEI ; Zheng MA ; Jing WEI ; Wen-Bing LI ; Ying LI ; Zheng-Ming YANG ; Shao-Shan ZHANG ; Jing-Qiu FENG ; Hua-Chun SHENG ; Yuan LIU
China Journal of Chinese Materia Medica 2025;50(2):395-403
This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism*
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Steroids, Heterocyclic/metabolism*
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Gene Expression Regulation, Plant/drug effects*
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Plant Proteins/metabolism*
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Phylogeny
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Nardostachys/metabolism*
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Plant Growth Regulators/pharmacology*
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Plant Roots/drug effects*
2.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
3.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
OBJECTIVE:
Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:
A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:
Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION
Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology*
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Animals
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MicroRNAs/genetics*
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Lipopolysaccharides
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Ferroptosis/drug effects*
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Mice
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Myocytes, Cardiac/metabolism*
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Signal Transduction/drug effects*
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Rats
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Male
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Mice, Inbred C57BL
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Cardiomyopathies/etiology*
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Cell Line
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Sepsis/complications*
4.Determination of Isobutyl Chloroformate Residue in Agatroban by Derivatization-Gas Chromatography-Mass Spectrometry
Chong QIAN ; Bo-Kai MA ; Chuang NIU ; Shan-Shan LIU ; Wen-Wen HUANG ; Xin-Lei GOU ; Wei WANG ; Mei ZHANG ; Xue-Li CAO
Chinese Journal of Analytical Chemistry 2024;52(1):113-120
A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.
5.Clinical observation of goserelin combined with estradiol valerate in the treatment of endometriosis in patients of childbearing age after laparoscopic surgery
Huiling WANG ; Ning MA ; Lei QIAO ; Jun YANG ; Zhengfang WEN
China Pharmacy 2024;35(14):1748-1752
OBJECTIVE To observe the efficacy and safety of goserelin combined with estradiol valerate in the treatment of endometriosis (EMs) in patients of childbearing age after laparoscopic surgery. METHODS The clinical data of 144 patients with EMs of childbearing age who underwent laparoscopic surgery in our hospital from January 2020 to December 2022 were collected retrospectively, and those patients were divided into control group (70 cases) and combination group (74 cases) based on different postoperative medication regimens. Control group was given Acetate goserelin sustained-release implant on the 1st to 5th day of their first menstrual cycle after laparoscopic surgery, while combination group was additionally given Estradiol valerate tablets on the basis of control group. The short-term and long-term efficacy of 2 groups were observed; preoperative and postoperative pain scores, ovarian reserve function, and the incidence of adverse reactions were all recorded in 2 groups. RESULTS There was no statistically significant difference in short-term total effective rate, 1-year postoperative recurrence rate and the incidence of decreased libido, vaginal dryness, gastrointestinal reactions, rash, or arrhythmia between two groups (P>0.05). The natural pregnancy rate of combination group was significantly higher than control group at 1 year after surgery, while the incidence E-mail:wanghuiling0518@126.com of early miscarriage, hot flashes and sweating, emotional fluctuations, insomnia and fatigue, joint muscle pain, dizziness and headache were significantly lower than control group (P<0.05). However, at 6 months after surgery, pain scores and the levels of anti-Müllerian hormone, follicle stimulating hormone, luteinizing hormone, estradiol of both groups were significantly lower than before surgery in the same group, while the number of antral follicle count was significantly higher than before surgery in the same group; the levels of anti-Müllerian hormone, luteinizing hormone, estradiol, and the number of antral follicles in the combination group were significantly higher than control group, while pain score and follicle stimulating hormone level were significantly lower than control group (P<0.05). CONCLUSIONS The combination of goserelin and estradiol valerate after laparoscopic surgery has a significant therapeutic effect and good safety in the treatment of EMs of childbearing age.
6.Clinical Study on Huangjing Jiangya Decoction in the Treatment of Patients with Hypertension of Qi-Deficiency Type Accom-panied by Insomnia
Wen SHI ; Haijuan MA ; Jintao HE ; Lei DONG ; Yao LIU ; Huiling ZHAO ; Yuan XING
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(11):1256-1262
OBJECTIVE To observe the effect of Huangjing Jiangya Decoction on blood pressure and sleep in patients with hy-pertension of qi-deficiency type accompanied by insomnia.METHODS 73 patients with hypertension of qi-deficiency type accompa-nied by insomnia who met the inclusion criteria were selected and randomly divided into an observation group of 36 cases and a control group of 37 cases.The control group was treated with amlodipine besylate tablets,and the observation group was given Huangjing Jian-gya Decoction oral treatment on the basis of the control group.Both groups were treated continuously for 8 weeks.The changes in TCM syndrome scores,office blood pressure monitoring(OBPM),home blood pressure monitoring(HBPM),24-hour ambulatory blood pressure monitoring(ABPM),Pittsburgh Sleep Quality Index(PSQI)scores and clinical efficacy of the two groups of patients before and after treatment were observed.RESULTS After treatment,the TCM syndrome scores in the observation group were significantly decreased(P<0.05,P<0.01),which were better than the control group(P<0.01);OBPM and HBMP in both groups were signifi-cantly reduced(P<0.05,P<0.01),the observation group was better than the control group(P<0.05,P<0.01);the ABPM of the observation group was significantly reduced(P<0.01),which was better than the control group(P<0.05,P<0.01);the sleep quali-ty,sleep latency,sleep duration,daytime dysfunction score and PSQI total score of the observation group were significantly decreased(P<0.01),which were better than those in the control group(P<0.05,P<0.01);the clinical efficacy of hypertension and insomnia in the observation group was both better than the control group(P<0.01).CONCLUSION Huangjing Jiangya Decoction combined with amlodipine can improve the symptoms of patients with hypertension of qi-deficiency type accompanied by insomnia,lower blood pressure,improve sleep quality,shorten sleep latency,alleviate daytime dysfunction,and has good clinical efficacy.
7.Protective effect of naringin on sepsis-induced acute lung injury in mice
Che LIU ; Yuan MA ; Xu-Peng DONG ; Qian-Wen DUAN ; Jiao LEI ; Yu-Qing MA
The Chinese Journal of Clinical Pharmacology 2024;40(5):693-697
Objective To investigate the effect and mechanism of naringin on acute lung injury(ALI)in septic mice.Methods The acute lung injury mouse model of sepsis was established by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide.The mice were randomly divided into control group(injected with equal amounts of saline and phosphate buffer),model group(mouse model of sepsis acute lung injury),naringin group(50 mg·kg-1 naringin injected intraperitoneally 1 hour prior to lipopolysaccharide modeling)and BzATP group(50 mg·kg-1 naringin+5 mg·kg-1 BzATP injected intraperitoneally 1 hour prior to lipopolysaccharide modeling).After modeling,lung tissues were taken 24 h later,lung coefficients were calculated;lung tissue interleukin(-ILβ-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay;the expression of purinergic 2X7 receptor(P2X7R),nucleotide-binding oligomerization structural domain-like receptor protein 3(NLRP3)and nuclear factor-κB(NF-κB)proteins were detected by Western blotting.Results The lung coefficients in the control,model,naringin and BzATP groups were(6.26±0.31),(9.09±1.02),(7.02±0.45)and(8.79±0.55)mg·g-1;the contents of TNF-α were(56.41±0.35),(174.68±1.58),(85.23±1.68)and(162.97±3.42)pg·mL-1;the contents of IL-1β were(44.18±7.37),(119.91±17.16),(85.41±2.14)and(104.57±3.39)pg·mL-1;the contents of IL-10 were(50.82±2.89),(28.31±1.86),(42.82±1.98)and(25.19±1.69)pg·mL-1;P2X7 protein expression levels were 0.45±0.16,1.33±0.10,0.64±0.09 and 1.05±0.18;NF-κB protein expression levels were 0.38±0.19,1.29±0.09,0.57±0.11 and 0.92±0.07;NLRP3 protein expression levels were 0.72±0.14,1.28±0.23,0.75±0.09 and 1.27±0.23.Compared with the model group in the control group and naringin group,compared with the naringin group in the BzATP group,the differences of the above indexes were statistically significant(P<0.01,P<0.05).Conclusion Naringin attenuates acute lung injury in septic mice by inhibiting the P2X7 receptor-mediated NF-κB/NLRP3 signaling pathway.
8.Therapeutic effects of paeoniflorin on thromboangiitis obliterans model rats by regulating PI3K/AKT/NF-κB signaling pathway
Ya-Na WANG ; Xiao-Lin XU ; Wen-Hua MA ; Luo-Fang CUI ; Li LIU ; Lin-Li XU ; Yan ZHANG ; Xiu-Lei ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):854-858
Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9%NaCl),model group(intraperitoneal injection of 0.9%NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P<0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P<0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P<0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.
9.Effects of circular RNA_0054633 on hydrogen peroxide-induced oxidative damage in myocardial cells
Yan-Wei WANG ; Bian-Wen WU ; Lei CAO ; Jie MA ; Ya-Li FENG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1560-1564
Objective To investigate whether circular RNA(circRNA)circ_0054633 targets microRNA-375(miR-375)to regulate the oxidative damage of cardiomyocytes induced by hydrogen peroxide(H2O2).Methods H9C2 cardiomyocytes were divided into control group(normal culture without any treatment),hydrogen peroxide(H2 O2)group(150 μmol·L-1 H2 O2 treated cardiomyocytes for 6 h),H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+miR-375 group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group(cardiomyocytes were transfected with si-NC,si-circ_0054633,miR-NC,miR-375 mimics,si-circ_0054633+anti-miR-NC,si-circ_0054633+anti-miR-375,respectively;24 h after transfection,cardiomyocytes were treated with 150 μmol·L-1 H2O for 6 h).Real-time fluorescence quantitative polymerase chain reaction was used to determine the expression of miR-375,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)were determined by kit,apoptosis was determined by flow cytometry.Results The expression levels of miR-375 in cardiomyocytes of control group,H2O2 group,H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group were 1.00±0.00,0.42±0.05,0.40±0.06,0.69±0.08,1.00±0.00,3.41±0.28,1.00±0.00 and 0.26±0.02,respectively;MDA contents were(3.19±0.32),(13.46±1.27),(15.39±1.04),(5.26±0.51),(16.05±1.36),(9.18±0.85),(4.89±0.44)and(10.05±0.92)nmol·L-1,respectively;SOD activities were(64.69±5.81),(18.23±1.33),(17.07±1.41),(55.74±5.13),(17.12±1.64),(47.66±4.59),(56.77±4.71)and(27.95±2.47)U·mL-1,respectively;the apoptosis rates were(6.21±0.59)%,(29.22±2.19)%,(30.94±2.85)%,(10.05±0.92)%,(31.14±2.83)%,(13.74±1.24)%,(10.39±0.88)%and(21.31±1.92)%,respectively.The above indexes of H2O2 group were compared with the control group,the above indexes of H2O2+si-circ_0054633 group was compared with the H2O2+si-NC group,the above indexes of H2O2+miR-375 group was compared with the H2O2+miR-NC group,the above indexes of H2O2+si-circ_0054633+anti-miR-375 group were compared with H2O2+si-circ_0054633+anti-miR-NC group,the differences were statistically significant(all P<0.05).Conclusion Interfering with the expression of circ_0054633 can reduce the oxidative stress and apoptosis of cardiomyocytes induced by hydrogen peroxide by targeting miR-375,thereby protecting cardiomyocytes from oxidative damage.
10.Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis
Fei Wen GU ; Xia SHI ; Xin MA ; Lei Jun YU ; Chuan Jin XU ; Cheng Cheng QIAN ; Dong Zhi HU ; Hui ZHANG
Biomedical and Environmental Sciences 2024;37(2):170-177
Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

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